Alnylam heralds positive results for RNAi amyloidosis drug

Alnylam Pharmaceuticals ($ALNY), a specialist in RNAi drug delivery, welcomed positive results in an early-stage trial of its treatment designed to silence the gene that causes a rare, deadly form of the disease amyloidosis. The data establish human translation for Alnylam's conjugate delivery platform, the company says.

TTR-mediated amyloidosis (ATTR) is caused by a mutation in the transthyretin (TTR) gene. The disease is inherited, progressively debilitating and fatal, affecting about 50,000 people worldwide. For the 40,000 patients who have the more serious form of the disease, which carries a mean survival of about two and half years, there is no approved therapy, according to Alnylam. For 10,000 more with the still deadly but less severe form of ATTR, the only treatment options currently are liver transplantation or the drug tafamidis, which is only approved in Europe.

So when the Cambridge-based company showed in a Phase I trial that its RNAi drug ALN-TTRsc achieved up to 94% knockdown of serum TTR protein levels, according to data presented Monday at the Heart Failure Society of America's 17th Annual Scientific Meeting in Orlando, FL, it heralded the results as a clear benchmark in treating the deadly disease.

Furthermore, the results confirm that GalNAc-siRNA conjugates, the company's delivery platform for RNA drugs, can be used in human patients through subcutaneous delivery. The trouble with RNA drugs since their Nobel Prize-winning discovery in 2006 has been in delivering them safely and effectively to the genetic material within cells.

And Alnylam's future depends entirely on these positive results--it has several more RNAi drugs in clinical and preclinical trials, as well as alliances with biotech and pharma giants Merck ($MRK), Medtronic ($MDT), Novartis ($NVS), Biogen Idec ($BIIB), Roche ($RHHBY), Takeda, Genzyme and others based on the success of its RNAi platform.

"These new ALN-TTRsc results are a major milestone in our ATTR program, as well as our entire pipeline of RNAi therapeutics," Alnylam executive vice president and chief medical officer Akshay Vaishnaw said in a statement. "Specifically, we have demonstrated robust, up to 94% knockdown of circulating TTR with a very encouraging safety profile. We believe this level of consistent TTR knockdown is exceptional and unmatched, and we now aim to advance ALN-TTRsc in future clinical studies with the goal of achieving approximately 90% TTR knockdown to maximize clinical efficacy."

A company spokesperson told FierceDrugDelivery in an email that Alnylam plans to begin a Phase II study by the end of 2013 and, with positive results there, a pivotal Phase III trial by the end of 2014.

- here's the release