Alnylam Advances RNAi Drug Results After Two Years of Treatment

Xconomy Boston — 

Alnylam Pharmaceuticals is marching forward in its pursuit of developing a pair of RNA interference drugs that aim to reduce the levels of a protein known to cause a type of rare disease that can harm the nervous system or the heart—but there’s still plenty of work left to be done, even after the company released updated data today from a Phase 2 extension trial.

The results from the study showed some improvement for Alnylam’s most advanced candidate, patisiran. Alnylam (NASDAQ: ALNY) reports that patisiran, which must be infused at a hospital, improved the neurological function of most of a small group of 27 patients who took the drug for 24 months, even more than it did after 12 months.

The Phase 2 extension trial was studying patients who have a classification of the disease, familial amyloidotic polyneuropathy (FAP), that’s associated with severe pain or loss of autonomic nervous system function. The extension study measured results using a standardized score against historical data—data based on other Phase 3 trials and scientific literature. It is not a randomized trial or a comparison to placebo, which Alnylam is doing in a separate Phase 3 trial.

The results for Alnylam’s other candidate, revusiran, showed less luster. Revusiran was being studied in a similar Phase 2 trial against historical data, but on a version of the disease that can cause heart failure, or familial amyloidotic cardiomyopathy. Studying how far patients walked for six minutes before being injected with revusiran and after, Alnylam characterized the results as “in line” with historical measures of other drugs.

Patisiran is more advanced, but revusiran has drawn attention because it is a subcutaneous injection. Patisiran has to be infused at a hospital, a more arduous task for patients. There was also interest in the revusiran results because it was the first longer-term study of the drug’s use.

Shares of Alnylam’s stock did rise after the results by almost 9 percent to $60.47 by 1:05 p.m. today in New York. That may have been related to a hint of positive news from the Cambridge, MA-based company: It expects to complete enrollment for a Phase 3 trial of revusiran this summer, which may mean results could be available by 2018.

In the patisiran study, patients were measured by what’s known as the “modified neuropathy impairment score.” A decrease in the score—which measures things like muscle weakness, reflexes, and how patients respond to heat or touch—means patients are improving (and a higher score means they are suffering more nerve damage). The 24 patients on patisiran for 24 months had a 6.7 point decrease. For the 20 patients on patisiran for 12 months, it was a 2.5-point decrease on their scores, on average. In the historical results that Alnylam compared this study to, patients saw an increase of 26 to 30 points at 24 months, the company says.

Measuring the drug’s ability to improve neurological function—a factor in how the drug makes the patient feel—is still noteworthy because it may be seen as validation of the scientific hypothesis behind RNAi drugs. Xconomy dove deep into the details of patisiran’s Phase 2 results and how they are measured in April 2015.

The RNAi drugs target transthyretin, or TTR, a protein that’s produced in the liver. If there are mutations in the protein, it can build up and cause damage to nerves, heart, and other organs. About 10,000 people suffer from the nervous system-related version of the disease, and about 40,000 worldwide are affected by the cardiac type, Alnylam says.

As Xconomy previously reported, the only treatment options for FAP patients are a liver transplant, or Pfizer’s tafamidis (Vyndaqel), which is approved in Europe but not in the U.S. Alnylam is also in a race with another maker of RNA-based drugs, Isis Pharmaceuticals (NASDAQ: ISIS), which is co-developing a treatment with GlaxoSmithKline called ISIS-TTRrx that’s also in late-stage testing.