The United States Food and Drug Administration (FDA) approved the drug eteplirsen on a limited applicative basis last month, for sufferers of Duchenne Muscular Dystrophy (DMD), in a controversial move contested right up to the point of approval.

Estimated to affect one in 3,500 live births in Singapore, this brings renewed hope for those who suffer from the debilitating disease.

Accelerated approval due to “serious unmet need”

The approval with caveat was granted under a special scheme that is reserved for drugs are potential treatments for serious diseases with an unmet medical need. This was a special situation that warranted special approval, and that this approval of will not lower the standards for general drug approval, the FDA said in a media release.

“In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease and the lack of medical understanding of many disorders,” said Dr. Janet Woodcock, FDA Medicine Review Division Head, in the statement that granted this approval.

This drug was approved specifically for patients who has a confirmed mutation of the dystrophin gene amenable to exon 51 skipping, and constitutes to approximately 13% of those living with DMD.

The caveat from the FDA is that the drugmakers must conduct a randomised controlled clinical lasting two years to verify the efficacy of the drug. The trial is considered to be successful should it be able to aid in the improvement of motor functions. Should the results of the trial be unsatisfactory, the FDA would have the jurisdiction to suspend this approval.

Overturned previous FDA decision

In making this decision, the FDA overruled its advisory panel, who in April this year raised questions regarding the effectiveness of the drug due to the extremely small clinical trial size of 12, and the viability of the six-minute walking test that trial participants underwent. The panel voted by a narrow margin to deny the approval of the drug and agreed that the drug was not effective.

The point of contention was the question of the drug being able to sufficiently produce higher levels of dystrophin– a protein that prevents muscle fibres from degenerating and rendering impossible voluntary movement.

Despite the presence of conflicting and debatable evidence, Janet Woodcock emphasised that the failure to approve a drug that actually works in devastating diseases can result in extreme consequences.

This approval was successful in part due to lobbying by parents of children suffering from DMD – reminiscent of the movement three decades ago to force regulators into approving AIDS treatments.

Sufferers of DMD – mainly males – would first notice symptoms in their infancy, characterised by the delay of motor milestones, including sitting and standing independently. Males who are diagnosed with DMD would typically start walking at 18 months. From ages six to 11, they would experience a gradual loss of muscle strength, and by age 12, are usually confined to a wheelchair.

Individuals with DMD rarely live past 30 years of age as a result of complications, ranging from breathing difficulties, enlargement of the heart, and in some rare cases, stunning of intellectual growth. Although patients have greeted the news with eager relief, the treatment is estimated to cost USD 300,000 (S$ 408,000) per annum. MIMS

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Sources:
http://www.cfps.org.sg/publications/the-singapore-family-physician/article/93
http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2016/206488Orig1s000ltr.pdf
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm521263.htm
http://www.raps.org/Regulatory-Focus/News/2016/09/19/25870/Sarepta-Wins-Controversial-FDA-Approval-for-First-DMD-Drug/#sthash.d09I7qkr.dpuf
https://www.statnews.com/pharmalot/2016/09/19/sarepta-wins-dmd-drug-approval/
http://www.scientificamerican.com/article/fda-approves-first-drug-for-duchenne-muscular-dystrophy/
http://www.marketwatch.com/story/sareptas-controversial-duchenne-muscular-dystrophy-drug-was-contested-right-up-to-approval-2016-09-19
https://www.genome.gov/19518854/learning-about-duchenne-muscular-dystrophy/