Combinatorial Therapy, Will the Big Pharmaceutical Companies do what Is Ethically Right?Melanoma..Jim Breitfeller

Combinatorial Therapy, Will the Big Pharmaceutical Companies do what Is Ethically Right?




They include Plexikkon,Bristol-Myer Squibb, Pfizer, La Roche and Novartis.


I and other researchers have come to the conclusion that Combinatorial Therapy may be the only way to beat The BEAST, Melanoma



“A very obvious combination that we are trying to move forward now is PLX4032 with ipilimumab. There is unanimity among the academic researchers that this must be investigated. Both companies see the logic, but are reluctant with neither of their drugs yet being FDA approved. As you know ipilimumab (and tremelimumab) have not overwhelmed the FDA yet as they were told to show a response rate greater than 10% and neither drug could do so. Most melanoma researchers believe that there are additional patients who get real and long-term benefit without having their tumors shrink significantly in size, but the randomized trials are needed to show that. The worrying sign is the outcome of the tremelimumab randomized trial. So, now we are down to waiting for the results of the dacarbazine vs. dacarbazine plus ipilimumab phase III trial. If this is negative, we are in trouble as ipilimumab will have no clear path forward with the FDA. If it’s positive, then the idea of moving ahead with combinations becomes much, much easier. But, even it that trial is negative, we know that CTLA-4 blockade can induce phenomenal responses in some. So, in that case, we have to figure out (1) who those patients are and, (2) how to make those responses happen in more patients. The other way of thinking of #2 is that PLX4032 doesn’t work for as long as we would like and that making those responses more durable would be desirable.”


~ Dr. Keith Flaherty ~


“ 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.”


~ Dr. Craig Slingluff ~



Dr Markovic,. I thought you might be interested in this combinatorial therapy

“We actually just submitted a paper to this affect in a small clinical trial where we used a conventional chemotherapeutic agent to induce a systemic anti-tumor immune response by simply timing drug delivery. And, it worked! It was a small study, so the data is only descriptive. I'm gearing up to move to a large trial right now.”


~Dr. Svetomir Markovic~



“To answer your last question first: Mutations in B-Raf and N-Ras have been shown to cluster at specific nucleotides. This strongly suggests that there is a cellular mechanism which targets these sites in each gene. However, you are probably right, that anti-CTLA4 and IL2 are working by enhancing immune surveillance of your melanoma.”


~Dr. Natalie Ahn~



“In conclusion, the combination of MART-1/DC with concomitant tremelimumab is feasible in patients with metastatic melanoma, especially when tremelimumab is administered every 3 months, and results in durable objective clinical responses at the higher range of the expected objective tumor response rates with either therapy alone. Therefore, this combination warrants further study in patients with advanced malignant melanoma.”

~Dr. Antoni Ribas~


The rationale for the CTLA-4 and IL-2 combination is once you activated the CD4+ Tcell and it crossprime the CD8+ Tcell , the IL-2 needed for the maintenance and functionality of the CD8+ T-cell.
If lymphocytes are cultured in the presence of Interleukin 2, it results in the development of effector cells which are cytotoxic to tumor cells.

“Fine theory but just theory that has never been tested in relevant clinical setting…”

~Dr. John M. Kirkwood~

"Glad to see your post on this series. From our perspective, the melanoma community isn’t waiting for a “miracle” to fall out of the sky to help patients. It’s clear that no single drug will likely effectively treat the disease; instead, a combination of drugs may be the answer. The Melanoma Research Foundation (MRF) is coordinating the Melanoma Breakthrough Consortium to accelerate research by bringing together leaders in drug development, laboratory and clinical research to find effective treatments. This collaboration will take years off the process. Patients with advanced melanoma have few or no treatment options and there’s no doubt in the urgency of moving forward to test new therapies today. More information is available at http://www.melanoma.org."

~Tim Turnham~
Executive Director
Melanoma Research Foundation




This is why we the patients need the Pharmaceutical companies to work together. Each therapy will not work alone as a single agent. The response rate is between 10 and 22 percent for each therapy. If you do a sequential treatment with the proper dosage and timing, you will see a synergistic outcome.

“There are three parts of the equation in a clinical trial. There’s who has control, who gets the reward, and who takes the risk. Patients take all the risk, they have no control, and they get no reward. Patients ought to be the ones driving the process and get the reward out of it and have the control, since they are the ones that take the risk.”


~Greg Simons~


If we are taking all the risk, shouldn’t we have a say in our Destiny?
“We need to all work together for the common good of the Melanoma Patients”
“We need to take greed out of the equation and just do what is ethically for humanity”

~Jimmy B~

Which elevator will you, The Pharmaceuticals Companies will Take?



Take Care,

Jimmy B

What If you combine Therapies? Response from Dr. Keith Flaherty..Melanoma ..Jim Breitfeller

What If you combine Therapies? Response from Dr. Keith Flaherty

Jim,


Thanks for the note.




"It is actually critical “patient advocates” which obviously includes patients, as well as those who are motivated to advocate on behalf of patients get involved in this process. One of the very reasons why I thought that a consortium was important to form, so that there could at least a body of researchers to point to as a group jointly focused on this direction. You see, companies find it very easy to say no to individual investigators when it comes to “difficult” requests. We need to make it harder for them when it involves losing time that our patients don’t have."



A very obvious combination that we are trying to move forward now is PLX4032 with ipilimumab. There is unanimity among the academic researchers that this must be investigated. Both companies see the logic, but are reluctant with neither of their drugs yet being FDA approved. As you know ipilimumab (and tremelimumab) have not overwhelmed the FDA yet as they were told to show a response rate greater than 10% and neither drug could do so. Most melanoma researchers believe that there are additional patients who get real and long-term benefit without having their tumors shrink significantly in size, but the randomized trials are needed to show that. The worrying sign is the outcome of the tremelimumab randomized trial. So, now we are down to waiting for the results of the dacarbazine vs. dacarbazine plus ipilimumab phase III trial. If this is negative, we are in trouble as ipilimumab will have no clear path forward with the FDA. If it’s positive, then the idea of moving ahead with combinations becomes much, much easier. But, even it that trial is negative, we know that CTLA-4 blockade can induce phenomenal responses in some. So, in that case, we have to figure out (1) who those patients are and, (2) how to make those responses happen in more patients. The other way of thinking of #2 is that PLX4032 doesn’t work for as long as we would like and that making those responses more durable would be desirable.

The companies need to hear it from patients and all patient-advocates that fairly obvious directions need to be pursued to find multiplicative effects. For the first time in melanoma, we have the building blocks in front of us and scientific rationale to guide us for the next steps.


Best regards, Keith

+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
Keith,


Base on my research, Ipi doesn’t work well is because it is lacking the tumor-specific antigens. DTIC+ Patrin-2, Irradiation, Oblimersen and others. We need the tumors to shed antigenic protein. To get the immune response into motion.


By using PLX-4032, my guess it will shed the protein needed. Then Anti-CTLA-4 Blockage comes in. It leaves the cd4+ T-cell activated and at the same time suppresses the Treg function allowing the CD8+ T-cells to get crossed primed and have them break though the tumor microenvironment. The HD IL-2 is added at the peak expansion of the CD8+ T-cells ( 50 days after Ipi is introduced into the host.). IL-2 is essential in the survival and function of the CTLs.


The above is my take on this combinatorial therapy. If you want, I can send you all the supporting papers of this theory.


Also, Can I get your permission to post your reply on my Blog?

Best Regards

Jim

+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

What If you Combine three Therapies? PLX-4032 after remission, to let the tumor burden be low, Than add one dose of Anti-CTLA-4 Blockage. Wait 50 days so the CD8 T-cells would be at their maximum expansion. Then add two cycles of HD IL-2 to help grow and differentiate the CD8 T-cells into Cytotoxic T Lymphocytes (CTL's). You use the PLX-4032 to lower the tumor burden and shed the antigenic protein from the tumor.



For the patients that have the Braf mutation, use PLX-4032 to shed the antigenic protein and lower the tumor burden.

If you don't have the mutation, use radiation, chemo DTIC+ Patrin-2, Oblimersen and other small molecules to shed the antigenic protein.







Take Care,

Jimmy B

A note To Dr. Keith Flaherty.. Combinatorial Therapy..Melanoma..Jim Breitfeller..2-25-2010

"One year, Dr. Flaherty thought, when he heard the news. Certainly no triumph. But it was something. Something to be built on.

Novartis and Bristol-Myers had agreed to schedule teleconferences for later in the month to talk about combination trials. He checked the dates on his electronic calendar. A meeting with Pfizer was also pending."



Dr. Flaherty,

As early as May of 2009 I had come to the conclusion that the drug companies must work togther to come up with a stabilization/cure.

As a fellow researcher and Blogger, What can I do to help convince the pharma this it is in their best interest to work together. It would be a win, win for all, including the Patients like myself.

Keith, Please let me know what I can do to Help?

Best regards



Jim Breitfeller





Friday, May 8, 2009

There is Enough Room for Novartis, Bristol Meyer Squibb and Pfizer for each to take part in the Melanoma Space Melanoma.. Jim Breitfeller

There is Enough Room for Novartis, Bristol Meyer Squibb and Pfizer for each to take part in the Melanoma Space.

With ASCO Annual meeting coming up at the end of May, I believe that there will be some excitement around monoclonal antibodies. In particular, anti-CTLA-4 blockage treatment will be under the spotlight. What will the overall survival rates look like? Well, speaking from my experience, anti-CTLA-4 has prolonged my life for over 27 months where as a stage IV Patient, I was given 6 to 9 months. This could not have happen with out the extra help from Interleukin -2.

See, once the CD4+ T-cells activated, they need to grow and cross-prime the CD8+ T-cells. While activated T-cells secretes IL-2 at a certain concentration to help promote proliferation of the CD4+ T-cells. If there is too much IL-2 at the beginning of the immune response, I believe that the ratio of CD4/CD8/CD3 would be altered causing
the Tregs (CD4+ CD25 fox P3) to gain the upper hand of suppression of the immune response. A subset of CD4 + cells called CD4 + CD25 + regulatory T (Treg) cells that expresses Forkhead box P3 (Fox P3).

With just adding Anti-CTLA-4 first, It has been reported that it suppresses the T regs and pushes the balance towards an immune response. Once the immune response is in progress, the CD4+ T-cell is needed to co-stimulate the CD8+ T-cell. A source of these cofactors for effective CD8+ T-cell stimulation can be provided by CD4+ T cells that release critical amounts of IL-2.

Once the CD8+ T-cell is activated, and is cultured in the presence of Interleukin 2, it results in the development of effector cells which are cytotoxic to tumor cells.

This is why we the patients need the Pharmacitical companies to work together. Each therapy will not work alone as a single agent. The response rate are between 10 and 22 percent for each therapy. If you do a sequential treatment with the proper dosage and timing, you will see a synergistic outcome.


“There are three parts of the equation in a clinical trial. There’s who has control, who gets the reward, and who takes the risk. Patients take all the risk, they have no control, and they get no reward. Patients ought to be the ones driving the process and get the reward out of it and have the control, since they are the ones that take the risk.”

~Greg Simons~


If we are taking all the risk, shouldn’t we have a say in our Destiny?

“We need to all work together for the common good of the Melanoma Patients”

“We need to take greed out of the equation and just do what is right for humanity”




Melanoma and The Magic Bullet (Monoclonal Antibodies)




Take Care,

Jimmy B

Watch Dr Jeff Weber, Florida, USA, ANTI-CTLA-4: A new immunological approach on ecancer tv. Cancer journal: online cancer news, clinical oncology research

Watch Dr Jeff Weber, Moffitt Cancer Center, Tampa, Florida, USA, ANTI-CTLA-4: A new immunological approach on ecancer tv. Cancer journal: online cancer news, clinical oncology research, cancer information and latest cancer studies - open access cancer journal: ecancermedicalscience | ecancermedicalscience

Take Care,

Jimmy B

A Roller Coaster Chase for a Cure, Dr. Keith Flaherty Story..Melanoma..Jim Breitfeller

A Roller Coaster Chase for a Cure, Dr. Keith Flaherty Story

Published: February 21, 2010

PHILADELPHIA — His patient, a spunky Italian-American woman in her 60s, was waiting in an exam room down the hall for the answer: Was the experimental drug stopping her deadly skin cancer?


THE INVESTIGATOR Dr. Keith Flaherty oversees the testing of a drug known as PLX4032 calling it the best hope against melanoma “because it is based on what makes cancer tick.”


But as Dr. Keith Flaherty read out the measurements of her tumors from the latest CT scan, he could not keep the distress from his voice.

“She’s worse,” he said to the clinical trial nurse at the University of Pennsylvania’s melanoma clinic.

Source:http://www.nytimes.com/2010/02/22/health/research/22trial.html?pagewanted=1

A Roller Coaster Chase for a Cure, Dr. Keith Flaherty Story


As you can read, The research doesn't happen over night. You need a clinical Researcher that believes in the science.

I myself believe in our approach in how to get the host's immune system to see the Melanoma Cancer tumor cells. I have pages of Universities, Hospitals and Drugs companies following my blog at one time or another.

I even got this note from a world renowned Clinical Researher:

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

I have seen this treatment work. Until we have a Clinical trial in place, we won't know what the response rate would be.

We need more Clinical Researchers and Oncologists willing to step and think outside the box. Follow their passion and gut feelings to pursue a CURE. I tip my Hat to Dr. Keith Flaherty. Thanks for thinking outside the box!!!



Melanoma and The Magic Bullet (Monoclonal Antibodies)



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~

Tremelimumab Shows Low But Durable Response Rate in Advanced Melanoma..Jim Breitfeller

Tremelimumab shows low but durable response rate in advanced melanoma
FEBRUARY 18, 2010

"NEW YORK (Reuters Health) - In a phase II trial in patients with advanced refractory or relapsed melanoma, tremelimumab (CP-675,206) showed a 6.6% objective response rate, with these responses lasting more than six months, a multinational group of researchers report in the February 1 issue of Clinical Cancer Research."

Source:http://www.curetoday.com/index.cfm/fuseaction/news.showNewsArticle/id/13/news_id/2350

Tremelimumab shows low but durable response rate in advanced melanoma


As you can see, the response rate is low as a monothrapy, but if you can get the tumors to shed antigentic proteins by combining with chemotherapy, irradiation and other molecules to stop the repair of the tumor Cell DNA, then you have antigens to present on the the (APCs) Antigen Presenting Cells. Interluekin-2 can be added at the end of the T-cell expansion to help grow and maintain the (CTLs) Cytotoxic T Lymphocytes.





adapted from Henry Stewart Talks by Jim Allison



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~

What do we Know about with Checkpoint Blockade in Cancer Immunotherapy?Melanoma,,Jim Breitfeller

TOPICS COVERED IN CHECKPOINT BLOCKADE IN CANCER IMMUNOTHERAPY

Activation of naive T-cells | CD28 and CTLA-4 | Differential regulation of T-cell responses | Responding repertoire | Biological role of CTLA-4 | Tumor-specific immune responses | Treg activity | CTLA-4/GVax | Immunotherapies | Conventional therapies | Ipilumumab | Clinical studies: melanoma | Reversible immune mediated toxicity


Slides
1. Introduction
2. Checkpoint blockade In cancer immunotherapy
3. Two signals are required for naive T cells activation
4. Many molecules shape the immune response
5. Functional asymmetry of CD28 and CTLA-4
6. Integration of TCR and costimulatory signals
7. Localization of CD28/CTLA-4 in migrating T cells
8. The movement of CD28 and CTLA-4
9. Do B7-1 or/and B7-2 dimerize?
10. B7-1 may dimerizes,while B7-2 appear monomeric
11. CD28 and CTLA-4 signaling complexes
12. Signaling processes on the T cell - APC junction
13. The role of CD28 and CTLA-4 cytoplasmic tails
14. Effect of agonists' strength on CTLA-4 localization
15. CD28 and CTLA- 4 trafficking
16. Differential regulation of T cell responses
17. CTLA-4 preferentially inhibits the best-fit response
18. Models for biological role of CTLA-4
19. How does CTLA-4 broaden responding repertoire?
20. Biological role of CTLA-4
21. Effect of CTLA-4 blockade
22. Effect of anti-CTLA-4 on transplantable tumor
23. Anti-CTLA-4 and GM-CSF synergise
24. Side effects following rejection of B16 melanoma
25. Effect of anti-CTLA-4/GVax
26. CTLA-4 has a cell-autonomous activity
27. Effect of exposure to anti-CTLA-4 in vivo
28. Effect of exposure to anti-CTLA-4 in vitro
29. Anti-CTLA-4 does not block Treg activity in vitro
30. Anti-CTLA-4/GVax increases Teff/Treg ratio
31. Summary: effective combinations of anti-CTLA-4
32. Chimeric murine CTLA-4 transgene
33. Effect of anti-CTLA-4 on MC38 tumor growth
34. MDX-010 (Ipilumumab)
35. Clinical response to a single dose of Ipilumumab
36. MDX-010-05 study design
37. Trial results: complete responder - patient 11
38. Example: CTLA-4 blockade effects on tumors
39. Reversible immune mediated toxicity
40. MDX010-020: Pivotal Phase III Trial
41. Autologous GVAX followed by MDX-010
42. Trial results: melanoma patient 15
43. Ovarian GVAX and Anti-CTLA-4 Ab - single dose
44. Reduction in tumor nodules following MDX-010 Rx
45. "Lupus-like" rash in ovarian cancer
46. Ovarian GVAX and Anti-CTLA-4 Ab effects
47. Research contributors
48. GVAX immunotherapy and Ipilimumab for HRPC
49. Trial results: PSA curves at dose-level 3
50. Trial results: bone scan improvement in patient 8
51. Checkpoint blockade works
52. Many questions still to be answered
53. Acknowledgements
54. Current lab members
55. END

Checkpoint Blockade in Cancer Immunotherapy


http://hstalks.com/lib.php?t=HST47.1385_1_3&c=252


Take Care,

Jimmy B

Cancer Immunotherapy: What Do We Know and How Did We Learn It?Melanoma..Jim Breitfeller

Steven A. Rosenberg

Surgery Branch, National Cancer Institute, Bethesda, MD, USA

"In the past two decades immunotherapy approaches have been shown to be effective for the treatment of selected patients with metastatic cancer. The administration of interleukin-2 or a monoclonal antibody against CTLA-4 can mediate regression of metastatic melanoma in about 15% of patients. The administration of in vitro expanded autologous anti-tumor T cells, plus IL-2, following a lymphodepleting chemotherapy results in objective regressions in 50% of patients with metastatic melanoma. In a recent trial adding total body irradiation to the preparative regimen, an objective response rate of 72% was seen including 32% of patients with a complete response, all but one ongoing beyond two years1,2. T cells capable of mediating these regressions have been used to identify dozens of human cancer antigens3. Recently gene therapy approaches that utilize the transduction of genes encoding anti-tumor T cell receptors has resulted in objective cancer regressions4,5. This latter approach is now being applied to the immunotherapy of patients with common epithelial cancers."


source:http://web.ncifcrf.gov/events/cancervaccine/ProgramBook.pdf


References
1.
Dudley, M.E., Wunderlich, J.R., Robbins, P.F., Yang, J.C., Hwu, P., Schwartzentruber, D.J., Topalian, S.L., Sherry, R., Restifo, N.P., Hubicki, A.M., Robinson, M.R., Raffeld, M., Duray, P., Seipp, C.A., Rogers-Freezer, L., Morton, K.E., Mavroukakis, S.A., White, D.E., and Rosenberg, S.A.: Cancer regression and autoimmunity in patients after clonal repopulation with anti-tumor lymphocytes. Science 298:850-854, 2002.
4
2.
Dudley, M.E., Yang, J.C., Sherry, R., Hughes, M.S., Royal, R., Kammula, U., Robbins, P.F., Huang, J., Citrin, D.E., Leitman, S.F., Wunderlich, J., Restifo, N.P., Thomasian, A., Downey, S.G., Smith, F.O., Klapper, J., Morton, K., Laurencot, C., White, D.E., and Rosenberg, S.A.: Adoptive cell therapy for patients with metastatic melanoma: Evaluation of intensive myeloablative chemoradiation preparative regimens. J. Clin. Oncol., 26:5233-5239, 2008.
3.
Rosenberg, S.A.: Progress in human tumour immunology and immunotherapy. Nature 411:380-384, 2001.
4.
Morgan, R.A., Dudley, M.E., Wunderlich, J.R., Hughes, M.S., Yang, J.C., Sherry, R.M., Royal, R.E., Topalian, S.L., Kammula, U.S., Restifo, N.P., Zheng, Z., Nahvi, A., de Vries, C.R., Rogers-Freezer, L.J., Mavroukakis, S.A., and Rosenberg, S.A.: Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314:126-129, 2006.
5.
Johnson, L.A., Morgan, R.A., Dudley, M.E., Cassard, L., Yang, J.C., Hughes, M.S., Kammula, U.S., Royal, R.E., Sherry, R.M., Wunderlich, J.R., Lee, C-C. R., Restifo, N.P., Schwarz, S.L., Cogdill, A.P., Bishop, R.J., Kim, H., Brewer, C.C., Rudy, S.F., VanWaes, C., Davis, J.L., Mathur, A., Ripley, R.T., Nathan, D.A., Laurencot, C.M., and Rosenberg, S.A.: Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 114:535-546, 2009


When you put together all that we know, Treg surpression,Anti-CTLA-4 Blockage and IL-2 growth factor, Oncologists have the tools to stabilize Melanoma. In some cases, they may have even cured Melanoma. Time will only tell.



Melanoma And the Magic Bullet, (Monoclonal Antibodies)



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~

Melanoma Drugs (BRAF Inhibitors) Have Unintended Effects in Some Tumors..Jim Breitfeller

Some patients with advanced melanoma have had dramatic responses to a new class of targeted drugs in early stage clinical trials. While the long-term effects of these drugs, called BRAF inhibitors, are not yet known, two reports suggest that these drugs may have unintended consequences in patients whose tumors lack mutations in the BRAF gene.

In separate studies, scientists in Great Britain and the United States tested the drugs in the laboratory to better understand how BRAF inhibitors behave in cells. To their surprise, the drugs actually spurred the growth of some tumors. The preliminary findings raise the possibility that certain patients should not receive BRAF inhibitors because the drugs could make their cancers worse.

Source:NCI Cancer Bulletin February


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~

Keeping the lid sealed on Medical Science to ensure its translation into Medical Practice..Melanoma..Jim Breitfeller

“To keep the lid sealed on this corruption of medical science—and to ensure its translation into medical practice—there is a complex web of corporate influence that includes disempowered regulatory agencies, commercially sponsored medical education, brilliant advertising, expensive public relations campaigns, and manipulation of free media coverage. And last, but not least, are the financial ties between many of the most trusted medical experts and the medical industry. These relationships bear a remarkable resemblance to the conflicts of interest the Securities and Exchange Commission recently brought to a halt after learning that securities analysts were receiving bonuses for writing reports that drove up stock prices with the intent of bringing in more investment banking business.”


Quoted from:
Overdosed America by John Abramson MD, page 9

Source: http://www.olccme.com/managingmelanoma/

Is it one Big Infomercial? Commercial Support of this Educational Meeting?

Financial ties between many of the most trusted medical experts and the medical industry.

And Bristol Myer Squibb can’t open Compassionate Drug use to the Critically Ill Patients.

Who is watching the Hen House? What happen to the code of ethics?





Disclosure
DISCLOSURE STATEMENT AND RESOLUTION OF ANY CONFLICTS OF INTEREST
Not an official event of the ASCO Annual Meeting. Not sponsored or endorsed by ASCO or The ASCO Cancer Foundation.
In accordance with the Accreditation Council for Continuing Medical Education (ACCME) Standards for Commercial Support, all educational programs sponsored by the Oncology Learning Center (OLC) demonstrate fair balance, complete independence from any commercial supporters, objectivity, and scientific rigor. All faculty, authors, editors, OLC staff and planning committee members participating in an educational activity who are in control of content or in communication with faculty are required to disclose any relevant financial interest or other relationships with the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial services that are discussed in an OLC educational activity. All disclosures will be made available to all activity participants prior to the conduct of its educational activity. In addition, all conflicts of interest will be resolved prior to the conduct of its educational activity.

DISCLOSURE OF UNLABELED USE

This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The Oncology Learning Center does not recommend the use of any agent outside of the labeled indications.

The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the Oncology Learning Center. Please refer to the official prescribing information for each product for discussion of approved indicated, contraindications, and warnings.

DISCLAIMER

Participants of OLC's educational activities have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development and practices. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient's conditions and possible contraindications on dangers in use, review of any applicable manufacturer's product information, and comparison with recommendations of other authorities.
In a related Story
FBI: Syracuse man downloaded Bristol-Myers Squibb's process for making cutting-edge cancer drug
By Douglass Dowty / The Post-Standard
February 04, 2010, 5:47PM

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

Syracuse, NY -- Among the trade secrets a Syracuse man took from Bristol-Myers Squibb were steps to produce a multi-million dollar drug under development to treat a deadly form of cancer, FBI agents said.
Shalin Jhaveri, 29, was arrested Tuesday after a two-month investigation by the company and the FBI. He was living in an apartment on East Water Street in Hanover Square.
Jhaveri was in a management training program at Bristol’s East Syracuse facility, which develops cutting edge drugs known as biologics, federal authorities said. While there, he downloaded confidential procedures for biologics that he e-mailed to a potential business partner in his native India, prosecutors said.

Jhaveri’s ultimate goal was to start his own biopharmaceutical company, Cherish Bio Services, in India, according to court documents. His business partner was a potential investor who FBI agents recorded talking to Jhaveri on Jan. 25, court documents show.
During that conversation, Jhaveri told the partner he had set up a Gmail account and sent procedures for making “Anti-Human CD137 Monoclonal Antibody,” a biologics drug for patients with malignant melanoma. The rare skin cancer has no proven cure in its advanced stages.

Human CD137 (4-1BB) is expressed on activated T cells within 24-48 hours of activation.

That’s why the drug is a potential blockbuster for Bristol that could bring in $1 billion a year if it reaches mass production, said a stock analyst who monitors Bristol’s products. Right now, the drug is in early stages of clinical testing.

“It’s a big deal,” said Les Funtleyder, a health care strategist with Miller Tabak & Co. “If it were to succeed, it could be a blockbuster.”
He said biologics use animal cells to create pharmaceuticals, which cost a lot of money to produce and test. He estimated that Bristol could have spent up to $500 million developing this drug, BMS-663513, and others like it.

“It’s not easy to do,” he said. “It takes a lot of time and money.”
Bristol officials, who declined comment for this story, began tracking Jhaveri’s actions in December after finding documents on his work laptop that included an application to the government of India to start his own biopharmaceutical company, court records show. Computer specialists found Jhaveri had downloaded 45 gigabytes of information onto an external drive.

Soon afterward, authorities recorded a phone conversation Jhaveri had with the business partner from India. Their correspondence led to a meeting in Syracuse at the Renaissance Hotel on Tuesday, according to court documents.

There, Jhaveri showed the partner virtually all the “Standard Operating Procedure” documents kept at the East Syracuse facility, court records state. These included the trade secrets for the melanoma drug, among many others. All together, Jhaveri had 1,327 standard operating procedures, all of which were confidential, court records state.

An FBI agent confronted Jhaveri, who admitted to sending the confidential drug information and taking the standard operating procedures without authorization, court documents state.

Jhaveri, who holds a Ph.D. and was a former graduate research assistant at Cornell University, is currently in federal custody without bail. A detention hearing is scheduled for Monday in Syracuse.

Source:http://www.syracuse.com/news/index.ssf/2010/02/fbi_sryacuse_man_downloaded_st.htmlDisclosure

As you can see, Bristol Meyer Squibb is infiltrated with corruption.




Take Care,

Jimmy B

BioLegends,,Immunology Pathways,and Intracellular Signaling Pathways..Melanoma..Jim Breitfeller

BioLegends of the Cancer Pathways,Immunology Pathways,and Intracellular Signaling Pathways
BioLegend

Posted using ShareThis

The Orchestration of an Immune Response Unrehearsed! Melanoma..Jim Breitfeller

February 4 is World Cancer Day—a global day of awareness created by the International Union Against Cancer. With cancer set to become the #1 killer in the world this year, the day brings us together to highlight the growing personal and economic impact of the disease. On this day it’s critical that each organization—and each individual—share responsibility for sending a powerful message about cancer prevention.





















Melanoma And the Magic Bullet (monoclonal Antibodies



Take Care,

Jimmy B

Is Bristol Myer Squibb adhering to the Phama Code? Do they have a code of Ethics?Melanoma..Jim Breitfeller

Is Bristol Myer Squibb adhering to the Phama Code? Do they have a code of Ethics?

The Pharmaceutical Manufacturing and Research Association has a code of marketing practice, but ethics isn't mentioned.

PhRMA Code
The Pharmaceutical Research and Manufacturers of America (“PhRMA”) represents research-based pharmaceutical and biotechnology companies. Its Code on Interactions with Healthcare Professionals (“the PhRMA Code”) reinforces our intention that our interactions with healthcare professionals are to benefit patients and to enhance the practice of medicine.

Are the Melanoma Patients that BMS tuned away due to the closing of the compassionate drug use benefiting? I don’t think so. I believe BMS is lining their pockets.

BMS says they are adhering to the PhRMA Code. What do you think?


I think it is time to vote with our feet. When and if generics comes out, I will be the first in line to get generics.

Since they have no loyalty to the patients why should we have loyalty to them?. They just want us to get hooked up with their drug and not the cheaper alternative.

Obligations of truthfulness and integrity — minimal criteria for any company that seeks to do good, as all health care companies must — are especially powerful, and serve as the cornerstones for successful organizations.

Individual drug companies also have codes of marketing practice, but no codes of ethics.


. Ethical guidelines are important to physicians because their patients trust them to do what's best for them. Ethics is important to industry primarily because it fosters trust.

I for one have lost that trust of the industry, in particular, Bristol Myer Squibb.

The pharmaceutical industry needs the high road, not the low one. Industry should not make the mistakes of managed care. Managed care is not proud of ethics, imbued with the public trust or even respectful of doctor-patient relationships. Industry has a chance to speak about ethics and to let patients know what it stands for. It cannot afford to do anything else.

Bristol Myer Squibb, It is time to incorporate a code of ethics. Show Your True Colors



Take Care,

Jimmy B

Bristol Meyer Squibb, Where do you draw the Line in the Sand?Melanoma ..Jim Breitfeller

Bristol Meyer Squibb, Where do you draw the Line in the Sand?



“What I found over the next two and a half years of "researching the research" is a scandal in medical science that is at least the equivalent of any of the recent corporate scandals that have shaken Americans' confidence in the integrity of the corporate and financial worlds. Rigging medical studies, misrepresenting research results published in even the most influential medical journals, and withholding the findings of whole studies that don't come out in a sponsor's favor have all become the accepted norm in commercially sponsored medical research. To keep the lid sealed on this corruption of medical science—and to ensure its translation into medical practice—there is a complex web of corporate influence that includes disempowered regulatory agencies, commercially sponsored medical education, brilliant advertising, expensive public relations campaigns, and manipulation of free media coverage. And last, but not least, are the financial ties between many of the most trusted medical experts and the medical industry. These relationships bear a remarkable resemblance to the conflicts of interest the Securities and Exchange Commission recently brought to a halt after learning that securities analysts were receiving bonuses for writing reports that drove up stock prices with the intent of bringing in more investment banking business.”

Quoted from:

Overdosed America by John Abramson MD, page 9


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?

Where do you draw the Line in the Sand?

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:



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


Estimated Enrollment:30
Study Start Date:February 2009
Estimated Primary Completion Date:
February 2013 (Final data collection date for primary outcome measure)ClinicalTrials.gov Identifier:NCT00836407

A Phase I Study of Repetitive Dosing of Anti-CTLA-4 Antibody (MDX-010) in Combination With GM-CSF in Patients With Metastatic, Androgen-Independent Prostate Cancer


Estimated Enrollment:36
Study Start Date:November 2009
Estimated Primary Completion Date:
November 2013 (Final data collection date for primary outcome measure)



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 as the STRING OF PEARLS.

.And the FDA has turned a blind Eye and gave it its unoffical approval to allow this to happen.
Where are the comsumers being protected. Without the patients, Bristol Meyer would have no trials. Very STRANGE BEDFELLOWS TO SAY THE LEAST.



Take Care,

Jimmy B

Why Can't Bristol Meyer Squibb share with the Patients?Melanoma..Jim Breitfeller

Why Can't Bristol Meyer Squibb share with the Patients?

We the patients take all the risk and become their consumer base. Or should we just say No!!!!
It is not like they are short on Cash.

James M. Cornelius, I challenge you to do what is ethically right and reinstate the compassionate drug (Ipilimumab)use for the critically ill patients of our nation. Stop raping them blind.

"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~

It is all Lip service. A con Job!!!!! They don't care about the patients that don't qualify for their trials. They have no compassion whatso ever.

Bristol CEO ‘Out Hunting’ for Deal With $10 Billion



By Shannon Pettypiece

Jan. 28 (Bloomberg) -- Bristol-Myers Squibb Co. Chief Executive Officer James M. Cornelius said his company is “out hunting” for deals and has $10 billion in cash.

Bristol-Myers’s acquisition and licensing efforts will be the same in 2010 as they were last year when the New York-based company acquired Medarex Inc. and split off its Mead Johnson Nutritional Co., Cornelius said today in a conference call with reporters. He added that his company doesn’t “have a ‘for sale’ sign up,” an answer to speculation from analysts that Bristol- Myers is a potential takeover target.

Cornelius needs to speed new drugs to market to fill a revenue hole Bristol-Myers will face in 2012 when generic copies of its top-selling Plavix blood thinner become available. He has been narrowing the company’s focus to biotechnology and pharmaceuticals and disposing of other operations. Since 2007, Bristol has acquired nine companies developing treatments for cancer, immune disorders and pain.

“There is $10 billion of real cash in the bank so we have the flexibility and the speed to get these deals done,” he said. “We are out hunting and we will see what we can get done.”

Source:http://www.bloomberg.com/apps/news?pid=20601103&sid=aqBFvInwsJ3Y

It is time to stand up to the Global Pharmaciticals.

Please sign the petition.

Thank you


Take Care,

Jimmy B

I thought you would like to Know this. BMS..Melanoma..Jim Breitfeller

IPILIMUMAB TUMOR PLANNING(Job Number: 1000235)

Description

This candidate will be a member of the Ipilimumab Global Marketing team. Major responsibilities will include - Leadership of the prostate cancer program oPositioning work o Label Optimization (Collaboration with the clinical, medical and regulatory team to ensure commercial success) o Patient Insight work o Tumor Strategy Group Member (Opportunity to provide input to franchise strategy: Future market Map, Scenario Planning, CI readiness) Leadership of the pancreatic program o Label Optimization (Collaboration with the clinical, medical and regulatory team to ensure commercial success) o Preparation for key DP discussions o Choices 1-5 o Collaboration with franchise GI tumor lead Management of innovative virtual insight exchange program for all indications Key commercial member to the future tumor planning for the brand o Lead commercial tumor deep dives for assessment of attractiveness Management of the Competitive Intelligence Plan for non-Melanoma indications Collaboration with advertising agency, medical education agency and interactive agency to drive performance of projects Collaboration with SPDA on Forecasting for LCM opportunities. This position will work closely with the melanoma team to insure integration of learnings is rapidly applied and appropriate market development is being identified.

Qualifications

2 plus years of Global Marketing and operational Marketing experience at the D7 level. MBA or equivalent. Understanding of the oncology marketplace and demonstrated ability to learn about different tumor types (preferable). Experience in communication and leadership of teams across various functions. Ability and desire to analyze clinical data. Strong interpersonal skills and ability to motivate and build alignment across matrix teams. Demonstrated ability to effectively and efficiently drive performance within a matrix organization. Analytical thinking and innovative approach to problem solving. Experience in strategic thinking and executing against plans. Ability to demonstrate expertise in marketing analytics and market, customer & competitive insight

Job Function: Marketing
Primary Location: NA-US-NJ-Princeton

It is not about the patient, it is about how they can leverage this drug in the marketplace

The results were so startling that researchers decided to release details of the two cases before the drug trial – in which the patients took part – was complete. Doctors said their progress had exceeded all expectations. The men were treated at the Mayo Clinic in Minnesota in the US, one of the top medical centres in the world.

Dr Eugene Kwon, the urologist who was in charge of their treatment, compared the results to the first pilot breaking the sound barrier.

"This is one of the Holy Grails of prostate cancer research. We have been looking for this for years," he said.

Ipilimumab is one of a class of drugs called monoclonal antibodies, which stimulate the body's own immune system to fight disease. The experimental treatment is being developed by Bristol-Myers Squibb and Medarex, a US biotech company. The drug is being trialled on malignant melanoma, the most serious form of skin cancer, Hodgkin's disease, lung cancer and prostate cancer. Studies are most advanced in melanoma, where it has been shown to prolong survival in patients with advanced forms of the disease. In the Mayo Clinic study of prostate cancer, researchers say that standard hormone treatment ignited the immune response, and adding ipilimumab was like "pouring gasoline on the pilot light".

Take Care,

Jimmy B