Alnylam RNAi drug reverses progress of rare fatal disease: study

(Reuters) - More than half of patients with a rare, rapidly progressing often fatal genetic disorder experienced significant improvement after being treated with an Alnylam Pharmaceutical Inc drug that uses gene silencing technology, according to results of a late stage study presented on Thursday.

Alnylam shares rose more than 17 percent, to $142.16. Ionis Pharmaceuticals Inc also presented data for a rival drug that while positive appeared to pale in comparison to the Alnylam results, and its shares fell more than 9 percent to $52.39.

The Alnylam drug, patisiran, was being tested against hereditary ATTR (hATTR) amyloidosis with polyneuropathy, which affects an estimated 50,000 people worldwide. It is being developed in partnership with Sanofi.

When Alnylam announced in September that the trial succeeded, its shares surged 51 percent.

If approved, patisiran is forecast to reach annual sales of $1 billion by 2023, according to Thomson Reuters data.

More than 90 percent of those who received patisiran infusion every three weeks in the 225-patient trial experienced a halt in disease progression, and 56 percent showed an improvement in their condition after 18 months, the companies said.

“Patients with hATTR amyloidosis ... have a profound need for effective and safe treatment options,” Dr. David Adams, the study’s lead investigator, said in a statement. “As a clinician, it has been deeply rewarding to see the potential impact patisiran may have on the lives of hATTR patients.”

On a neurological disease impairment scale, patisiran patients’ scores on average declined by 6 points, indicating improvement, while scores of those who received a placebo worsened by 28 points, data presented at a medical meeting in Paris showed.

The mean 34-point difference was deemed highly statistically significant.

In addition, 51 percent of patisiran patients reported improvement on a quality of life scale, with a mean 6.7-point improvement at 18 months versus a 14.4-point worsening for placebo recipients, a 21.1-point difference.

In the study of the Ionis drug, inotersen, the mean difference versus placebo on neurological impairment was 19.7 points, and for quality of life 11.7 points, both after 15 months.

Leerink Partners analyst Paul Matteis said patisiran safety data also looked superior to the Ionis drug. “We think the Alnylam data are confirming to the current consensus view that patisiran will be the market leader.”

Patisiran belongs to a new class of medicines that employ RNA interference, or RNAi, which prevents a defective gene from making disease-causing proteins.

If unchecked, the gene mutation causes amyloid proteins to accumulate in peripheral tissues of the nerves, gut and heart, causing damage to organs and tissue and a wide range of debilitating symptoms. Patients have a life expectancy of 2.5 to 15 years from symptom onset.

The companies plan to file for U.S. approval by year end and in Europe shortly after. It would be Alnylam’s first approved medicine and validation for the long-held promise of RNAi technology.

The most common patisiran side effects were peripheral edema and infusion-related reaction that led to one patient discontinuation. Of serious adverse side effects reported, only a case of diarrhea was deemed related to patisiran.

Reporting by Bill Berkrot; Editing by Dan Grebler and Tom Brown