A Proposed New FDA Drug Approval Pathway: “Conditional”

Al Musella DPMMarty Tenenbaum PhD

Al Musella, DPM, President, Musella Foundation For Brain Tumor Research & Information, Inc., Hewlett, NY

Marty Tenenbaum, PhD, Founder and Chair, Cancer Commons, Los Altos, CA

Q: The delay time from discovery/observation, through validation to approval and distribution/use of new cancer treatments remains excessive. With promising experimental treatments, advanced computer technology and biostatistics, creative alternatives to traditional randomized clinical trials, and a government seeking efficiencies, might it now be time for the FDA to issue: “Conditional Approvals”?

A: The first advances in oncology occurred at a time when there were no regulations. Doctors had ideas, and put them to work immediately. They adjusted and combined treatments as needed until they were optimized and became standard treatments. Many types of cancer were cured by this work.

Unfortunately, for patients, with glioblastoma, pancreatic cancer and other rarer cancers, the prognosis remains dire: average survival with currently approved treatments is less than 2 years. These patients can’t afford to wait a decade or more for new drugs to be approved.

The good news is that the oncology drug development pipeline is full of promising targeted- and immuno-therapies that have already demonstrated safety and at least some evidence of effectiveness. However, under current regulations, it will take years before the average patient can get access to these potentially life-saving treatments. Moreover, it is likely that a cure will involve intelligent combinations of treatments. Under current regulations, combination testing cannot even begin until these drugs are approved. And what if a new treatment was not effective as a monotherapy, but could be an essential component of a multi-drug cocktail, say to block a resistance pathway. Catch 22. Under current regulations, many good ideas will never get to patients, and those that do get approved have to be priced so high that many patients cannot afford them.

We would like to propose a new pathway to FDA approval – the “Conditional Approval” – that addresses these issues. It would allow the FDA to approve a treatment that shows safety and a biological effect in a small group of patients. (Click HERE for more details). The twist is that it would require patients using these drugs to participate in a registry where their doctors submit details on the treatments they use, side effects and outcomes.

Conditional approval would be granted to treatments that have been proven safe in a clinical trial(s) with at least 25 patients, and have demonstrated biologic activity: an improvement in a biomarker, brain scan, progression free survival or overall survival.

Once approved, the treatment could be offered as if it had a standard approval, and could not be denied by insurance as being “experimental”. However, all patients who use a conditional treatment would be required to participate in a registry for the duration of the conditional approval period, and to sign a consent form acknowledging and agreeing to the risks inherent in undergoing a treatment whose safety and efficacy have not been fully tested.

The FDA would conduct periodic reviews of this registry data, with three possible determinations: 1) If the safety is questionable or if the results look worse than the standard treatments, conditional approval would be withdrawn, and the manufacturer could continue on the standard paths of approval. However, the FDA could not use these results against the standard approval tracks, as the patient population was not controlled and patients were combining other treatments with it; 2) If the results look at least 20% better than the standard treatments, in the first 50 patients over a predetermined period of time, full approval is granted; or 3) If the results are similar to standard treatments, the conditional approval is maintained until the review shows either the treatment is good enough for full approval or bad enough to withdraw approval.

The decision to try a conditionally approved drug, alone or in combination, would be up to treating physicians, who could consult with peers through a network linked to the registry or use a decision support app that exploits the registry as a database (e.g., show me all treatments and combinations that have been tried on similar patients, sorted by most effective, most cost effective, best risk / benefit ratio, cost, or least side effects.) Such apps could also support low cost point-of-care ‘registry trials,’ whereby patients are dynamically assigned to treatment arms based on expert recommendations and clinical outcomes for similar patients.

It is painfully obvious that the way to cure our currently incurable cancers is to use a combinational approach. We may well have the necessary tools available today—but we are not allowed to use them. When faced with certain death, we believe it is acceptable to not have 100% proven safety and efficacy. We will be approaching the FDA with a request to pilot conditional approval in brain cancer – because life and death decisions should not be made based on regulations – they should be based on what is best for the patient, as determined by the patient and his/her doctors.

We have been working on this plan for a while, but we think now is the time for it to actually be approved. Everything is coming together – like the perfect storm:

  1. We finally have a few experimental treatments in the pipeline that look really good.
  2. The new President is slashing regulations and calling for faster FDA approvals and for slashing drug prices.
  3. Computer technology and biostatistics have reached the point where our plan for a registry trial can be just as reliable as traditional phase 3 trials – maybe more so.

IF this proposal is put into effect, it could lead to rapid advances in the treatment of brain tumors, and the possibility of a breakthrough cure in a few years, instead of the decades it would take on the current path.

We need your support, and will be reaching out in a few weeks for help with writing letters and making phone calls. Meanwhile, we welcome your thoughts.

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