The Food and Drug Administration has recently granted accelerated approval to the first treatment for a rare form of muscular dystrophy last month, after months of advocacy and speculation.

The FDA advisory committee and internal reviewers were not convinced that the drug worked, however the approval of the drug was fuelled by the emotional and passionate testimony of patients and their families. The approval has specified that the clinical benefit of the drug "has not been established" and is awaiting more results from follow-up clinical trials.

The process of the drug approval has been closely watched by patient advocates, parents and biotech investors and is expected to be an example to take the patients' point of view into account during the approval process. The approval came as a relief for many patients but what drew the skepticism of the reviewers was the extremely small sample size – merely a dozen boys.

Small sample size and short time frames

The 12 boys were selected from 13% of the 9,000 to 12,000 boys in the US carrying the gene mutation that causes Duchenne muscular dystrophy. The trial also did not show any improvement on walking tests, but it did show an increase in dystrophin in the body - a protein that is missing in the disease for some patients.

As such, many reviewers questioned if the increase of the protein would translate to a clinical benefit in long term use. The study also lacked a control group and was highlighted as a drug for management, not a cure.

Putting the decision and evidence together, it clearly reflects the power of patient lobbying, but it raises more important questions about the standards for drug approval by the FDA. This case raises a red flag for whether the FDA has a similar standard and process for many other drugs on the market - approved on a basis of preliminary data, smaller samples, shorter time frames, and sometimes lacking control groups.

An unusual move has indeed been recorded as the commissioner Robert Califf sided with Woodcock's decision to grant accelerated approval when he appealed his case.

"I find no basis for a view that Dr. Woodcock was unduly influenced by involvement with the patient community or other external pressures, and note that our understanding about how to include patients in the regulatory process is evolving," Califf wrote, in regard to the scientific dispute over whether the drug should be approved.

"In addition, serious shortcomings present in the eteplirsen development program should not be allowed to establish a broad precedent for therapeutic development in rare diseases."

Focusing on patient's perspective for accelerated approval

But his statement has no real effect as many worry that the approval of this drug could be a big regret in lieu of forthcoming drugs.

Diana Zuckerman, president of the National Center for Health Research, a nonprofit research organisation, said that a chilling effect would occur on those that are trying to develop treatments and cures.

"If this drug can be approved under those conditions, is there any drug that FDA won't approve? Why would a company spend all of its energy working to do the best possible research if they can get an approval based on a shorter-term study, less definitive data, as long as they encourage patient groups to advocate and lobby for them?" she asked rhetorically.

In a turn of events, the FDA has made patient perspective a factor to the drug approval process. There has been increasing movement as patients are more empowered today, compared to previous decades.

Richard Moscicki, deputy centre director for science operations at the FDA recalls an incident 20 years ago, "I said to FDA colleagues, "You really need to talk to a patient to understand what they're trying to tell you."

They said, "No, just the science. Don't want to be influenced or biased."

Now, it has been taken into account and Moscicki agrees that it has to be a careful procedure as the FDA is a science-based organisation that focuses on science, and should not approve drugs based on acclamation.

The priority review voucher, a cheat in the system

To add to the controversy, the company received a priority review voucher - given to all that has a qualifying drug approved - which in this case, it really is not. This canbe redeemed for a fast-track government review for one of its future drugs.

Alternatively, it can be sold to the highest bidder. Simply put, it can help a drug company leapfrog over a rival company.

"The only people who would buy a priority review voucher would be someone who had something that wouldn't merit its own priority review but they want the priority review," says Dr. Tim Coté, a former FDA official who now runs a consulting firm for rare disease drugs.

The terms of the voucher guarantees the company that their drug will be reviewed within six months instead of the normal ten months- but approval is not guaranteed, just a quicker decision. The voucher is also worth at least a few hundred million dollars.

Again, many skeptics including FDA officials and some academics have questioned whether the program is actually effective for the pharmaceutical industry and rare-disease advocates. What if the rival company's drug is better? What if the speedier decision meant the overlooking of some errors? What if reviewers need more time to address complex issues?

Dr. John Jenkins, director of the office of new drugs in the Centre of Drug Evaluation and Research at the FDA, has said that the voucher program is not the right incentive to promote drug development. FDA spokeswoman Sandy Walsh also mentioned that the "FDA has not seen evidence that the program is effective."

So maybe it is high time the FDA reviews its drug approval process for the sake of their reputation, the pharmaceutical industry and most importantly, the patients. MIMS

Read more:
Study claims many scientific publications from recent years are “unnecessary, misleading and conflicted”
Take artificial sweeteners with a big pinch of salt