PTC Therapeutics (NASDAQ:PTCT) jumped last week on news that a key EU regulatory committee recommended conditional approval of Translarna, a treatment for Duchenne Muscular Dystrophy (DMD).
DMD is an ultrarare disease that affects muscle development in young boys. There a few treatments approved for the condition and, sadly, most patients diagnosed with DMD are wheelchair bound by 12 years old and pass away in their 20s. Since the need for new therapies is great, let's take a closer look at Translarna and the impact it may have for patients and PTC investors.
First, a bit of background
DMD is caused by gene mutations that affect the production of dystrophin, a key protein necessary for muscle function. Most children are diagnosed with DMD by the time they are six years old and few patients live beyond 25 years.
There are four main types of DMD gene mutation that interfere with dystrophin production:
- Deletions -- where a part of the gene is deleted
- Insertions -- where the gene has an additional piece of DNA
- Duplications -- where a repetition of a part of the gene exists
- Point mutations (nonsense mutation) -- where a missing piece of the gene halts dystrophin creation
PTC's Translarna treats only the fourth type of gene mutation and Translarna (if approved) is likely to only be used at first to treat those at least five years old that can still walk. That means Translarna would be an appropriate therapy in just 10% to 15% of all DMD cases. Since DMD is in itself rare, occurring in just 1 of every 3,000 male births, PTC estimates the patient population for Translarna is just 2,000 boys in the U.S. and 2,500 boys in the European Union.
One competitor stumbles, another advances
In the past, drug makers have had little success in creating effective DMD therapies, but three companies have reported results for new DMD drugs in the past year, albeit with mixed results.
Last fall, Prosensa's (UNKNOWN:RNA.DL) promising DMD drug drisapersen failed in late stage trials after posting solid results in smaller, earlier trials. Prosensa's partner GlaxoSmithKline studied drisapersen in 186 boys during the failed phase 3 study; however, patients receiving the drug did no better than patients receiving placebo in a six-minute walking distance test. Patients receiving drisapersen also failed to show significant improvement versus placebo in secondary endpoints of motor function in a 10-meter walk test, four-stair climb, and in the North Star ambulatory assessment, which is used in ambulatory boys and offers a moderate to good correlation to the six-minute walking test.
That phase 3 failure was particularly disheartening because prior results in phase 1/2 trials were solid enough for the FDA to grant breakthrough status for the drug, although Prosensa recently announced a new regulatory path for approval, so perhaps the drug can get back on track.
Prosensa isn't the only company to see its DMD drug face hurdles in the past year. Sarepta Therapeutics' (NASDAQ:SRPT) eteplirsen has endured a similarly rocky road.
During a small study last year, Sarepta reported eteplirsen helped kick start dystrophin production in DMD patients by skipping exon 51 of the dystrophin building gene; however, the FDA initially balked at providing a pathway for early approval because of worries over the trial including just 12 patients. That news sent Sarepta's shares reeling last fall, knocking them down 77% from their peak.
In the wake of push-back from DMD patients, the FDA has since shifted course and now appears willing to consider conditional approval of eteplirsen if Sarepta conducts additional studies that confirm the drug's efficacy and safety as demonstrated in its previous trial.
During that earlier trial, patients saw their six-minute walk test performance improve by nearly 65 meters versus placebo at week 120. If Sarepta can build on that performance this year, the company could have enough data to submit an application to the FDA for conditional approval by year end.
If so, Sarepta and Prosensa could be filing in the relatively near future, maybe a little behind PTC Therapeutics, which appears to have found a similarly willing audience for Translarna in EU regulators. PTC is moving Translarna into a confirmatory phase 3 trial this year and EU regulators could give PTC a conditional marketing approval for Translarna in the EU this year.
Fool-worthy final thoughts
DMD is a challenging disease with a high unmet need. It remains to be seen whether PTC, Prosensa, or Sarepta can garner approval, but if they can their drugs will mark the first significant advance in treating DMD, offering new hope to thousands of young boys.