http://www.sciencedaily.com/releases/2009/12/091228171730.htm..Melanoma..Jim Breitfeller

http://www.sciencedaily.com/releases/2009/12/091228171730.htm

Take Care,

Jimmy B

Adoptive Immunotherapy of Cancer using CD4+ T cells.Melanoma..Jim Breitfeller

Adoptive immunotherapy of cancer using CD4+ T cells
Pawel Muranski and Nicholas P Restifo

I have been in contact with Dr. Restifo and he was so generous to share his Research papers with us.

As I started to read this one, I thought it would be better to put it in the shared file on Melanoma Missionary. I think it may interest many patients.

Adoptive immunotherapy of cancer using CD4+ T cells




Hi Jim,


Thanks for the update of your analysis of the work. Have you had any luck posting this on the Wiki site? Here’s a stack of some of our recent papers. Almost all of our papers before 2008 are available on www.pubmed.org.

Best regards,

Nick


Nicholas P Restifo, MD

Principal Investigator

National Cancer Institute

Abstract:
CD4+ T cells are central to the function of the immune system
but their role in tumor immunity remains underappreciated. It is
becoming clear that there is an enormous diversity of CD4+
T cell polarization patterns including Th1, Th2, Th17, and
regulatory T cells (Tregs). These functionally divergent T cell
subsets can have opposing effects — they can trigger tumor
rejection or inhibit treatment after adoptive cell transfer. Some
polarized CD4+ cells have plasticity, and their phenotypes and
functions can evolve in vivo. Recent advances in understanding
of polarization and differentiation of lymphocytes, as well as
some intriguing developments in the clinic, indicate that the use
of CD4+ T cell subsets in the immunotherapy of cancer has
unrealized potential.

Take care

Jimmy B
Melanoma_Missionary


"Today might be the worst day of your life...but tomorrow could be the best. You just have to get there."
~Unknown~




border="0" alt="For the Warriors">






Take Care,

Jimmy B

CTLA 4 Success Rate melanoma trials.. Jim Breitfeller

The most interesting data was on ipiliumumab (abstract #9033), which looked at the effect of the agent on 18 and 24 month survival from 3 phase II trials dosed at 10mg/kg every 3 weeks (plus maintenance therapy Q12W from week 24 in appropriate patients) in advanced melanoma, where survival outcomes are usually poor. Ipilumumab is a fully humanised monoclonal antibody that targets T-lymphocyte antigen 4 (CTLA-4).

The 3 studies summarised were CA184-008, CA184-022, CA184-007.

The results clearly showed that:

- 12 month survival rates were >47%
- 18 month survival rates were >34%
- 24 month survival rates were >30%

"For previously treated patients, 24 month survival rates ranged from 24% to 33%.
Long term survivors included patients with progressive disease according to WHO criteria.
These results are promising but caution must be extended because a significant number of patients were lost to follow-up, which may reduce the reliability of the results. Ongoing biomarker studies are looking at predicting which patients are most likely to benefit from ipilumumab therapy.

Ipiliumumab


What did we learn from these trials? Well, there is an urgent need to define optimal endpoints for melanoma clinical trials in terms of response rate, PFS, OS and survival at 12 months. It is interesting that over the past 10 years the majority of abstracts have hyped the results in this disease as 'promising' or 'clinically active' regimens and yet very little in the way of new therapies have actually been approved by the FDA. Based on these data, I suspect it will still be a little while before we see some solid phase III data in malignant melanoma."









Take Care,

Jimmy B

Identification and Validation of Combination Therapies for Melanomas..Jim Breitfeller

FW: Identification and Validation of Combination Therapies for Melanomas

I got my Christmas Wish!!!!!!!!!!!!!!!!!

-----Original Message-----

From: Slingluff, Craig *HS [mailto:CLS8H@hscmail.mcc.virginia.edu]

Sent: Thursday, December 24, 2009 11:51 AM

To: dbreitfe@rochester.rr.com

Cc: Weber, Michael J - Cancer Center *HS; Engelhard, Victor H

Subject: RE: Identification and Validation of Combination Therapies for Melanomas

Dear Mr. Breitfeller,

Mike Weber was kind to forward your paper and email. It appears that you have a very good sense of, and interest in, the immune response to melanoma and to cancer in general. I believe you are right that timing of the various components of the immune response, especially with combination therapies, is important, just as it is in the orchestration of a beautiful symphony. I wish you success in your treatments and in your work to understand and to explain the immune response to cancer.

Craig Slingluff

Craig L. Slingluff, Jr. M.D.

Joseph Helms Farrow Professor of Surgery

Division of Surgical Oncology

Vice-Chair for Research

Director, Human Immune Therapy Center

University of Virginia

Charlottesville, VA 22908

cls8h@virginia.edu

434-924-1730

http://www.box.net/shared/kjgr6dkztj
Melanoma and the Magic Bullet (monoclonal Antibodies)



Michael J. Weber, Ph.D.
Professor of Microbiology
Research Interests:
Signal Transducing Kinases in Cancer





Signal transduction by serine/threonine kinases
The Weber laboratory utilizes tools of cell biology, protein chemistry and molecular biology to understand how signal transduction pathways control cell growth and apoptosis and how these controls are altered in cancer. A major focus of this research is on the MAP Kinase cascade, a ubiquitous signaling pathway that generates specific biological outcomes dependent on biological context. Recent findings of the lab have demonstrated an important role for "scaffolding proteins" that assemble components of the signaling cascades. They recently discovered the MORG1 scaffold protein (MAP Kinase Organizer) that regulates responses to LPA but not EGF. Signaling scaffolds can control the location, regulation, timing, substrates, biological functions, and suitability for therapeutic intervention of a signaling pathway. This research made use of the Biostatistics Core, to help evaluate multi-factorial responses to mitogens, and the Mass Spec and DNA cores for molecular and proteomic analysis.

The lab pioneered the use of phosphorylation-site specific antibodies to probe archival paraffin-embedded pathology specimens, and discovered that the MAP Kinase cascade was activated in prostate cancer. Activation of this pathway is sufficient for and can be necessary for progression of prostate cancer to an androgen-independent disease. Therefore the Ras-MAP Kinase pathway is an attractive target for therapy of advanced prostate cancer.

Current research aims to determine how to select combinations of therapies in cancer treatment.


Merry Christmas

Jimmy Breitfeller






Take Care,

Jimmy B

It's Christmas.. SentoClone may be Coming to Town!!Melanoma..Jim Breitfeller

It's Christmas.. SentoClone may be Coming to Town!!!!

SentoClone AB is a Swedish biotech company developing a patented immunotherapy for cancer treatment based on autologous T lymphocytes extracted from the sentinel node, the first tumor draining lymph node. The sentinel node is resected in conjunction with tumor reducing surgery.
The extracted lymphocytes are cultivated in vitro and activated. The activated lymphocytes multiply and are given back to the patient after 4 to 6 weeks by a simple transfusion.
So far, more than 110 patients have been treated. As the therapy is based on autologous cells, significant side effects are not expected and have not been seen.
A randomised controlled phase II study in advanced malignant melanoma has recently been started and further studies are planned in other indications.





Merry Christmas!!!!!!

Jimmy B


Today might be the worst day of your life...but tomorrow could be the best. You just have to get there."
~Unknown~

Bristol-Meyer Squibb the New Dr. Kevorkian of the Decade?Melanoma..Jim Breitfeller

Is Bristol-Meyer Squibb the New Dr. Kevorkian of the Decade?

• Mislead the public/Government about the Ipilimumab Shortage
• Stopped the compassionate drug use on 9/12/2008
• Continued to create/open clinical trials with Ipilimumab
• Increased their stock dividend as of February 2010
• Continuously turn away Melanoma patients that did not qualify for their trials

As a Melanoma Patient and a survivor, I believe BMS is the New Dr. Kevorkian.
They are killing cancer patients that have no other alternative and Anti-CTLA-4 blockage was their last hope.
“Scientists have discovered that an important mechanism for down regulation is mediated by a molecule called CTLA-4. The T cells are initially activated by other immune cells, called dendritic cells, that display the foreign, or cancerous, antigens to the T cells and instruct them to be active. After this initial activation, CTLA-4 appears on the surface of the T cells, and when CTLA-4 interacts with the dendritic cells, the next set of signals are to turn the response down, or even off. CTLA-4 is part of a regulatory mechanism that normally protects the body from immune overreactions, but when it is expressed in the presence of mutant cancer cells the result is tumor evasion of the immune response. Ipilimumab is an antibody that blocks CTLA-4, releasing this safety brake, and allowing the immune response to have a stronger anti-tumor effect.”

Source: Oregon Health and Science University

With Bristol-Meyer Squibb not allowing compassionate drug use, they are invoking a death sentence on the cancer patient. Since Pfizer pulled out of this therapy due to the fact they wanted the drug as a monotherapy when the scientific data suggests that a combination of this drug would have better results. So BMS now has a monopoly on this drug and will be able to charge a great deal for it even though it is made in thousands of units per batch. When will the FDA coming in and do what is ethical for the country?


We cannot let a deceitful and greedy company control our destiny.


“In our daily life, we encounter people/companies who are deceitful, intent only on satisfying their own needs. There is so much anger, distrust, greed, and pettiness that we are losing our capacity to work well together to do what is ethically right.”
Jimmy B


Take Care,

Jimmy B

Bristol Meyer Squibb."When you marry the devil's daughter don't be surprised when your father-in-law comes to visit."Melanoma.. jim breitfeller

Mead Johnson Loses $13.5 Million Lawsuit to PBM Products


December 2, 2009 11:23 AM EST

PBM Products, LLC, has received a favorable jury verdict and a $13.5 million damages award in its false advertising lawsuit against Mead Johnson & Co., the operating subsidiary of Mead Johnson Nutrition Company (NYSE: MJN), the makers of the national-brand Enfamil(R) LIPIL(R) Infant Formula. Mead Johnson is 83 percent-owned by Bristol-Myers Squibb (NYSE: BMY).

PBM's lawsuit claimed that Mead Johnson engaged in false and misleading campaigns against PBM's competing store-brand of infant formulas, suggesting they do not provide the same nutrition as Mead Johnson's brands. PBM's store-brand infant formulas cost up to 50 percent less than Enfamil(R) LIPIL(R). The $13.5 million in damages awarded by the jury in the United States District Court for the Eastern District of Virginia is one of the largest damages awards ever for a false advertising case.

(Source PBM Products)

If BMS is willing to mislead on baby formula, Can you believe that they was ever a Ipilimumab Shortage?

All smoke and mirrors!!!!!!!

I see a pattern of misleading the public over the last decade from Bristol-Meyer Squibb.


Take Care,

Jimmy B

Patient’s own infection-fighting T cells put late-stage melanoma into long-term remission..Melanoma Jim Breitfeller

Patient’s own infection-fighting T cells put late-stage melanoma into long-term remission

Researchers identify the first successful end of a human patient’s cloned infection-fighting T cells as the sole psychotherapy to snap an advanced through-and-through-tumor cancer into long-term exemption. A body led by Cassian Yee, M.D., an associate member of the Clinical Research Division at Fred Hutchinson Cancer Research Center, reports these findings in the June 19 issue of the New England Journal of Medicine.


Yee and colleagues removed CD4+ T cells, a type of white blood cell, from a 52-year-old man whose Stage 4 melanoma had spread to a groin lymph node and to a lung. T cells specific to targeting the melanoma were then expanded vastly in the laboratory using modifications to existing methods. The lab-grown cells were then infused into the patient with no additional pre- or post-conditioning therapies, such as growth-factor or cytokine treatment. Two months later, PET and CT scans revealed no tumors. The patient remained disease free two years later, when he was last checked.

“We were surprised by the anti-tumor effect of these CD4 T cells and its duration of response,” Yee said. “For this patient we were successful, but we would need to confirm the effectiveness of therapy in a larger study.”

Yee cautioned that these results, presented in the journal’s “Brief Report” section, represent only one patient with a specific type of immune system whose tumor cells expressed a specific antigen. More studies are needed to confirm the effectiveness of the experimental T-cell therapy. If proven successful in more patients, Yee predicted this therapy could be used for the 25 percent of all late-stage melanoma patients who have the same immune-system type and tumor antigen.

Using a patient’s own immune system to combat cancer, called immunotherapy, is a growing area of research that aims to develop less-toxic cancer treatments than standard chemotherapy and radiation.

The patient in the journal report was one of nine patients with metastatic melanoma who were being treated in a recently completed clinical trial to test dose- escalation of autologous CD4+ T cells. Earlier studies performed by Yee used CD8+ T cells, which do not persist in the body without the support of CD4+ T cells or growth factors such as interleukin 2. Yee and colleagues theorized that infusion of a massive dose of CD4+ T cells would persist longer in the body because they make their own growth factor, interleukin 2, while stimulating the anti-tumor effect of the patient’s existing CD8+ T cells. However, until recently there was no feasible way to isolate and expand anti-tumor CD4+ T cells in the lab.

The researchers were successful in all of these areas. The patient received a dose of 5 billion cloned CD4+ T cells with specificity for the melanoma-associated NY-ESO-1 antigen. The cells persisted for at least 80 days in the patient’s body. And, even though only 50 percent to 75 percent of the patient’s tumor cells expressed the NY-ESO-1 antigen, the entire tumor regressed following the infusion. The scientists postulated that the patient’s immune response was broadened to other antigens expressed by the tumor cells. Follow-up tests showed T-cell responses to two additional tumor antigens, MAGE-3 and MART-1.

Researchers in Yee’s lab, the University of Washington School of Medicine and the Ludwig Institute for Cancer Research in New York collaborated on the research. The Burroughs-Wellcome Foundation, Damon Runyon Cancer Research Foundation, Edson Foundation and National Cancer Institute funded the study.

http://www.fhcrc.org

This was written by collegeseattle


"Today might be the worst day of your life...but tomorrow could be the best. You just have to get there."
~Unknown~




Take Care,

Jimmy B

Bristol-Meyer Squibb.."When you marry the devil's daughter don't be surprised when your father-in-law comes to visit."Melanoma.. Jim Breitfeller

Monday, May 18, 2009
Quote of the week - and It's only Monday morning!

"When you marry the devil's daughter don't be surprised when your father-in-law comes to visit."

Corey Nahman writes:

A Celebrity Patient's Backing Turns Sour for Drug Company … wasn't the truth, he says now. Within weeks of taking Abilify, Mr. Behrman says he felt stiffness and agitation in his legs. He says Abilify clouded his thinking. He now says the drug made him feel worse than any treatment he has tried…[Wall Street Journal]

Editor's Note: Sequence of events: (A) Bristol hires author/bipolar patient to tell the world how great Abilify is, pays him $10K per day in speaking fees and he tells everyone it is the best thing since sliced bread.(B) His contract is over and he demands $7.5 million to renew; BMS tells him to shove it.(C) Now he's going around saying that he lied all along and Abilify hade him feel like crap.

Bottom Line: When you marry the devil's daughter don't be surprised when your father-in-law comes to visit.

This happened in 2009. BMS still has not changes it's way of doing business. It is all about the bottom-line and how to make a profit.

Now think about the Ipilimumab Shortage. Go to the Clininal Trial website and see all the trials started after the shortage/ stoppage of the the compassionate drug use (Ipilimumab).

This is not rocket science

We been had!!!!
Mislead!!!!!

Patients have died due to the fact they did not have access to Ipilimumab.

BMS only cares about the bottom-line. What about what is ethically right?

They are the Tiger Woods of the pharma companies.We should boycott them.








Take Care,

Jimmy B

2009 Sustainability Reporting of the World's Largest Pharmaceutical Companies (BMS)..What about Ethics??? Melanoma ..Jim Breitfeller

Dr. Morhardt,

While reading the Scores

2009 Sustainability Reporting of the World's Largest

Pharmaceutical Companies

A benchmarking tool for online sustainability reporting

Roberts Environmental Center

Source: http://www.roberts.cmc.edu/PSI/PDF/Pharmaceuticals2009.pdf

I have some comments:

While base on your environmental standards Bristol-Meyers Squibb is worthy of an A+, their Ethical conduct should be also taken into account. As a patient of stage IV Melanoma Cancer, I saw firsthand what BMS is all about. It is greed and the bottom line and the “string of Pearls”. They chose to close the compassionate drug use (Ipilimumab). They told the public and the Government that they were having trouble producing the drug, but proceeded to startup new Clinical trials with the drug after they stopped compassionate drug use. How ethical is that? They even went as far to respond to a patient’s family with this response;” Jimmy, remember what the BMS "doctor" told me "Mrs. Lawrence, you will get the drug for your husband when we can charge for it."



BMS is only looking out for their bottom-line and to hell with patients.

So with this information, BMS in my opinion is only worth a C- to a D+, not an A+.

You can’t just use what they say on their website. You need to do real research. The information on their website is skewed in the drug companies favor.



Best regards,



Jim Breitfeller Patient/Survivor/Researcher of Stage IV Melanoma



http://melanomamissionary.blogspot.com/



Take Care,

Jimmy B

In this Holiday Season there is a Scrooge (Bristol Meyer Squibb) among us!! Melanoma..Jim Breitfeller

In this Holiday Season there is a Scrooge among us. It is the Bristol-Meyer Squibb. In September of 2008 they stopped compassionate drug use (Ipilimumab) because they claimed that they were having trouble producing it. It has come to light that their major intension was to stop giving it away until they could get paid for it. The Shortage was a Magic act. Now it’s there and now it’s not.

To make matters worse, The FDA was contacted and never really looked into the Shortage. Did they turn blind eye or are they short staffed?

I have reason to believe Bristol-Meyer Squibb is the poster boy for Scrooge this Holiday Season In their Company Documents they say:

“What sets us apart? We believe it's our commitment to patients with serious diseases, our focus on finding innovative medicines that combat those diseases, and our dedication to extending and enhancing human life.”
Bristol-Meyer Squibb is committed to their bottom line. They are the Scrooge of the pharmaceutical Industry in my opinion. They all do it, just not as publicly as Bristol-Meyer Squibb.


The company should be investigated on their ethics.


1. They mislead Government officials, the truth about the shortage?
2. They added new Clinical Trials after they stopped Compassionate Drug Use
3. They mislead the general public (The Melanoma Patients)
4. They went so far to amend their Compassionate use protocol to read “the study will be closed to enrollment upon market availability and then need to switch to commercial supply.”
5. Jimmy, remember what the BMS "doctor" told me "Mrs., you will get the drug for your husband when we can charge for it."

This all comes down to Ethics. Doing what is right.

I say to Bristol-Meyer Squibb

“BAH HUM BUG!!!!!”



Please sign the E-Petition at Melanoma Missionary
Your Life may depend on it



Take Care,

Jimmy B

GM-CSF-based Second-generation Oncolytic Herpesvirus Vaccine Promising for Melanoma..Jim Breitfeller

GM-CSF-based Second-generation Oncolytic Herpesvirus Vaccine Promising for Melanoma

Researchers involved in an international multicenter clinical Phase II trial have reported a 26% response rate for patients with metastatic melanoma treated with a second-generation granulocyte-macrophage colony-stimulating factor (GM-CSF) oncolytic herpes simplex virus (HSV) vaccine. The details of this study were published in the December 1, 2009 issue of the Journal of Clinical Oncology.[1]

Melanoma is considered an immune responsive cancer. A small fraction of patients with metastatic disease respond to a variety of immune therapies including: Proleukin® (interleukin-2), lymphokine activated killer (LAK) cells, tumor infiltrating lymphocytes (TIL), and genetically manipulated T-cells. In addition, there have been many attempts to develop a successful vaccine.

A previous Phase I study of this second-generation oncolytic HSV expressing GM-CSF was carried out in patients with a variety of solid tumors. In this study the vaccine was called OncoVEX-GM-CSF and is made by BioVex.[2] This study established a safe dose, and responses were observed in patients with melanoma and other solid tumors.

The current study evaluated the same vaccine, which is called JS1/34.5/47-/GM-CSF, for the treatment of 50 patients with metastatic melanoma. Seventy-five percent of patients in this study had failed one or more systemic therapies. Vaccine was injected into tumor nodules every two weeks for up to 24 treatments, and some patients who responded or were stable were then treated on an extended protocol. These authors made the following observations:

The overall response rate was 26%.
Eight patients (16%) had a complete response.
Five patients (10%) had a partial response.
Responses occurred in injected and distant sites.
10 patients (20%) had stable disease for more than three months.
92% of responses were maintained for 7-31 months.
Two additional patients had a complete response after surgery.
Two additional patients with an initial partial response or stable disease achieved a complete response after 24 months of further vaccination.
Overall survival at one year was 58% and 52% at two years.
Comments: These are the best results achieved to date for any vaccine for melanoma. This study will by followed up by a Phase III study to confirm these results.

References:



--------------------------------------------------------------------------------

[1] Senzer JJ, Kaufman HL, Amatruda T, et al. Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. Journal of Clinical Oncology. 2009;27:5763-5771.

[2] Hu JC, Coffin RS, Davis CJ, et al: A phase I study of OncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor. Clin Cancer Res. 12:6737–6747, 2006.

Source:http://professional.cancerconsultants.com/oncology_main_news.aspx?id=44340



Take Care,

Jimmy B

Bristol-Meyer Squibb and Responsibility..Melanoma ..Jim Breitfeller

Bristol-Meyer Squibb and Responsibility

“We take our responsibilities in the world seriously and always strive to do what is right. We do this for our customers, for our employees, for the environment, for our families and friends, and, for the communities in which we operate.”

~Bristol-Meyer Squibb ~


“To offset the approaching patent “cliff,” as the industry calls it, Bristol decided in 2007 on a twin strategy of cost-cutting and strategic acquisitions. The company reported productivity savings of $1.2 billion in 2008, largely through staff cuts and the shuttering of manufacturing plants. It plans further cuts and savings totaling $1.3 billion by 2012.”

This included shuttering down the Compassionate Care Use of Ipilimumab on 8-12-2008. I believe there was no shortage. They took the opportunity to save on the bottom line instead of saving some Melanoma Patients. They seem not care about the patients as much as their bottom line. They say the take their responsibilities in the world seriously.
PROVE IT. Return the compassionate drug to the patients that need it the most. By doing so, Bristol Meyer Squibb will get more back than just money for the bottom-line. They will get back their loyal consumers. This not about money, this about doing what is right and ethical.

I urge Bristol-Meyer Squibb to do what is right and not just give us lip service.

Please take the time to sign the E-Petition this Holiday Season. We won’t stop until the injustice has been righted. As a consumer of BMS products we can make a difference




Take Care,

Jimmy B

A Review of Treatments for Patients with Metastatic Melanoma | OncoLink Cancer Resources

A Review of Treatments for Patients with Metastatic Melanoma | OncoLink Cancer Resources

Take Care,

Jimmy B

Bristol Myers Squibb to pay 515 million to Settle Fraud Charges 2007 Melanoma..Jim Breitfeller

Shortage of Ipilimumab, I don't think so. I think it was staged to save and revert the drug to other Clinial trials. That is my opionion. Go to Clinical Trials. In the search field, type, Ipilimumab, Melanoma, protrate cancer, breast cancer,colon cancer, liver cancer. Then see when the trials that are recruiting and start date.

If it is after 8-12-2008, then the clinical trials was started with Ipilimumab after they took away compassionate drug use for the Melanoma Patients and is unethical to say the least.



Drugs giant Bristol-Meyers Squibb and a former subsidiary have been hauled over the coals and forced to pay more than half a billion dollars to settle settle federal and state investigations for promoting an anti-psychotic drug, Ablify, for uses that were not approved by the US Food and Drug Administration and providing illegal inducements to doctors and other health care providers.

The inducements included consulting fees and all expenses paid trips to resorts to attend conferences. There were also allegations that Bristol-Myers Squibb was behind the submission of false or fraudulent claims to medicaid, Medicare and other federal health programs.

Bristol Myers Squibb_pinged_515_million_to_settle_fraud_charges





Take Care,

Jimmy B

"Extraordinary Measures" Melanoma..Jim Breitfeller

"Extraordinary Measures"
Isn't this what we are trying to do?

Save our lives, save our love ones,

We have a theory, we need a clinical Trial to prove the theory.

Melanoma and the Magic Bullet (Monoclonal Antibodies)


Melanoma and the Magic Bullet (Monoclonal Antibodies)


We are Taking "Extraordinary Measures"

"Extraordinary Measures"




Take Care,

Jimmy B

I Support a Federal Ban on the sale of Indoor UV Tanning Exposure to Minors - Petition - Sign this petition here - Signature page - GoPetition

I Support a Federal Ban on the sale of Indoor UV Tanning Exposure to Minors - Petition - Sign this petition here - Signature page - GoPetition

Take Care,

Jimmy B

If you believe what Bristol-Meyer Squibb is telling us about the shortage watch This.Melanoma..Jim Breitfeller

Ex Drug Rep -- Manipulating Doctors

If they can manipulate Doctors, just think what they can do to the patients.

Watch the last two minutes.




Take Care,

Jimmy B

A Call for Patients for Dr. Rosenberg's Clinical Trials

"We continue to see a high rate of clinical responses in our cell transfer immunotherapy treatments for patients with metastatic melanoma", Dr. Rosenberg said.

"We are actively seeking patients for these trials and any note of that on a patient-directed web site would be appreciated."

If you would like to apply for his trials, here is the website and information.



Dr. Rosenberg's information




Dr. Rosenberg's Clinical Trials






Take Care,

Jimmy B

Don't Change to MPV Healthcare in Rochester, New York!!! Melanoma.. Jim Breitfeller

If you are thinking of changing Heathcare in Rochester, NY, don't. MPV Healthcare won’t process the request for CT scan of the CAP until they get the recent clinical reports and dates of the last chemo/immuno that was done. They are making us jump through hoops again. This Heathcare provider is nothing but trouble. Go with blue cross/shield if you can. You may be better off. Melanoma. I have reported them to CMS, my Congress persons,OFFICE OF THE NEW YORK STATE ATTORNEY GENERAL. Imagine,what about the old folks that don't have anyone to help them for fight for what is right. What is this world coming to???? Anything to save a buck and help the bottom line.

This really gets me fired up!!!!!!

This not the first time MPV Healthcare has denied us critical access to my Oncologist and my standard of care.

Lets keep track on how long it takes MPV Healthcare to approve the CT scan.

Take Care,

Jimmy B

Man stands up for an ideal, or acts to improve the lots of others..Melanoma..Jim Breitfeller

Robert Kennedy said, "Few will have the greatness to bend history; but each of us can work to change a small portion of events, and in the total of all those acts will be written the history of a generation...it is from numberless diverse acts of courage and belief that human history is thus shaped. Each time a man stands up for an ideal, or acts to improve the lots of others, or strikes out against injustice, he sends forth a tiny ripple of hope, and crossing each other from a million different centers of energy and daring, those ripples build a current which can sweep down the mightiest wall of oppression and resistance."

This is a excerpt from a close friend from the Melanoma Community.

"Some of you have inquired about contacting administrators and clinical researchers both at Roche=BRAF and Bristol Myers Squib= Iplilmumab in order to have Bob get access to the clinical trials currently being done on Metastatic Melanoma. You are RIGHT ON! Indeed we must gather together and on behalf of Bob and so many more people we must contact these drug makers. Jimmy Breitfeller is a Carepage friend of ours who has beaten back his own beast of Metastatic Melanoma and has become a national advocate for those of us who are struggling with this disease. He is known as “The Melanoma Missionary” because of his daily dedication to cure of Melanoma. He has a petition that we can all sign entitled BMS COMPASSSIONATE INVESTIGATIONAL DRUG ACCESS. The electronic petition is located on his Blog

http://melanomamissionary.blogspot.com/ When you go to Jimmy's Blog you will read all his research and advocacy. This petition has taken his advocacy to a new level and it has been very effective in getting attention from the key decision makers at drug companies treating melanoma patients. It is critical for people like us to speak out and sign a petition to our government, whether it be the FDA or Congress and the Senate about the laws of Compassionate Care. Our officials need to be educated, especially when Healthcare is being debated RIGHT NOW in the Senate, and make the understand exactly what BIG PHARMA is doing correctly or NOT doing to help people who need access to medicine that might bring a cure to their diseases.

Day in and day out I read Carepages and talk to people who are at the end of their life. What I have learned from them and many of you who take the time to be updated on Bob's Journey is that we are all part of a much larger chain of life than we realize. Speaking only for myself, I have found internal happiness and joy when I have joined in the larger story, focusing less on myself and small issues and joining something wider. As you sign petitions and advocate for our loved one I think you will get a sense of what I feel on a daily basis working "the systems" to try gain access in order to find a cure for Bob's cancer. It is a kind of focus on our core purpose as a collective, which is to hand off a better world to the next generation, I find a deep sense of purpose. This is basically to say that some of the greatest joys and happiness these last 7 3/4 months has come from feeling in some small way together with Jimmy Breitfeller and many many many others we have contributed to making things better - especially for melanoma patients. What really does matter is how we treat each other.

Robert Kennedy said, "Few will have the greatness to bend history; but each of us can work to change a small portion of events, and in the total of all those acts will be written the history of a generation...it is from numberless diverse acts of courage and belief that human history is thus shaped. Each time a man stands up for an ideal, or acts to improve the lots of others, or strikes out against injustice, he sends forth a tiny ripple of hope, and crossing each other from a million different centers of energy and daring, those ripples build a current which can sweep down the mightiest wall of oppression and resistance."

Shabbat Shalom

I am proud to be a nanoparticle in this movement. See as particles get heated up, they move faster and faster. We start to collide with other things, this inturn starts everything into motion. Energy released from this motion may be in the form of heat. Heat can be good or bad. It just depends on which side you are on.

Please Join the movement. We owe it to all Cancer Patients around the world.

Take Care,

Jimmy B

Keep those E Petitions Signatures for Bristol Meyer Squibb Coming.Melanoma.Jim breitfeller

It is not over until we get the IVs!!!!!!

We Need Bristol-Meyer Squibb to Open the Compassionate use of Ipilimumab to the Melanoma Patients who need it the most Stage IV Metastatic



Take Care,

Jimmy B

E Petition For BMS's Compassionate Investigational Drug Access.Melanoma..Jim Breitfeller

E Petition For BMS's Compassionate Investigational Drug Access

“You Can’t Start a Fire Without a Spark!!”

It is time to rally the Melanoma Patients and take back the Clinical Trials.

Bristol-Meyer Squibb halted the compassionate Drugs stating a drug shortage. There is evidence out there that the shorage was over months ago. They left the Melanoma Patients falling through the cracks of the Health Care System. We need change NOW!!!!!

Please sign the E Petition at Melanoma Missionary

Take Care,

Jimmy B

Sent a Letter to Dr. Margaret Hamburg, Commissioner of Food and Drugs.Melanoma..Jim Breitfeller

Sent a Letter to Dr. Margaret Hamburg, Commissioner of Food and Drugs.

Dr. Margaret Hamburg,



I am a melanoma patient/survivor/researcher, who has been stabilized by the use of Ipilimumab (Anti-CTLA-4 Blockage). BMS/Medarex stopped compassionate care use due to a shortage they say. It has been over a year (9/12/2008) since Melanoma patients that need the drug as a last resort of survival, have been left out of Clinical Trials which seems to me to be unethical. I know for a fact that it only takes 3 months to make and certify a batch of this monoclonal antibody. In fact, I contacted your shortage team a number of times. This drug never showed up on the shortage list and as a matter of fact, Bristol-Meyer Squibb has made a number of batches. They continued to start up new clinical trials, while leaving the most vulnerable to fall though the cracks of our Heath System.



I asked you to please show some compassion and look into this matter. I hope it doesn’t fall on deaf ears.




Take Care,

Jimmy B


-----Original Message-----
From: dbreitfe [mailto:dbreitfe@rochester.rr.com]
Sent: Friday, August 14, 2009 11:35 AM
To: 'CDER DRUG SHORTAGES'
Subject: RE: Anti-CTLA-4 blockage shortage.... Medarex and BMS



It has been almost a year that they said they have a production problem. I don’t think so.



Where is the compassionate use????????????????



Please investigate!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!



There is no Shortage!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! It is Greed!!!!!!!!!!!!!!!!!!!!!!! And Monopoly. It all comes down to money and the string of Pearls



Medarex 1999



http://findarticles.com/p/articles/mi_m0DED/is_7_19/ai_53992410/

Medarex (Annandale, NJ) recently announced that Centocor has paid $4 million in milestone fees for its use of the HuMab-Mouse technology. Separately, the company announced a new licensing agreement for the HuMab technology with Immunex Corp. Centocor holds exclusive commercial licenses to develop HuMab antibodies on four licensed targets.

“sing the HuMab-Mouse technology, Centocor researchers have obtained a number of product candidates, including an anti-IL-2 antibody of exceptionally high affinity. Immunex has obtained the right to use HuMab-Mouse for an unlimited number of targets for up to 10 years. Medarex will receive technology access fees, and cold receive research payments, license fees, milestone payments, and royalties on any commercial sales. HuMab-Mouse is a transgenic mouse system that creates high affinity, fully human antibodies. According Medarex, scientist can produce these antibodies in a matter of months. The agreement with Immunex is the tenth corporate partnership for Medarex involving its HuMab-Mouse system. Other partners include Bristol-Myers Squibb, Novartis Pharma AG, and Schering AG”





Where is the shortage if they can make product in a matter of months.



Sounds very fishy to me

===============================================================================

Posted by Jim Breitfeller at 08:38 on Fri, Oct 02, 2009 [Show other posts by Jim Breitfeller]

In Reply to: Re: A new clinical trial has been launched using patients' own immune systems by I know this is bothering you..... posted at 08:32 on Fri, Oct 02, 2009

Bristol-Meyer Squbibb is unethical in my opinion.

I go my dose of Ipilimumab. It saved my life.

I am fighting for all the others that are too sick to fight.

Posted by Tim--MRF at 02:47 on Mon, Sep 28, 2009 [Show other posts by Tim--MRF]

In Reply to: Bristol-Meyer Squibb has a lot to Explain!! Ipilimumab compassionate use by Jim Breitfeller posted at 08:03 on Mon, Sep 28, 2009

Jim:

I have had the opportunity to meet with several people at BMS who are involved in ipi and can tell you that they share your frustration. The official word is that when they applied for compassionate use approval they underestimated the demand they would face. That plus the fact that people were surviving longer on the drug placed an unanticipated strain on capacity, resulting in suspending the compassionate use program. They have a new batch of ipi available, but are holding off on compassionate use until they are absolutely sure they have enough to fulfill the requirements of the clinical trials. I have heard that the trials are largely enrolled and that many trials have waiting lists. I have sent a note to the people I met at BMS and asked them two questions you raise: Why did the new batch take so long? And, when do they expect compassionate use to be re-opened? The word I had earlier was the first quarter of 2010. I will post again when and if I get a reply.

I have tried to encourage them to provide regular updates on status--people definitely want to know what is going on.

Tim

Best to all

On June 11, 2007, BMS agreed to plead guilty and pay a $1 million criminal fine for misleading the government about the Plavix patent deal. BMS paid the maximum fine permitted by statute for committing two violations under the federal False Statements Act."



They mislead Government officials so why would they tell us the Patients, the truth about the shortage?



April 25 2008



Medarex and Bristol-Myers Squibb Joint Statement on Submission Status of Ipilimumab



PRINCETON, N.J., April 25 2008 /PRNewswire-FirstCall/ -- Medarex, Inc.

(Nasdaq: MEDX) and Bristol-Myers Squibb Company (NYSE: BMY) today announced that, after meeting with the U.S. Food and Drug Administration (FDA), the companies will delay the Biologics License Application (BLA) submission for ipilimumab, an investigational immunotherapy for patients with advanced metastatic melanoma. The FDA has requested additional overall survival (OS)data to further demonstrate the benefit of ipilimumab. Revised timelines are under development, but a BLA for ipilimumab will not be submitted to the FDA in 2008.



As far as my research to date(10-22-2009), BMS/Medarex has not file a BLA with the FDA.





On September 12 2008 they closed the compassionate use for Ipilimumab



Your email was forwarded to us by CBER (this IND resides in the Center for Drugs Evaluation and Research). We have contacted BMS to check into the availability of ipilimumab and here is the information that BMS provided to us.



“Toensure treatment is not interrupted for patients currently receiving ipilimumab and to provide ongoing supply to the registrational program, Bristol-Myers Squibb and Medarex have suspended enrollment of new patients into the compassionate use program, single patient exemptions and initiation of some non-registrational trials effective September 12, 2008.



Bristol-Myers Squibb and Medarex are working to manage the supply issue and may be able to re-open compassionate use in the future.



The companies are committed to providing uninterrupted treatment to patients who initiate therapy with ipilimumab. Therefore, if and when the compassionate use program reopens, it will be at such time when continuous and unconstrained supply is available."



Please let us know if you have any questions.



Sincerely,

CDER Drug Shortage Team





It Takes about a month to make a batch of monoclonal antibodies. By the time the batch is tested and packaged and approved, let us allow another two months. So in a year you should be able to make 3 to 4 batches.





Melanoma Treatment Information - Updated 09.10.09



Ipilimumab which ASCO reported some promising results had been widely available in compassionate use trials across the county until a shortage halted the studies. Bristol Myers Squibb, is now manufacturing the drug again and there are a few small “pharmacokinetic” trials to prove the agent is the same as the previous one used in trials. Most of these trials already have waiting lists, but it may be worth checking out. Screening started August 4th and you can find the locations on www.clinicaltrials.gov.

Source:https://www.z2systems.com/np/clients/mif/news.jsp?news=381



https://www.z2systems.com/np/clients/mif/news.jsp?news=381



Well come to find out that BMS/Medarex is opening up new clinical trials with Ipilimumab and continue to keep the compassionate use trial closed. How ethical is that?



When big pharma is involved in clinical development, it usually means large-scale clinical trials with patients and multiple sites.



Here are the trials:



Study of Ipilimumab and Dasatinib Combination Therapy in Patients With Chronic or Accelerated Chronic Myeloid Leukemia

Start Date: August 2009

Estimated Study Completion Date: Feb 2011

Estimated Enrollment: 30

ClinicalTrials.gov Identifier: NCT00732186

Ipilimumab +/- Vaccine Therapy in Treating Patients With Locally Advanced, Unresectable or Metastatic Pancreatic Cancer

Start Date: February 2009

Estimated Study Completion Date: Feb 2013

Estimated Enrollment: 30

ClinicalTrials.gov Identifier: NCT00836407

Bevacizumab Plus Ipilimumab in Patients With Unresectable Stage III or IV Melanoma

Start Date: February 2009

Estimated Study Completion Date: Feb 2011

Estimated Enrollment: 33

ClinicalTrials.gov Identifier: NCT00790010

Laboratory-Treated T Cells With or Without Ipilimumab in Treating Patients With Metastatic Melanoma

Start Date: February 2009

Estimated Study Completion Date: Feb 2011

Estimated Enrollment: 30

ClinicalTrials.gov Identifier: NCT00871481

Study of Immunotherapy to Treat Advanced Prostate Cancer

Start Date: May 2009

Estimated Study Completion Date: December 2012

Estimated Enrollment: 800

ClinicalTrials.gov Identifier: NCT00861614

Further study details as provided by Bristol-Myers Squibb:





These are all trials that were started after the halting of the compassionate Use. Bristol-Meyer Squibb thinks we the Melanoma Patients are expendable so they continued there quest to seek out new uses for the Drug.



Get a bigger bang for the buck.



They already know it will work well with Melanoma so why not find other uses.



Base on my calculation, 923 late stage Melanoma Patients were denied the drug while Bristol–Meyer Squibb continued to apply and start up new trials.







Bristol-Meyer Squibb Quote:



“What sets us apart? We believe it's our commitment to patients with serious diseases, our focus on finding innovative medicines that combat those diseases, and our dedication to extending and enhancing human life.”



All Lip Service!!!!!!



“Jim, thank you so much for your efforts. My father passed away this past March. He was also scheduled to start the ipi trial last year and found out the Saturday before he was to go in that the compassionate use trial was suspended. He developed 3 mets in his brain by Thanksgiving. The ipi trials with brain mets were closed to new patients by then. I've spent countless hours and days frustrated and angry, unable to express or figure out what you have with BMS and wanting to take some sort of action. I also sent letters, made phone calls, etc. One day, someone will be able to stop these drug companies from playing with our lives. Please keep me posted in your findings.”







Update on Ipilimumab



Ipilimumab is not back yet. Patients are not being encouraged to wait for Ipilimumab to become available for now. The only Ipilimumab melanoma trials currently enrolling new patients in the US are the brain metastases trial (CA-184042) and the phase 3 adjuvant trial (CA-184029) because the supply for those trials was protected in advance. Bristol Myers Squibb is working diligently to overcome the drug shortage, but can’t guarantee a time that it will return to the compassionate use setting

Source: Melanoma International Foundation: https://www.z2systems.com/np/clients/mif/news.jsp?news=376





Response from BMS as of 10-21-2009



“Regarding compassionate use, as you are aware, the rate of enrollment in the compassionate use program for ipilimumab was greater than anticipated with 30 to 40 percent of patients continuing on therapy beyond the initial induction schedule. This demand depleted drug supply at a faster rate than anticipated. Bristol-Myers Squibb had to suspend enrollment of new patients into the compassionate use program and single patient exemptions to ensure treatment is not interrupted for patients currently receiving ipilimumab and to provide supply for ongoing clinical studies.



We are working through the manufacturing and testing process, and continue to carefully manage the supply to enable the potential re-opening of compassionate use at the earliest possible time and when continuous supply is available.



Bristol-Myers Squibb remains committed to the development of ipilimumab and to addressing the great unmet medical need for patients with metastatic melanoma.”



As you can read, BMS is not even acknowledging that they even produced other batches.



We the Patients deserve better, We are the ones who are taking all the risk. We should have some control in this process.



We the Patients have had to hear it from second hand sources like the Melanoma International Foundation and Melanoma Research Foundation. I don’t believe that their ad advertisers (The Ogilvy Group Inc) can repair the public’s trust in this company.



This Month will be the anniversary of the discovery of Anti-CTLA-4 antibodies, celebrating ten years in the making of the drug. This is way to long for a drug to come to market. It usually takes 8.7 years for monoclonal antibodies. So what gives?




How Drugs are Developed and Approved by the FDA



http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/default.htm#

Immune System, White Blood Cells, T-Cells, Cancer Cells..Melanoma Jim Breitfeller

How cells activate and produce immune response .

Lifesaver... PLX-4032 Therapy for BRAF Mutations..Melanoma ..Jim Breitfeller

"Now, an incredible breakthrough. A tiny capsule that can stop even advanced Melanoma in its tracks.

It's called PLX 4032 — and the results are so swift and dramatic that it's got even the usually conservative medical community excited. Even better, this drug could mark the beginning of a cure for other forms of cancer. Already, it's giving some patients back their lives and, for people like 24-year-old Brendan Robbins, offering hope — just in time."

Reporter: Liz Hayes
Producer: Phil Goyen

Lifesaver... PLX-4032 Therapy for BRAF Mutations



Source:http://sixtyminutes.ninemsn.com.au/stories/927744/lifesaver-cancer

You may want to be checked for the BRAF Mutation.

Take Care,

Jimmy B

Study Reveals a "Missing Link" in Immune Response to Disease – 2009 Press Releases - Dana-Farber Cancer Institute

Study Reveals a "Missing Link" in Immune Response to Disease – 2009 Press Releases - Dana-Farber Cancer Institute

Take Care,

Jimmy B

Video: Activating T Cells Response to Disease - Dana-Farber Cancer Institute

Video: Activating T Cells Response to Disease - Dana-Farber Cancer Institute

Take Care,

Jimmy B

Tumors as elusive targets of T-cell-based Active Immunotherapy..Melanoma..Jim Breitfeller

Dr. Herlyn, I been researching my successful Melanoma treatment and came across a research paper of yours “Tumors as elusive targets of T-cell-based active immunotherapy”. It postulates the mechanism underlying is the Antigen-Specific T-cell base immunotherapy can result in a complete response if activated appropriately. I believe that you diagram was right on target. My therapy was three clinical trials that followed your proposed mechanism. I did DTIC + PaTrin-2 to shed the right antigenic protein. Then I used Anti-CTLA-4 blockage to activate CD4+ T-cells and suppress the Tregs. IL-2 HD was added to help differentiate the T-cells and maintain there function and survival. Timing and dosing concentration played a major factor in breaking the balance of the tumor’s microenvironment. During my therapy I did get an inflammation response leading to a complete response.



Attached is a draft of what transpired and the dosing and timing. I believe this information might be very helpful in your research.
(See My Shared files)



"Melanoma and the Magic Bullet (monoclonal antibodies"



Fig. 2. Postulated mechanism underlying tumor antigen (TA)-specific T-cell-based immunotherapy and effect on target antigen expression. Localization of TA-specific
T cells at a tumor site appears to be necessary but not sufficient for tumor elimination [38,39]. If no response occurs, the interaction between T cell and tumor cell is
probably not sufficient (or sustained) to start or maintain an inflammatory process. If the treatment induces an adaptive response of a quality and/or intensity that exceeds
a certain ‘threshold’, then direct interaction of T cells with antigen-expressing (red circles) tumor cells leads to their destruction, as well as to the production of proinflammatory
and pro-apoptotic cytokines that induce secondary activation of adaptive and innate immune effectors capable of clearing tumor cells that have lost antigen
expression (white circles). If the tumor-cell destruction is not complete, the proliferation of remaining cells leads to recurrence. In those cases, the recurring tumors have
lost the surface expression of the epitope relevant to the vaccination [66,67]. Abbreviations: CR, complete response; PR, partial response; X, cells killed by the therapy.

Source:http://www.wistar.org/Herlyn/Pub%20PDFs/Marincola2003pdf.pdf

Tumors as elusive targets of
T-cell-based active immunotherapy

As you can see, the maxium Antibody level occurs on day 20. My Inflamed response occurred on day 15. This all fits together.






Take Care,

Jimmy B

Bristol-Meyer Squibb, Show Us the Patients, the Master Production Batch Record (MPBR) or Production Batch Record (PBR) for Ipilimumab

Bristol-Meyer Squibb, If there was truly a Shortage/problem in the production of Ipilimumab, the it would show up in the Master Production Batch Record (MPBR) or Production Batch Record (PBR)

“A master production batch records (MPBR) is a detailed, step-by-step description of the entire production process for a specific drug. It is the document wherein the chemical and biological processes of drug manufacturing (developed during the phase of research and process development of the drug) are merged with the regulatory requirements of the FDA. A good batch record ensures the fundamentals of cGMP compliance while providing a practical set of instructions for the manufacturing technician or operator. The MPBR explains exactly how the product is produced, indicating specific types and quantities of components and raw materials, processing parameters, in-process quality controls, environmental controls, etc. To support the requirements of the production batch record (PBR) which is also known as the batch production and control record, the MPBR contains fill-in-the-blank spaces throughout the text to facilitate the documentation of events for each individual batch. In fact the PBR is an exact copy of an approved MPBR. A PBR is issued for each batch of product produced in the facility. A batch, by the way, is defined in the Code of Federal Regulations, Title 21 210.3: "Batch means a specific quantity of a drug or other material that is intended to have a uniform character and quality, within specified limits, and is produced according to a single manufacturing order during the same cycle of manufacturing." For a cell-culture derived protein product, a batch begins with inoculation and then proceeds through harvest and purification (sometimes the final purification steps may have a separate batch record). There would be separate batch records for media preparation, equipment preparation (cleaning, assembly, sterilization, etc.), and scale-up for innoculum preparation. There would also be separate batch records for final product formulation, filtration, filling, lyophilization, sealing, inspection, and labeling. PBRs must be followed during production events, and the information and signature blocks must be completed as production proceeds. Production and QC personnel write the MPBR.”

This Document would be the proof that there was or wasn’t a shortage/problem.

We would also like a copy of the production log book ledger dating back to 7-1-2008.



Facts About Current Good Manufacturing Practices (cGMPs)http://www.fda.gov/Drugs/DevelopmentApprovalProcess/Manufacturing/ucm169105.htm#

fda.gov/Drugs/DevelopmentApprovalProcess/Manufacturing


Take Care,

Jimmy B

Why Should We Believe That There Was Even a Shortage of Ipilimumab?Melanoma ..Jim Breitfeller

On June 11, 2007, BMS agreed to plead guilty and pay a $1 million criminal fine for misleading the government about the Plavix patent deal. BMS paid the maximum fine permitted by statute for committing two violations under the federal False Statements Act."

They mislead Government officials so why would they tell us the Patients, the truth about the shortage?

April 25 2008

Medarex and Bristol-Myers Squibb Joint Statement on Submission Status of Ipilimumab

PRINCETON, N.J., April 25 2008 /PRNewswire-FirstCall/ -- Medarex, Inc.
(Nasdaq: MEDX) and Bristol-Myers Squibb Company (NYSE: BMY) today announced that, after meeting with the U.S. Food and Drug Administration (FDA), the companies will delay the Biologics License Application (BLA) submission for ipilimumab, an investigational immunotherapy for patients with advanced metastatic melanoma. The FDA has requested additional overall survival (OS)data to further demonstrate the benefit of ipilimumab. Revised timelines are under development, but a BLA for ipilimumab will not be submitted to the FDA in 2008.

As far as my research to date(10-22-2009), BMS/Medarex has not file a BLA with the FDA.


On September 12 2008 they closed the compassionate use for Ipilimumab

Your email was forwarded to us by CBER (this IND resides in the Center for Drugs Evaluation and Research). We have contacted BMS to check into the availability of ipilimumab and here is the information that BMS provided to us.

"To ensure treatment is not interrupted for patients currently receiving ipilimumab and to provide ongoing supply to the registrational program, Bristol-Myers Squibb and Medarex have suspended enrollment of new patients into the compassionate use program, single patient exemptions and initiation of some non-registrational trials effective September 12, 2008.

Bristol-Myers Squibb and Medarex are working to manage the supply issue and may be able to re-open compassionate use in the future.

The companies are committed to providing uninterrupted treatment to patients who initiate therapy with ipilimumab. Therefore, if and when the compassionate use program reopens, it will be at such time when continuous and unconstrained supply is available."

Please let us know if you have any questions.

Sincerely,
CDER Drug Shortage Team


It Takes about a month to make a batch of monoclonal antibodies. By the time the batch is tested and packaged and approved, let us allow another two months. So in a year you should be able to make 3 to 4 batches.


Melanoma Treatment Information - Updated 09.10.09

"Ipilimumab which ASCO reported some promising results had been widely available in compassionate use trials across the county until a shortage halted the studies. Bristol Myers Squibb, is now manufacturing the drug again and there are a few small “pharmacokinetic” trials to prove the agent is the same as the previous one used in trials. Most of these trials already have waiting lists, but it may be worth checking out. Screening started August 4th and you can find the locations on www.clinicaltrials.gov."

Source:https://www.z2systems.com/np/clients/mif/news.jsp?news=381

Melanoma International Foundation


Well come to find out that BMS/Medarex is opening up new clinical trials with Ipilimumab and continue to keep the compassionate use trial closed. How ethical is that?

When big pharma is involved in clinical development, it usually means large-scale clinical trials with patients and multiple sites.

Here are the trials:

Study of Ipilimumab and Dasatinib Combination Therapy in Patients With Chronic or Accelerated Chronic Myeloid Leukemia
Start Date: August 2009
Estimated Study Completion Date: Feb 2011
Estimated Enrollment: 30
ClinicalTrials.gov Identifier: NCT00732186

Ipilimumab +/- Vaccine Therapy in Treating Patients With Locally Advanced, Unresectable or Metastatic Pancreatic Cancer
Start Date: February 2009
Estimated Study Completion Date: Feb 2013
Estimated Enrollment: 30
ClinicalTrials.gov Identifier: NCT00836407

Bevacizumab Plus Ipilimumab in Patients With Unresectable Stage III or IV Melanoma
Start Date: February 2009
Estimated Study Completion Date: Feb 2011
Estimated Enrollment: 33
ClinicalTrials.gov Identifier: NCT00790010

Laboratory-Treated T Cells With or Without Ipilimumab in Treating Patients With Metastatic Melanoma
Start Date: February 2009
Estimated Study Completion Date: Feb 2011
Estimated Enrollment: 30
ClinicalTrials.gov Identifier: NCT00871481

Study of Immunotherapy to Treat Advanced Prostate Cancer
Start Date: May 2009
Estimated Study Completion Date: December 2012
Estimated Enrollment: 800
ClinicalTrials.gov Identifier: NCT00861614

Further study details as provided by Bristol-Myers Squibb:


These are all trials that were started after the halting of the compassionate Use. Bristol-Meyer Squibb thinks we the Melanoma Patients are expendable so they continued there quest to seek out new uses for the Drug.

Get a bigger bang for the buck.

They already know it works well with Melanoma, so why not find other uses.

Base on my calculation, 923 late stage Melanoma Patients were denied the drug while Bristol–Meyer Squibb continued to apply and start up new trials.



Bristol-Meyer Squibb Quote:

“What sets us apart? We believe it's our commitment to patients with serious diseases, our focus on finding innovative medicines that combat those diseases, and our dedication to extending and enhancing human life.”

All Lip Service!!!!!!

“Jim, thank you so much for your efforts. My father passed away this past March. He was also scheduled to start the ipi trial last year and found out the Saturday before he was to go in that the compassionate use trial was suspended. He developed 3 mets in his brain by Thanksgiving. The ipi trials with brain mets were closed to new patients by then. I've spent countless hours and days frustrated and angry, unable to express or figure out what you have with BMS and wanting to take some sort of action. I also sent letters, made phone calls, etc. One day, someone will be able to stop these drug companies from playing with our lives. Please keep me posted in your findings.”



Update on Ipilimumab

Ipilimumab is not back yet. Patients are not being encouraged to wait for Ipilimumab to become available for now. The only Ipilimumab melanoma trials currently enrolling new patients in the US are the brain metastases trial (CA-184042) and the phase 3 adjuvant trial (CA-184029) because the supply for those trials was protected in advance. Bristol Myers Squibb is working diligently to overcome the drug shortage, but can’t guarantee a time that it will return to the compassionate use setting.

Source: Melanoma International Foundation:
https://www.zsystems.com/np/clients/mif/news.jsp?news=376


Melanoma International Foundation



Response from BMS as of 10-21-2009

“Regarding compassionate use, as you are aware, the rate of enrollment in the compassionate use program for ipilimumab was greater than anticipated with 30 to 40 percent of patients continuing on therapy beyond the initial induction schedule. This demand depleted drug supply at a faster rate than anticipated. Bristol-Myers Squibb had to suspend enrollment of new patients into the compassionate use program and single patient exemptions to ensure treatment is not interrupted for patients currently receiving ipilimumab and to provide supply for ongoing clinical studies.

We are working through the manufacturing and testing process, and continue to carefully manage the supply to enable the potential re-opening of compassionate use at the earliest possible time and when continuous supply is available.

Bristol-Myers Squibb remains committed to the development of ipilimumab and to addressing the great unmet medical need for patients with metastatic melanoma.”

As you can read, BMS is not even acknowledging that they even produced other batches.They are hiding the fact that they are back online. Their communication skills with the public/patients are NIL. Instead they are starting new protocols with Ipilimumab. Where is the FDA in al of this? Who is watching the hen house?

When I searched for drug shortages on the FDA website, Ipilimumab did not show up.

What is going on?

We the Patients deserve better, We are the ones who are taking all the risk. We should have some control in this process.

We the Patients have had to hear it from second-hand sources like the Melanoma International Foundation and Melanoma Research Foundation. I don’t believe that their ad advertisers (The Ogilvy Group Inc) can repair the public’s trust in this company. They have major issues.

This Month will be the anniversary of the discovery of Anti-CTLA-4 antibodies, celebrating ten years in the making of the drug. This is way to long for a drug to come to market. It usually takes 8.7 years for monoclonal antibodies. So what gives?

I hope see some dialog started between the patients and BMS. BMS needs somehow to regain the public's trust.

I am under the impression that greed and power-play is mixed in all of this. It all has to do with the STRING OF PEARLS intiative.



How Drugs are Developed and Approved by the FDA?

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/default.htm#


How Drugs are Developed and Approved by the FDA



Take Care,

Jimmy B

Hope!! Yes we Can!! Melanoma..Jim Breitfeller

Message of HOPE from Karen Velasquez 10/2009

Turn off Music before playing







Take Care,

Jimmy B

Main roads to melanoma..Jim Breitfeller

Main roads to melanoma

This paper is very technical but gives great insight into Melanoma and the pathways that are associated with it. It is quite long and should be read in small bites. Please don't be intimidated by it.

Giuseppe Palmieri1, MariaElena Capone2, MariaLibera Ascierto2, Giusy Gentilcore2, David F. Stroncek3, Milena Casula1, MariaCristina Sini1, Marco Palla2, Nicola Mozzillo2, and Paolo A. Ascierto*2


ABSTRACT

The characterization of the molecular mechanisms involved in development and progression of melanoma could be helpful to identify the molecular profiles underying aggressiveness, clinical behavior, and response to therapy as well as to better classify the subsets of melanoma patients with different prognosis and/or clinical outcome. Actually, some aspects
regarding the main molecular changes responsible for the onset as well asthe progression of melanoma toward a more aggressive phenotype have been described. Genes and molecules which control either cell proliferation, apoptosis, or cell senescence have been implicated. Here we provided an overview of the main molecular changes underlying thepathogenesis of melanoma. All evidence clearly indicates the existence of a complex molecular machinery that provides checks and balances in normal melanocytes. Progression from normal melanocytes to malignant metastatic cells in melanoma patients is the result of a combination of downor up-regulation of various effectors acting on different molecular pathways.

Source:
http://www.translational-medicine.com/content/pdf/1479-5876-7-86.pdf

Main Roads to Melanoma



Take Care,

Jimmy B

The Top 5 Most Promising Upcoming Drugs for Melanoma..Jim Breitfeller

New Phase III Clinical Trials for the Treatment of Melanoma
From Timothy DiChiara, Ph.D., for About.com
Created: May 21, 2009

About.com Health's Disease and Condition content is reviewed by the Medical Review Board


Treatment of advanced (stage III and IV) melanoma is in desperate need of some good news. Although the incidence of melanoma is increasing by a whopping 3 to 5% per year in the United States, current therapies don't significantly increase survival in most patients and no new first-line medicines have been approved in over 10 years.
Clinical trials are the best hope for a long-lasting reduction or elimination of metastatic melanoma (called a "durable response" or "complete response" by doctors). The US National Institutes of Health lists 27 late-stage (phase III) clinical trials currently recruiting patients with melanoma. Many of the trials are testing new combinations of existing drugs, new ways to administer them, or new surgical procedures, but some are investigating brand new drugs. The most promising are the following:

Allovectin-7 - This novel gene therapy is injected directly into the tumors of patients with stage III or IV disease, which then alerts the body's own immune system to attack the tumor. Earlier trials of Allovectin alone showed that tumors in 4% to 9% of patients responded to the therapy. The new trial is comparing Allovectin-7 to the standard chemotherapy treatment, either dacarbazine or temzolomide. Made by Vical. Find out if you may qualify for the AIMM trial of Allovectin-7.

oblimersen (Genasense) - Genasense is a unique inhibitor of Bcl-2, a protein made by cancer cells that is thought to block chemotherapy-induced cell death (called "apoptosis"). So by reducing the amount of Bcl-2 in cancer cells, Genasense may enhance the effectiveness of current anticancer treatment. Previous studies demonstrated that Genasense combined with the chemotherapy drug dacarbazine tripled response rate and significantly increased overall survival compared to dacarbazine alone. Made by Genta. Find out more about the AGENDA trial of oblimersen.

MVax - MVax is a melanoma vaccine prepared from the patient's own cancer cells. Several studies have shown that MVax followed by interleukin-2 can lead to a complete response in up to 13% of patients, double that of interleukin-2 alone. MVax is also effective in patients with stage III melanoma when given post-surgery: it doubled the 5-year survival rate compared to surgery alone. Made by AVAX Technologies. Find out more about the MVALDI trial for MVax.

ipilimumab (MDX-010, MDX-101, or BMS-734016) - Ipilimumab is an antibody that activates the body's immune system to fight melanoma by inhibiting the CTLA-4 molecule. Three previous phase II clinical trials have shown that treatment with ipilimumab results in a one-year survival rate of 47% to 51% for people with stage III or IV melanoma, which is almost double the average. The current trial is comparing ipilimumab to a dummy treatment (placebo) in patients with stage III melanoma who have already undergone surgery. Made by Medarex and Bristol-Myers Squibb. Find out more about the EORTC 18071 trial for ipilimumab.

OncoVEXGM-CSF - OncoVEXGM-CSF is a vaccine that works by spreading within tumors and causing the death of cancer cells while stimulating the immune system to destroy metastatic tumors. Previous results from 50 patients with inoperable stage IIIc/IV melanoma demonstrated that 28% of patients responded, including 12% with a complete response. The new trial is enrolling patients with previously treated but inoperable stage IIIb, IIIc or IV melanoma and is designed to compare OncoVEXGM-CSF to a naturally-occurring substance in the body called a "granulocyte monocyte colony stimulating factor" (GM-CSF), which increases white blood cells. Made by BioVex. Find out more about the trial for OncoVEXGM-CSF.

Why Participate in Clinical Trials

Those who take part in clinical trials get access to the latest treatments that are often not available anywhere else. These treatments may be better than the standard of care and may offer the only hope for those with advanced disease. Simply put, participation in clinical trials by patients like you is the only way research will advance toward an eventual cure for melanoma.

Talk about the possibilities with your doctor!

Source:

ClinicalTrials.gov. US National Institutes of Health. 10 February 2009.

Take Care,

Jimmy B

Take Care,

Jimmy B

This is why I am so upset.Melanoma..Jim Breitfeller

COPosted by Tim--MRF at 02:47 on Mon, Sep 28, 2009 [Show other posts by Tim--MRF](Melanoma Research Foundation)

In Reply to: Bristol-Meyer Squibb has a lot to Explain!! Ipilimumab compassionate use by Jim Breitfeller posted at 08:03 on Mon, Sep 28, 2009

Jim:

I have had the opportunity to meet with several people at BMS who are involved in ipi and can tell you that they share your frustration. The official word is that when they applied for compassionate use approval they underestimated the demand they would face. That plus the fact that people were surviving longer on the drug placed an unanticipated strain on capacity, resulting in suspending the compassionate use program. They have a new batch of ipi available, but are holding off on compassionate use until they are absolutely sure they have enough to fulfill the requirements of the clinical trials. I have heard that the trials are largely enrolled and that many trials have waiting lists. I have sent a note to the people I met at BMS and asked them two questions you raise: Why did the new batch take so long? And, when do they expect compassionate use to be re-opened? The word I had earlier was the first quarter of 2010. I will post again when and if I get a reply.

I have tried to encourage them to provide regular updates on status--people definitely want to know what is going on.

Tim

So why is the compassionate Use not first inline to get it?


It comes down to greed.They are looking after their bottom line but they preach:

What sets us apart? We believe it's our commitment to patients with serious diseases, our focus on finding innovative medicines that combat those diseases, and our dedication to extending and enhancing human life.”

All Lip Service!!!!!

THEY DID NOT EVEN HAVE THE DECENCY TO LET THE PATIENTS KNOW

Bristol-Meyer Squibb, LET YOUR TRUE COLORS COME SHINING THROUGH!!!!!!!

WHAT A BOONDOGGLE

THIS SHOULD BE REOPORTED TO THE FDA..CDER Drug Shortage Team

Take Care,

Jimmy B