Alnylam hits all key endpoints in crucial trial of rare disease drug


T

he age of RNA interference drugs has arrived.

Alnylam Pharmaceuticals announced positive results Wednesday from a closely watched phase 3 clinical trial of patisiran, the company’s lead drug designed to treat a rare nerve disorder known as familial amyloid polyneuropathy (FAP.)

Most importantly, the safety profile of patisiran in the FAP study looks clean, assuaging concerns raised by toxicity reported with some of Alnylam’s other pipeline drugs.

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Based on these positive results, Alnylam and its partner Sanofi intend to seek U.S. marketing approval for patisiran before the end of the year. A European approval filing will follow in early 2018.

Patisiran, if approved, would also become the first commercial product based on RNA interference, or RNAi, a technology that uses snippets of genetic code to shut down disease-causing genes. The scientists who invented RNAi were awarded the Nobel Prize for Medicine in 2006. Many years and more than $1 billion in research later, Alnylam is finally on the cusp of proving that RNAi can be transformed into a medicine that helps patients.

Alnylam shares rose 22 percent to $91.83 in early Wednesday trading. The stock value of Ionis Pharmaceuticals, developers of a competing antisense drug for FAP, fell 9 percent.

In the study of 225 FAP patients, which Alnylam calls APOLLO, patisiran significantly reduced a measure of nerve damage compared to placebo, achieving the primary endpoint with statistical significance. All secondary efficacy endpoints were also met, the company said.

The frequency of serious adverse events were comparable across both arms of the study and the death rate was lower for patisiran-treated patients, Alnylam said.

Detailed data from the study were not disclosed so they can be presented at a later medical meeting.

“We are very proud to report the first ever positive Phase 3 results for an RNAi therapeutic, marking the potential arrival of an entirely new class of medicines. This moment is the culmination of a 15-year journey of tireless work by countless contributors who have overcome enormous scientific and business challenges to make RNAi therapeutics a reality,” said John Maraganore, Alnylam’s CEO, in a statement.

Familial amyloid neuropathy is caused by a mutation in a gene that leads to the accumulation of damaging TTR protein in nerves and other tissues. Worldwide prevalence is estimated to be approximately 10,000 patients.

Patisiran, delivered via an infusion, is designed to turn off the disease-causing gene and knock down the levels of TTR protein.

With this morning’s spike in Alnylam’s stock price, the company is worth a rich $10 billion. Current analyst forecasts have patisiran generating more than $1 billion in peak sales, which means Alnylam is still under pressure to replicate the drug’s success with other RNAi drug projects in its pipeline.

Last fall, development of the drug candidate revusiran was discontinued due to an imbalance in cardiovascular deaths in a phase 3 clinical trial. Earlier this month, Alnylam temporarily suspended clinical trials of the hemophilia-targeted drug fitusiran due to the death of a patient from a blood clot.

Alnylam continues to develop givosiran, targeting a rare liver disease, which is moving into a phase 3 clinical trial later this year with an interim analysis reading out in the middle of 2018. Inclisiran, which Alnylam is developing in partnership with The Medicines Co., is a cholesterol-lowering therapy targeting the crowded and reimbursement-challenged PCSK9 market but with convenient, twice-per-year dosing.

Still in early-stage clinical trials but increasingly important is Alnylam’s ALN-TTRsc02, another potential blockbuster targeting a different form of TTR depositing disease.



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