Alnylam Shares Boom on Early Data For Subcutaneous RNA Drug

Xconomy Boston — 

Shortly before kicking off its R&D day, Alnylam Pharmaceuticals (NASDAQ: ALNY) got a boost from investors this morning that were thrilled that it just might be able to deliver RNA-based drugs with an injection right under the skin.

Cambridge, MA-based Alnylam released results from an early-stage clinical trial of ALN-TTRsc, a subcutaneous form of the drug it is using to treat patients with the rare disease known as transthyretin (TTR) amyloidosis. In a study of 40 healthy volunteers in the U.K, Alnylam reported that ALN-TTRsc reduced the level of patients’ TTR, the disease-causing protein that builds up in the tissue of the body as a result of the condition, by more than 80 percent—consistent with what it saw in pre-clinical studies. Alnylam also said the drug has been “generally safe and well tolerated” by subjects in the trial and that the results were statistically significant, meaning they weren’t due to chance. Alnylam’s shares surged about 13 percent in early trading and sat at about $42.61 apiece as of 9:45 am ET—they were worth $12 apiece roughly a year ago.

Alnylam noted that the study is ongoing, and that it will release the full results from the trial at a scientific meeting in September. It plans to start a mid-stage clinical trial later this year, and, assuming good news from that study, is eyeing a pivotal trial—the last needed before regulatory approval—at some point in 2014.

The reason for the optimism surrounding the data is that Alnylam has taken a small step towards showing that it can deliver RNA drugs through a more convenient subcutaneous injection, rather than via an intravenous infusion. Should Alnylam prove this delivery method can work, its plan is to apply it to the rest of the drugs in its pipeline. Alnylam CEO John Maraganore, for example, said in a statement that delivering drugs this way “has become [Alnylam’s] primary approach” to developing its RNA-based therapeutics.

“[The study] confirms human translation of [this] approach,” Akshay Vaishnaw, Alnylam’s executive vice president and chief medical officer told investors and analysts at its R&D day. “It shows that we have subcutaneous delivery with a very wide therapeutic index available to us now. We plan to use this on all of our pipeline programs.”

Alnylam plans to have five drugs in clinical trials by 2015, and is also developing an RNA-based drug for hemophilia, among other disease types.

TTR amyloidosis is an inherited condition in which excessive amounts of amyloid proteins build up in tissues of the body, leading to progressive damage to the heart and nerves, and ultimately death. About 10,000 people in the world have the nerve-damaging form of TTR amyloidosis (called familial amyloidotic polyneuropathy, or FAP), while an estimated 40,000 worldwide have the form that affects the heart (named familial amyloidotic cardiomyopathy, or FAC), according to Alnylam.

People who develop symptoms of FAP—typically those between 40 and 60 years old—tend to live for another five to 15 years after their symptoms appear. Those diagnosed with FAC typically live about 2.5 more years, Alnylam says.

The only options for people with the FAP are a liver transplant or Pfizer’s tafamidis (Vyndaqel), which is approved in Europe but was rejected by the FDA in July 2012. There are no approved therapies for patients with FAC. Alnylam’s mid-stage study for ALN-TTRsc will test patients with FAC.

Less than two weeks ago, Alnylam presented positive top-line data from a mid-stage study for ALN-TTR02, the intravenous version of ALN-TTRsc. Alnylam is planning an extension study of the drug that will test patients over the course of two years.

Sanofi’s Genzyme unit holds Asian rights to Alnylam’s broader ALN-TTR program, which includes ALN-TTR02 and ANT-TTRsc. Alnylam has the rights to sell the drug, should it make it through clinical trials and win approval from regulators, in the rest of the world.

Isis Pharmaceuticals (NASDAQ: ISIS) and GlaxoSmithKline (NYSE: GSK) are co-developing a rival drug for TTR amyloidosis. Isis and GSK started a Phase 2/3 clinical trial for the drug, known as ISIS-TTRrx, in February.