Blog : Sarepta’s DMD strategy – develop 20 similar drugs

Tuesday, November 27, 2012

Finding a treatment for Duchenne muscular dystrophy (DMD) wont just mean developing one drug, says Chris Garabedian, president and CEO of Sarepta Therapeutics (Nasdaq:SRPT). It will mean developing as many as 20.

The fatal inherited disorder affects one in 3,500 young boys, confining most of them to wheelchairs by the age of 12. Few patients with it live past the age of 30. Years of telethons by the Muscular Dystrophy Association and comedian Jerry Lewis have raised awareness of the disease, but today, available treatments are mostly limited to steroids - which only prolong the boys ability to walk by 2-5 years - and surgery, including heart transplants, according to the National Human Genome Institute.

After Sareptas announcement this week that it will begin development of a fourth drug candidate for the treatment of DMD, Garabedian told Mass High Tech that the company is close to understanding the very origins of the disease in mutations of one of the longest genes in the human body, which is responsible for creating the muscle protein, dystrophin. Seraptas approach is to develop drugs which skip certain sections of the DNA where mutations inhibit production of dystrophin. While that wouldnt cure the patient, it would turn the disease into a much milder and more easily-manageable form, said Garabedian.

The Cambridge biotech released promising data from a Phase 2b study of its lead candidate, eteplirsen, in October, showing that after 48 weeks, boys with that particular gene mutation were able to walk further, and their bodies produced more muscle protein. That data has resulted in a doubling of the companys stock value in the past two months to $30.60 as of Tuesday.

But while eteplirsen aims to skip exon 51 of the DNA, that particular mutation is only present in about 13 percent of patients, according to the company. The next most-common mutations, which occur in exons 45 and 53, are present in about 6 percent of patients, said Garabedian. Different drugs would be required to treat each particular mutation of the disease.

Garabedian said that Sareptas technology platform allows it to make small changes to address each type of mutation. The company is currently prioritizing the top five, which are responsible for about half of all cases.

Theyre all essentially the same drug, he said. The only thing thats different is we have a different sequence of these subunits.

But gaining approval for so many drugs - Garabedian said it could eventually be as many as 20 - under the current standards of the U.S. Food and Drug Administration would be prohibitively expensive due to the difficulty of finding patients that have each of the mutations believed to cause the already-rare disease. As a result, the companys strategy has been to convince the FDA to approve an entire class, or platform, of drugs, said Garabedian. That would allow us to manufacture and sell all the other 20 of the drugs, he said.

The idea has been applied, according to Garabedian, to drugs such as influenza vaccines, in which the exact formulation isnt constant from year to year, based on different strains. However, he said, approval for a class of drugs represents a big change in the agency when it comes to increasingly complex, gene-based drugs which now hold promise for some of the most elusive and rare diseases.

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Blog : Sarepta’s DMD strategy - develop 20 similar drugs