What's Next for Alnylam Pharmaceuticals, Inc.?

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The past 15 years haven't been easy for Alnylam Pharmaceuticals, Inc. (NASDAQ: ALNY) shareholders. The company's new drug candidates are based on science that earned a Nobel Prize in 2006, but proving a clear clinical benefit that outweighs any safety concerns hasn't been nearly as easy. 

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This pioneering biotech took a big step forward recently with its first late-stage clinical trial victory, easing some valid concerns in the process. There are plenty of maladies caused by troublesome genes, and Alnylam has had plenty of early success targeting a handful. With surprisingly good data for its lead candidate in hand and a stable of potential new drugs in earlier development stages, we can expect a flurry of activity in the years ahead. Here are a few key developments to look for.

Safer than expected

Alnylam scored its first late-stage clinical trial victory in dramatic fashion. Nearly a year ago, a patient death forced the company to cease development of revusiran, a drug that works in a similar manner as patisiran to treat hereditary transthyretin-mediated amyloidosis. Patisiran is intended to reduce nerve damage, while revusiran was supposed to reduce heart damage, but both do so by limiting expression of faulty transthyretin genes. Transthyretin is an important transport protein, and investors were concerned that limiting its production might cause more problems than it solves.

The recently announced Apollo trial results should melt those concerns away. Patisiran smashed through the efficacy goals set before it and did so with a stellar safety profile. Investigators reported higher rates of side effects, dropouts, and patient deaths in the placebo group than in the group of patients receiving patisiran. 

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Hereditary transthyretin-mediated amyloidosis (ATTR) is a chronic, debilitating, and often fatal illness that affects about 50,000 people worldwide. These patients lack effective treatment options, which is why the Food and Drug Administration agreed to give a patisiran a priority review years ago. The company intends to file an application with the FDA before the end of the year, which could lead to an approval and commercial launch as early as next summer.

Predicting peak sales potential for patisiran isn't easy. Among the world's ATTR patients, perhaps 10,000 suffer peripheral nerve damage that patisiran is intended to treat, and revusiran was aimed at the other 40,000 that suffer heart damage. Of course, plenty of ATTR patients suffer from both symptoms. This is why peak annual sales estimates for patisiran range from $200 million, to over $750 million.

We should have a clearer picture of patisiran's potential among the larger group of ATTR patients that predominately suffer from heart damage soon. In early November, Alnylam will present full Apollo trial results at a scientific conference, including an exploratory analysis of a subgroup with cardiac involvement.

Tomorrow's lead programs

Although patisiran's upcoming new drug application will be the first in Alnylam's 15-year history, the next two might not be much further ahead. Earlier this month, the company "reached alignment" with the FDA concerning a path forward for acute hepatic porphyria candidate, givosiran.

The agency will allow the company to use reduction of a biomarker associated with disease activity to prove givosiran's efficacy at an interim analysis three months after beginning treatment. That's a huge win because the alternative would involve following these patients around for years to measure actual outcomes such as hospitalization rates. Givosiran reduced the biomarker by 80% in a previous study, which means there's a good chance the company could be ready to file givosiran applications in late 2018. 

Givosiran addresses a population of patients too small to warrant blockbuster expectations, but fitusiran for hemophilia could cross the $1 billion annual sales threshold. Global spending on medicines to treat the rare bleeding disorder are expected to top $10 billion this year, but a growing number of patients have developed inhibitors to presently popular clotting factor replacement therapies. In a previous study, the median annualized bleed rate for a group of 14 hemophilia patients with inhibitors plunged from 38 to zero following fitusiran treatment.

Based on the strength of early trial results, Alnylam began three late-stage studies which it recently had put on hold due to a patient death. Based on the events leading up to the patient's demise, though, it doesn't look like fitusiran was responsible.

Alnylam and the FDA will need to agree on a risk-mitigation strategy before recently initiated late-stage studies can continue. Investors will want to keep a close eye on this program. If it can restart and finish without further catastrophe, fitusiran could be the most valuable candidate in the company's pipeline right now.

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Cory Renauer has no position in any of the stocks mentioned. The Motley Fool owns shares of and recommends Alnylam Pharmaceuticals. The Motley Fool has a disclosure policy.