A few days ago Dendreon reported great news in the battle against prostate cancer.

The median overall survival benefit of PROVENGE in the Phase 3 IMPACT Trial was estimated to be 7.8 months.

Care To Live has always believed Provenge should have been approved way back in May 2007. We were delighted when it finally was approved in May of 2010, albeit 3 years after it should have been due to the FDA’s malfeasance. This latest news further fortifies the 2007 survival results.

Dendreon presented the following data to the American Society of Clinical Oncology 2012 Genitourinary Cancers Symposium in San Francisco, California.

• “An Analysis to Quantify the Overall Survival (OS) Benefit of Sipuleucel-T Accounting for the Crossover in the Control Arm of the IMPACT Study,” abstract #144 - Thursday, February 2, 2012.
• “Sipuleucel-T Product Characterization Across Different Disease States of Prostate Cancer,” abstract #42 - on Thursday, February 2, 2012.
• “Neoadjuvant Sipuleucel-T in Patients with Localized Prostate Cancer: Immune Responses in Prostate Tumor Tissue,” abstract #181 - on Friday, February 3, 2012.
• “Evaluation of Immune Activation Following Neoadjuvant Sipuleucel-T in Subjects with Localized Prostate Cancer,” abstract #178 - on Friday, February 3, 2012.

“For the past 15 years, Dendreon has been focused on changing the way that cancer is treated,” said Mark Frohlich, MD, chief medical officer. “These latest findings continue to support the overall survival benefit of PROVENGE, and its mechanism of action. They provide a strong rationale for examining PROVENGE earlier in prostate cancer.”

Abstract #144: An Analysis to Quantify the Overall Survival (OS) Benefit of Sipuleucel-T Accounting for the Crossover in the Control Arm of the IMPACT Study

The Phase 3 IMPACT trial included a crossover design that allowed patients who were randomized to the control arm and experienced disease progression the opportunity to participate in an open label Phase 2 protocol to receive APC8015F, an investigational autologous cellular immunotherapy made from cells that were cryopreserved at the time the control was manufactured. As a result, 109 out of the 171 control patients (64%) received APC8015F.

In this exploratory analysis, researchers used a rank-preserving structural failure time (RPSFT) model, to quantify how treatment with APC8015F might have impacted the overall survival of the Phase 3 IMPACT trial by adjusting for the positive treatment effect of APC8015F in the control arm. The previously published intent to treat analysis, which is described in the Food and Drug Administration (FDA) approved prescribing information for PROVENGE, did not account for cross-over and demonstrated a 4.1 month median survival benefit (HR=0.775, 95% CI: 0.614, 0.979). Using the RPSFT model, and assuming that APC8015F was equally effective as PROVENGE, the median overall survival benefit of PROVENGE in the Phase 3 IMPACT trial was estimated to be 7.8 months, had there been no cross-over to APC8015F (HR=0.60, 95% CI: 0.41, 0.95).

“The results of this exploratory analysis are encouraging,” said Chadi Nabhan, MD, Oncology Specialists S.C., Lutheran General Hospital Cancer Care Center. “These data continue to support the use of PROVENGE as an important and compelling treatment option for men with certain types of advanced prostate cancer.”

Abstract #42: Sipuleucel-T Product Characterization Across Different Disease States of Prostate Cancer

An exploratory analysis of several PROVENGE clinical trials (IMPACT, ProACT, OpenACT, and NeoACT) examined the product characteristics of PROVENGE comparatively across different disease states (asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (mCRPC), and mCRPC, and neoadjuvant).

The pattern of antigen presenting cell (APC) activation, as measured by upregulation of CD54, was consistent across all of the clinical trials, with increased APC activation at the second and third PROVENGE treatments relative to the first. The second and third dose of PROVENGE also consistently showed enhanced expression of lymphocyte activation markers and cytokines. APC activation tended to be more robust in earlier disease states, as evidence by increased cumulative fold increase in CD54 upregulation in neoadjuvant patients (35.5) relative to asymptomatic or minimally symptomatic mCRPC (28.7) and mCRPC patients (21.8; P < 0.0001).

“I find these data to be very compelling — this exploratory analysis provides insight into the biological effect of PROVENGE and immunologic activity across different stages of prostate cancer,” said Eric Small, MD, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center. “These data suggest that PROVENGE should be studied in earlier stages of disease, when patients have less tumor burden.”

Abstract #181: Neoadjuvant Sipuleucel-T in Patients with Localized Prostate Cancer: Immune Responses in Prostate Tumor Tissue

A Phase 2 study, called NeoACT (NEOadjuvant Active Cellular immunoTherapy), evaluated treatment with PROVENGE prior to radical prostatectomy in patients with localized prostate cancer. PROVENGE is not currently indicated in this setting. This analysis assessed the presence of lymphocytes by immunohistochemistry (IHC) in radical prostatectomy tissue following treatment with PROVENGE and compared it to prostate biopsy tissue obtained prior to treatment.

At the time of abstract submission, IHC analysis had been completed in 19 patients. Significant increases ( > 2-fold) in CD3⁺ and CD4⁺ T-cells populations were observed at the tumor rim between the interface of benign and malignant tissue when compared with the pretreatment biopsy tissue (ANOVA post hoc Newman-Keuls test: P=0.0002, both).

“This analysis of prostate tissue from patients participating in the Phase 2 NeoACT trial demonstrated increased T-cell activity at the rims of prostate cancer tumors, which provides important support for PROVENGE’s intended mechanism of action,” said Lawrence Fong, MD, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center.

Abstract #178: Evaluation of Immune Activation Following Neoadjuvant Sipuleucel-T in Subjects with Localized Prostate Cancer

In addition, a second analysis of the Phase 2 NeoACT study evaluated immune activation in PROVENGE for patients with localized prostate cancer treated prior to surgery. This analysis evaluated the cellular composition and APC activation of the product both prior to and after the culture with the recombinant fusion protein PA2024, consisting of prostatic acid phosphatase (PAP) and granulocyte macrophage colony stimulating factor (GMCSF).

The Phase 2 NeoACT study enrolled 42 patients and 38 received all three infusions of PROVENGE. Consistent with past findings in PROVENGE mCRPC trials, CD54 upregulation (APC activation) was greater at the second and third PROVENGE infusions. The expression of early T-cell activation markers (CD134, CD137, CD278 and CD279) was increased in cells obtained after the first infusion of PROVENGE, and then further increased post-culture with PA2024. Also observed was a progressive increase in memory B-cells (CD20⁺CD27⁺IgD^-CD86⁺; pre- and post-culture) and activated mature B-cells (CD20⁺CD27⁺IgD⁺CD86⁺; post-culture) following the first infusion of PROVENGE. Activated T-cell-associated cytokines were significantly elevated (TNF-α, P < 0.001; IFN-γ, P < 0.001; and IL-2, P < 0.001) in the second and third PROVENGE doses.

Initial results from the trial indicate neoadjuvant treatment with PROVENGE showed evidence of immune system activation that included APCs, memory and activated mature B-cells, and both CD4⁺ and CD8⁺ T-cells. This analysis supports further studies to evaluate the use of PROVENGE in localized prostate cancer.

About the IMPACT Trial

IMPACT (IMmunotherapy for Prostate AdenoCarcinoma Treatment) is a 512-patient, multi-center, randomized, double-blind, controlled study evaluating men with asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. The primary endpoint was overall survival.

Initial results from the IMPACT study found PROVENGE extended median survival by 4.1 months compared to control (25.8 months vs. 21.7 months) and reduced the risk of death by 22.5 percent compared to control. Control used in the trial was non-activated autologous peripheral blood mononuclear cells. The survival benefit associated with PROVENGE was observed consistently across multiple patient subgroups, including those with prognostic factors known to be adversely correlated with overall survival, such as PSA, LDH, alkaline phosphatase, number of bone metastasis, Gleason score, performance status, and presence of pain.

Adverse events more commonly reported in the PROVENGE arm of this study included chills, fever, headache, influenza-like illness, muscle aches, hypertension and groin pain.

PROVENGE Indication and Important Safety Information

PROVENGE is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer.

PROVENGE is intended solely for autologous use and is not routinely tested for transmissible infectious diseases.

The safety evaluation of PROVENGE was based on 601 prostate cancer patients in four randomized clinical trials who underwent at least one leukapheresis. The most common adverse events (incidence greater-than or equal to 15%) are chills, fatigue, fever, back pain, nausea, joint ache, and headache. Serious adverse events reported in the PROVENGE group include acute infusion reactions (occurring within 1 day of infusion) and cerebrovascular events. In controlled clinical trials, severe (Grade 3) acute infusion reactions were reported in 3.5% of patients in the PROVENGE group. Reactions included chills, fever, fatigue, asthenia, dyspnea, hypoxia, bronchospasm, dizziness, headache, hypertension, muscle ache, nausea, and vomiting. No Grade 4 or 5 acute infusion reactions were reported in patients in the PROVENGE group.

To fulfill a post marketing requirement and as a part of the company’s ongoing commitment to patients, Dendreon will conduct a registry of approximately 1500 patients to further evaluate a small potential safety signal of cerebrovascular events. In four randomized clinical trials of PROVENGE in prostate cancer patients, cerebrovascular events were observed in 3.5% of patients in the PROVENGE group compared with 2.6% of patients in the control group.

For more information on PROVENGE, please see the full prescribing information at http://www.provenge.com or call 1-877-336-3736.

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Ted Girgus, an energetic man who stood up and fought as hard as he could for what he believed in, lost his battle with prostate cancer on Wednesday, November 23rd.

Ted had hoped to be on Provenge way back in 2007.

Here’s Ted protesting for Provenge approval back in 2008:

http://www.youtube.com/watch?v=6Q0uQAL_YDA

Ted could have been rebuilding his immune system all these years had it not been for FDA illegally leaked letters disparaging Provenge right after the Provenge Advisory Committee voted to support approval of Provenge. The panelists voted Provenge SAFE by a count of 17 to 0 and voted Provenge showed SUBSTANTIAL EVIDENCE OF EFFICACY by a count of 13 to 4.

A severely conflicted doctor, namely, Dr. Howard Scher, working out of Sloan Kettering in New York City, spearheaded the delay on many fronts. It is Care To Live’s contention that Scher helped write a letter, along with three other doctors, on behalf of Cougar Biotechnology before the March 29, 2007 panel hearing, in which they begged the FDA not to approve Provenge. At that time Scher did not disclose that he was leading a Novacea Asentar trial and a Cougar Abiraterone trial, both products in competition with Provenge. This explains why he was so active in fighting against Provenge approval during the hearing. After the hearing he worked with Alison Martin from NCI on a letter that was illegally leaked to The Cancer Letter by the FDA. The fact that the Food and Drug Administration (FDA), the National Cancer Institute (NCI), the Department of Justice (DOJ), and Congress, all allowed this malfeasance with impunity, while lives like Ted’s were hanging in the balance, is as despicable an act as any for agencies that supposedly are serving the public.

Ted greatly appreciated Care To Live’s fight for Provenge’s approval. He and his family fought right alongside us. Ted remains forever an exemplary American citizen despite the fact that our government, paid for by his hardworking tax dollars, betrayed him.

Here is an excerpt from the last e-mail Ted wrote to CTL:

Hi Gang,

I’ve been keeping a low profile for awhile due to my new prognosis. My doctors have told me that the cancer has affected my kidneys. I’ve been told that I have about 2 months to live. I will contact the Provenge Site where I live but I think I’m past the point that they will accept me.

I want you all to know how special you have made my life and the purpose you have given me and my family.

The Scriptures tell us it’s not how we start our lives that’s important, it how we end it.

You have filled me with strength and purpose and for that I will always be grateful.

God Bless You All and I know I will see you in heaven!!!

Ted

May you rest in peace, Ted Girgus. Thanks for all you did for Care To Live. You were instrumental in the eventual approval of Provenge, and all cancer patients throughout the world owe you a debt of gratitude.

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With our deepest condolences we mourn the loss from prostate cancer, June 2, 2011 at 85 years of age, of one of Care To Live’s fiercest warriors during our battle for Provenge’s approval.  We never did, nor could we, thank him enough for all his help. Sometimes with death there is a revisiting of the person, and we welcome this opportunity to bring you Charles A. Reinwald the man, and his unique and incredible cancer foundation, with its focus on healing cancer, both medically and holistically.

A link to his website has always been right up there, on the top of our home page. Please add it to your ‘to do’ list. If you are a cancer patient, the Cancer Cure Coalition should be your first line of defense.

http://www.cancercurecoalition.org

Cancer Cure Coalition Mission Statement

http://www.cancercurecoalition.org/mission.html

Charles A Reinwald Biography

http://www.cancercurecoalition.org/board.html

Charles became a member of Care To Live early on. He was a great advocate of strengthening the immune system through diet and lifestyle changes, as well as medicine. Throughout the years Charles offered us advice, and support. He was fighting many wars, on many cancer fronts, but was never too tired to write one more letter or one more article, or to offer words of encouragement in our darkest hours, when we needed them most.

Charles was a rarity today. A true patient advocate, not beholden to any corporate or financial conflicts of interests.  He was not an investor in Dendreon which frustrated the likes of those reporters whose deviant agendas were to erroneously portray Provenge as ineffectual, such as Matthew Herper of Forbes Magazine.

A brilliant man, he strove to understand health and wellness better, utiliizing his vast talents to educate and share what he learned with others. That is what made him truly stand out from the pack.

Care to Live literally stood shoulder to shoulder with Charles at our Rockville, Maryland FDA protest on September 18, 2007. He was one of our keynote speakers.

Charles A. Reinwald lives on in the families who will receive Provenge, those patient advocate and those with cancer whose lives he touched directly, his wife, his children, several of whom attended our Provenge 10 city rally in Cleveland in 2008, his grandchildren, and through his wonderful Cancer Cure Coalition Foundation.

I strongly urge people to send donations to:

The Cancer Cure Coalition
305 Beach Road, Suite 204
Tequesta, FL 33469

Telephone: (561) 747-2127

a 501 (C) (3) tax exempt charitable organization. Your donations are tax deductible pursuant to the Internal Revenue Code.

* * * * *

In February 2008 Mr. Reinwald took the FDA to task in this press release.

http://www.reuters.com/article/2008/02/21/idUS136546+21-Feb-2008+PRN20080221

Cancer Cure Coalition Proposes Major Changes at the FDA

Thu Feb 21, 2008 7:45am EST

PALMS BEACH GARDENS, Fla., Feb. 21 /PRNewswire/ -- Flawed policies and bad

decisions at the FDA have contributed to an escalation of the cost of clinical

trials which now take an average of one billion dollars and require 10 years

for approval. This has delayed and even prevented the availability of many Continue Reading RIP Charles A. Reinwald — Cancer Cure Coalition Founder »

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Dear CMS,

Please consider first and foremost the men and the families who love them. These are the true beneficiaries of the Provenge Medicare coverage. To you they may be portrayed as points on a graph, but to us, each and every one of these men, matter greatly. We call them Dad, Grandpa, Son, Brother and Husband.

During the approval and now coverage process, we have experienced moments of extreme joy and devastating heartbreak. The almost five year old continuing Provenge saga, ongoing since Dendreon first filed the clinical portion of their Biologics License Application with the FDA in 2006, has ended up on your doorstep to make a coverage determination by June 30. So many of our men’s hopes and health are now riding on you.

We at Care To Live would like to make clear to CMS, FDA, NCI and all the other government agencies peripherally involved, that this process that Provenge and other treatments go through is much too long and much too arduous for the patients awaiting treatment. Serious consideration must be given to find ways to get these exciting new treatments to the patients who are without viable alternatives to death, sooner, including passage of the Abigail Alliance sponsored Access Act.

The FDA in particular, needs to help bring treatments for late stage disease, like late stage prostate cancer, to the patients earlier. During the Provenge approval process, the FDA and the NCI sadly acted as patient adversaries and barriers, instead of the bridge that we were promised.

Within CMS’ own walls, mistakes were made. We hope you will strive to avoid these careless actions in the future. Never should safety and efficacy, already put through a long and laborious FDA review process, ever be evaluated by your agency. If you decide to evaluate a treatment based upon your stated intentions, such as uniformity of coverage and classification of reimbursement, then you must make it very clear at the outset that this is your intention.

CMS lacks authority to re-evaluate data provided by the FDA for a treatment’s safety and efficacy. Such action is particularly ill conceived when it is a treatment for late stage cancer. Without fast action by Dendreon, patient advocates, and several Congressmen, many more men may have been denied treatment. Total catastrophe was averted but not before your agency came close to creating chaos as seen through the eyes of many patients, some of whom urged Congress to get involved.

This should never be allowed to happen again.

Despite what some have said in these comments and elsewhere, making late stage prostate cancer patients out to be sick old men, that is just plain wrong. Most are still active, vital people, with no outward signs of disease. Some are still quite young, and all, if left untreated, will die too early of a very painful disease.

We are not about to let that happen. Care To Live Continue Reading Care To Live Submits Moment of Silence to CMS »

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Human Health and Resources (HHS) transparency rules differs greatly between divisions. Center for Medicaid and Medicare (CMS) has been forthcoming with our Freedom of Information (FOIA) requests, while the Food and Drug Administration (FDA) and the National Cancer Institute (NCI) continue stalling. 

Read more at Pharmalot http://www.pharmalot.com/2011/04/the-fda-conflicts-of-interest-provenge-e-mails/

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Click Here >> to go to the CMS Comment Page

The April 29, 2011 Deadline is fast approaching. Take Nothing for granted.

Please take a moment to write a sentence or two to the Centers for Medicaid and Medicare (CMS) requesting them to continue providing coverage for Provenge, the FDA approved immunotherapy for late stage prostate cancer. It is a non toxic, non invasive FDA approved treatment, safer and more effective than anything that has been previously approved.

1 in 6 men get prostate cancer in their lifetimes. 30,000 a year go on to die from it. Provenge is the first approved treatment of its kind, which utilizes your own immune system to fight off the cancer.

In order to post, you must first open the CMS PHI Posting Policy link and then  remember to click the box below it:

Thank you for your prompt attention to this matter as this is time sensitive.

PS: If you have friends that will help, please email and forward. TIA

http://caretolive.com/Click Here >> on the CMS Comment Page to comment on the Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer (00422N).

Care To Live urges all of its friends and members to post a comment on the Centers for Medicare & Medicaid Services (CMS) web page encouraging them to support coverage of Dendreon’s Provenge.

Thank You,

Rory Kearney
President
Care To LIve,
a not for profit corporation

View Public Comments CAG-00422N  Comment Period: 03/30/2011-04/29/2011

http://www.cms.gov/medicare-coverage-database/details/nca-view-public-comments.aspx
?NCAId=247&ExpandComments=n&ver=11&NcaName=Autologous+Cellular+Immunotherapy+Treatment+of+
Metastatic+Prostate+Cancer&DocID=CAG-00422N&SearchType=
Advanced&bc=IAAAABAAEAAA&

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Great news from Dendreon today!

The FDA finally approved the remaining 75% of treatment stations at their New Jersey plant that manufactures Provenge.

This will quadruple their manufacturing capability and greatly help to alleviate some of the current supply/demand problem.

Two more plants in Los Angeles and Atlanta are also expected to be able to begin production in the near future.

Care To Live along with thousands of Patients, Urologists and Oncologists are thrilled that doctors will now be able to treat thousands more men with Provenge, however we will not sleep well until all the men who need Provenge can get it.

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Today CTL received an interim response to its two previous FOIA request made to CMS. The documents were retrieved upon a search performed by Dr Louis Jacques. We received 258 pages of which 74 pages were redacted under claimed exemptions of FOIA (5 U.S.C. 552 (b)(2), (b)(5) and (b)(6)).

Although the pdf’s are not in 100% chronological order it is probably easiest to comprehend each of the 5 individual pdfs, from back to front.

1-cms-foia-0221.pdf

2-cms-foia-02211.pdf

3-cms-foia-02-21.pdf

4-cms-foia–02-21.pdf

5-cms-foia-0221.pdf

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Matthew Herper, a writer for Forbes magazine and Forbes.com, has a biased, one-directional view of Dendreon’s Provenge, the first and only FDA-approved immunotherapeutic treatment for men with late stage prostate cancer. He continues to trip over his own feet in his attempts to lower the boom on Dendreon and Provenge. Over the past several years he even has attacked Care To Live, a prostate cancer patient advocacy group.

Mr. Herper could care less about the 30,000 men dying each year from an excruciatingly painful disease. He could care less about hurting a company financially that is attempting to cure not just prostate cancer, but many other forms of cancers as well. And he could care less about uncovering the malfeasance at the FDA Continue Reading Race To Undo The Cure »

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Care To Live, a not for profit corporation, tried to work with the Centers for Medicare and Medicaid Services (CMS) to avoid litigation in regards to CTL’s two FOIA requests but CMS gave no response. CTL’s Attorney, Kerry M. Donahue, had sent this letter to CMS inquiring about the requests:

kerrydonahuecmsletter.pdf

Once CMS did not respond, Kerry commenced litigation on CTL’s behalf on December 10, 2010:

ctlcmslitigationfile.pdf

Read more below at Ed Silverman’s Pharmalot site

Now, The Provenge Activists Are Suing Medicare

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