Earlier this week a congressional report released by the GAO stated the FDA was lax in their follow-up on drugs granted accelerated approval. Further, the FDA had never pulled a drug off the market for non-compliance of required follow-on efficacy data.
Not to trivialize a complicated topic, but the reasons are simply that these drugs are 1) safe and 2) life saving.
In fact, the accelerated approval process is arguably the best thing to happen to drug development. Since it’s enactment in 1992 it has saved hundreds of millions in development costs while making safe drugs available to patients several years earlier than normal.
Most drugs granted accelerated approval are for the treatment of cancer. As we all know, there is no one single therapy for many forms of cancer. Cancer is treated with combination therapies and no one single combination is equally effective in all patients. Treatment options are not standardized and often evolve depending how a patient is responding. So, while the efficacy of a single drug or treatment regimen may vary, all drugs have relative safety in common. The point being that if a drug is safe and available oncologists will use it. Cancer patients rely on hope and the more treatment options available the better.
The safety of a drug is determined in Phase I clinical trials where the maximum tolerated dose and resulting toxicities are determined. Phase II trials establish the effective dose and depending on trial design one may see efficacy. Phase III trials establish superiority over existing therapies and generally involve large numbers of patients and significant costs. The combined time to conduct Phases II and III can be five years or longer. The accelerated approval process can reduce this time by more than half and may eliminate the most costly trial in the drug development process, Phase III.
Accelerated approval regulations allow for clinical trials to rely on a “surrogate endpoint that is reasonably likely…to predict clinical benefit…”. An example would be tumor shrinkage. The sponsor, working through the FDA’s special protocol assessment procedure, gains agreement from the FDA on trial design and the surrogate endpoint and that the trial, if positive, can support approval. Subsequent to approval the sponsor is required to confirm clinical benefit through post-marketing studies.
Since 1992, 64 drugs (27 cancer, 22 HIV) have been approved under accelerated approval regulations for 90 indications and not one has been removed from the market. That pretty much sums it up. The process works and ought to form the primary basis for oncology drug development. Not only would patients benefit from more options, but ultimately as development costs are reduced the prices for these expensive drugs will fall.