- Alnylam Pharmaceuticals, Inc. said Wednesday a Phase 3 study testing its experimental therapeutic patisiran met all of its primary and secondary objectives in a rare and debilitating genetic disease, a major step forward to validating the Cambridge biotech's RNA interference drug platform.
- Alnylam plans to file patisiran for U.S. approval as a treatment of hereditary ATTR amyloidosis patients with polyneuropathy later this year, with an application to the European Medicines Agency slated for early 2018.
- Patisiran's success should largely silence lingering doubts about Alnylam's approach that emerged in the wake of a clinical setback last fall for the company's then lead candidate. Shares in Alnylam rose nearly 40% in morning trading Wednesday, a jump that pushes the company's valuation near $10 billion if sustained.
Success in the study, dubbed APOLLO, puts Alnylam in position to win the first regulatory approval of a drug based on RNA interference.
"These data exceed all of our hopes and expectations," company CEO John Maraganore said on a call with investors Wednesday morning.
With RNA interference, Alnylam aims to target and "silence" the messenger RNA responsible for the production of disease-causing proteins. In hereditary ATTR (hATTR) amyloidosis, mutations in the TTR gene cause amyloid deposits to build in organs and tissue, leading to progressively debilitating neuropathy.
The disease usually manifests itself as either polyneuropathy due to deposits in nerves or as cardiomyopathy due to deposits in the heart. It is a progressive condition that can lead to death and no treatments are currently approved in the U.S.
Patisiran is designed to block creation of the TTR protein in order to clear those problematic deposits in peripheral nerves and heart.
In the study, treatment with patisiran reduced the progression of neuropathy and improved patient quality of life — in addition to hitting a clean sweep of five additional secondary endpoints.
Just as importantly, the drug's safety profile looked clean, with lower rates of serious adverse events and deaths for patients treated with patisiran compared to those on placebo. Roughly 7% of patients in the active arm of the study discontinued treatment, versus more than a third of patients in the comparator cohort.
No deaths were judged to be directly tied to patisiran.
Safety issues have been a concern for Alynylam investors ever since patient deaths in a study of the company's now-discontinued revusiran program led the company to halt further development of that drug last fall.
Revusiran was also designed to treat hATTR amyloidosis patients, but for those specifically with cardiomyopathies. A company-led investigation into the patient deaths turned up no clear answers on cause, yet the safety signal led to concerns about both Alnylam's delivery vehicle as well as its RNAi platform.
Patisiran's performance potentially mitigates those concerns and puts the company on track to evolve into a commercial-stage company.
Alnylam only presented topline results on Wednesday, noting statistically significant reductions on the study's primary measures but leaving detailed results to be presented at an upcoming medical meeting in November.
If patisiran is approved by the Food and Drug administration, company executives expect to launch the drug by mid-2018, targeting the 20,000 to 30,000 hATTR amyloidosis patients with polyneuropathy.
The company is partnered with Sanofi SA, which over three years ago bought a 12% stake in Alnylam for $700 million. Sanofi will take the lead in securing future approvals for the drug in markets outside the U.S. and Western Europe, such as Japan and Brazil.
Patisiran's success may also serve to boost confidence in the rest of Alnylam's RNAi pipeline.
In addition to patisiran, Alnylam is moving givosiran into a Phase 3 study for acute hepatic porphyrias and the company still has high hopes for its hemophilia candidate fitusiran, despite recent safety worries there as well. A partnership with The Medicines Company on the PCSK9 synthesis inhibitor inclisiran adds yet another potential catalyst.