Cancer Drugs Now!

The Washington Post of May 31st reported that the FDA had adopted a new rule to allow approval of antiterrorism vaccines based upon ANIMAL STUDIES alone.

This is a double standard because a lymphoma vaccine was developed by Dr. Ron Levy at Stanford, in 1986. This vaccine has been extremely effective in HUMAN trials since 1992—yet it is still not available to patients. In a phase II trial conducted by the National Cancer Institute (NCI), the Levy vaccine delivered extraordinarily long remissions to 90% of trial subjects, who had first been put in remission. As of January 2001, 77% of these were still disease free—for up to 74 months.

At the time of this writing, 48 months have passed since this study was published. During that time, 98,700 persons have died from non-Hodgkin's lymphoma—or from its toxic treatments. Yet, patients still cannot get the Levy vaccine unless they enter a new study of the Levy vaccine, launched by the NCI. This trial is randomized trial and has at least 5 years more to run. The object is to scientifically “prove, once and for all” that vaccines work.

The Stanford team also developed the dendritic vaccine, which has shown efficacy in human trials for several years. There is currently no plan to bring the dendritic vaccine to market.

These two vaccines have already received far more testing than future bioterrorism vaccines will get before giving them to millions of healthy Americans. If the FDA can do that, they can give us our vaccines NOW.

With this new rule the FDA has revealed, for all to see, that they do not have to conduct lengthy, often unfair randomized trials while thousands die, that they CAN act swiftly when they want to.

A bioterrorist incident killing 2-3 thousand people is, of course, a possibility. But lymphoma killing over 24,000 people every year is a certainty. Are we willing to sacrifice thousands of lives waiting for these phase III results?

We have set up an online petition to demand that the FDA immediately approve lymphoma vaccines which have shown efficacy. To date, over 8,300 people have signed.

BioVest, a small biotech company, is manufacturing vaccine for the NCI randomized trial, using its patented Hollow Fiber process to grow cells for the required cells. It has been reported that this technology has considerably accelerated the vaccine production process, which once took months.

BioVest is working with the NCI under a CRADA (Cooperative Research And Development Agreement). The CRADA is a mechanism to transfer the vaccine technology—originally developed by NCI—to BioVest, after the trial is completed.

Our petition could be easily satisfied by approving the NCI/Levy vaccine under Accelerated Approval provisions.

Since these provisions often require a randomized trial, after approval, the ongoing NCI trial could satisfy the requirement. This is a simple way to make the vaccine available to patients, while satisfying the demands of science.

In our talks with BioVest's former CEO, he stated that the FDA requires a dedicated facility be built before the vaccine can be approved. The estimated cost is $20 million. It is unclear whether BioVest has actually requested the FDA to grant Accelerated Approval.

Recently, a company called Accentia has purchased an 81% interest in BioVest, for $20 million. We are hopeful that Accentia intends to build the dedicated facility ASAP. It is certainly evident, from the company's website, that Accentia has a strong interest in the NCI/Levy vaccine:

“The vaccine's powerful anti-tumor effect vastly exceeds that of non-targeted traditional therapy, as it arises from the immune system's defense cells' innate ability to selectively target foreign antigens. Most importantly, the immune response triggered by the vaccine against the cancerous tissue is a natural disease-fighting mechanism and has almost none of the side-effects associated with the broad-spectrum chemotherapy and radiation used to traditionally treat this type of lymphoma.”

Speaking of the 1997 Hsu trial of the vaccine, Accentia says:

“Analysis of the 32 first remission patients also shows an improved clinical outcome for those patients who mounted a specific immune response compared to those who did not (freedom from progression, 7.9 years v 1.3 years and a median survival from time of last chemotherapy that exceeded the time of observation v 7 years for non-responding patients).”

Accentia comments on the landmark 1999 (Bendandi) vaccine trial, done on patients in remission and with the immune stimulant GM-CSF added to the protocol:

“The final study results are even more striking, with 18 of 20 (90%) of the patients demonstrating continous clinical remission with a median followup of 42+ months. Tumor-specific cytotoxic CD8+ and CD4+ T cells were uniformly found (19 of 20 patients) in the patients treated. Vaccination was thus associated with prolonged clearance of lymphoma cells.

“These results contrast with the expected course of the disease after standard chemotherapy and radiation, which shows median relapse time for FL patients of three years, with 90% of patients dying of a tumor-related mortality within 7 years of the date of diagnosis.

Long-Term Followup and Study Results
Long-term follow-up of these patients in the Phase II was recently completed (summer 2003) and demonstrates in the study patients. Induction of CD4+ T cell response in 100% of patients, induction of CD8+ T cell response in 86% patients (defined by lysis of autologous lymphoma targets), induction of molecular remission in 75% of patients, and most critically, the median time to relapse has now exceeded 7 years since the start of the trials.”

This same vaccine is now embroiled in the above-mentioned randomized trial.

Some in the medical community feel that early approval of a new therapy could discourage patients' participation in randomized trials. However, we feel it is immoral to withhold an effective treatment from thousands of patients for such a reason.

We call upon BioVest and Accentia to enter into talks with the FDA to expedite the building of a dedicated facility to manufacture lymphoma vaccines, and to approve the vaccine under Accelerated Approval procedures.

Let us not forget: At the end of the day, the intended purpose of clinical trials—as well as the mission of the NCI and the FDA—is to save lives.

Lymphoma Vaccines Must Be Immediately Approved

Whereas the Food and Drug Administration (FDA) has amended its new drug and biological product regulations to allow marketing approval of new drug/biological products based on ANIMAL STUDIES ALONE when human efficacy studies are not ethical or feasible; and whereas use of the resultant new rule is LIMITED to expediting approval of products, such as vaccines, that may treat life-threatening conditions resulting from a possible terrorist attack;

And whereas a certain lymphoma vaccine has been shown in two phase II HUMAN trials to help significant percentages of patients achieve long remissions or possible cures of their disease—with minimal toxicity; and whereas that vaccine was not approved, but instead has been embroiled in randomized phase III human testing for over three years; and whereas certain other lymphoma vaccines, also currently in HUMAN trials, have shown efficacy;

And whereas under current FDA testing rules, all of these lymphoma vaccines will be unavailable to patients for more long years; and whereas there are NO FDA approved nontoxic therapies that can produce the same results without toxicity; and whereas, therefore, it is neither ethical nor feasible to conduct randomized trials of such vaccines; and whereas statistics have shown that thousands of lymphoma patients will die each year while testing of these lymphoma vaccines drags on; THE UNDERSIGNED HEREWITH DEMAND THAT ALL LYMPHOMA VACCINES THAT HAVE SHOWN EFFICACY BE IMMEDIATELY APPROVED BY THE FDA.

Sign the Petition
All who read this should Register their E-Mail address

An Open Letter to the FDA Commissioner

Dear Dr. McClellan: In your first statement as commissioner and your June 23rd speech before BIO, you said FDA will have to make changes to get new drugs to sick people sooner. We believe this should apply to effective older therapies also.

An effective Id-KLH lymphoma vaccine technique has been in trials since 1986, developed by Dr. Ron Levy and his associates at Stanford. In 1997 and 1999 definitive results were produced in phase II studies that simply cannot be ignored. The latter study produced 90% long remissions when vaccine was used following CR from chemotherapy. Side effects were minimal. Good results have also been achieved with a dendritic lymphoma vaccine, also developed by Levy and his colleagues.

Our group has circulated a petition to approve these vaccine techniques immediately; it has been signed by over 8300 people.

Unfortunately, approval of the dendritic vaccine is not being actively pursued, and the Id-KLH lymphoma vaccine has been bogged down for 3 years in a phase III trial sponsored by the NCI; the lead researcher is Dr. Larry Kwak. In September, Dr. Kwak declared on national TV (Nightline) that the trial may take at least five more years to complete. The reason? Poor patient accrual.

Poor accrual is not unexpected because patients in the trial are expected to take chemotherapy, including the cardiotoxic Adriamycin, when they may not receive the vaccine.

A company called BioVest has been making vaccine for the study under a CRADA with the National Cancer Institute (NCI). The hybridoma technology used for the Id-KLH vaccine was a time-consuming, therefore unprofitable procedure. However, BioVest has declared that using its “patented hollow-fiber technology” the procedure is greatly accelerated and the vaccine can now be manufactured at a profit.

Notably, Dr. Kwak has stated:

“It has been unequivocally established that Id vaccination of patients with follicular lymphoma administered when patients have minimal residual disease, has antitumor effect and potential to improve the clinical outcome.”

We want to know: Why cannot FDA work with BioVest to bring these processes to desperate patients, through Accelerated Approval, or other means?

In March of 2002, FDA enacted a new rule that allows vaccines and other remedies for bioterrorism to be approved based upon animal testing alone. The stated reason is the inherent difficulty in conducting a randomized trial of bioterrorism vaccines. We contend there is a similar difficulty in conducting a randomized trial of nontoxic lymphoma vaccines which deliver long remissions vs. toxic chemotherapy that does not.

We ask: If a bioterrorism vaccine that has not been tested in humans can be approved, why can't this safe vaccine be approved, since it has been tested in humans for 17 years?

The present drug-development system—rather than getting these successful treatments to patients expeditiously—has blocked their use for all these years and will block it for at least five more. This compels thousands of lymphoma patients to face multiple chemo treatments, highly risky bone-marrow transplants and death.

The system is clearly inappropriate for developing patient-specific therapies (PSTs) because only a small company can make a profit from PSTs while only a large company has the capital to develop them efficiently, under present rules. You yourself have stated it costs $800 million to bring one drug to market.

According to Dr. John Timmerman, who conducted the definitive dendritic lymphoma vaccine trial, “…clinical activity of DC-based vaccines has also been demonstrated in melanoma, prostate carcinoma, renal cell carcinoma, and carcinoembryonic antigen–expressing cancers.”

Therefore, the failure to provide a development path for cancer vaccines affects far more than just lymphoma patients.

If the development system is not changed, each and every technology for cancer vaccines and T-cell therapy will take many long years to get approved.

We urge the FDA to find a way to get these very promising therapies into the hands of doctors immediately—not only to save lives, but so they can start learning how best to use these technologies. This cannot be accomplished in the restrictive setting of a clinical trial. For example: Rituxan has been around since 1997. Yet only recently are trials being designed to find out if lymphoma vaccines will work following Rituxan administration.

It is, in fact, highly questionable whether techniques producing a different formulation for each patient should be regulated as drugs/biologicals at all. We urge the FDA to develop a separate, expedited development path designed for PSTs.

Bob Bennett
Cancer Drugs Now