Alnylam Pharmaceuticals has been trying to shift from a technology platform company into a more mature drug developer the past few years. Today its shares climbed more than 40 percent as it got some stronger signs that it could be on track to make its first marketable drug, for a rare disease called TTR amyloidosis.
The Cambridge, MA-based company (NASDAQ: ALNY), which makes RNA interference medicines, said today its ALN-TTR02 experimental treatment was able to reduce the amount of TTR proteins circulating in the blood by as much as 94 percent. The study, of 17 healthy volunteers in the U.K., showed that the Alnylam drug knocked down TTR quickly, that higher doses produced a greater effect than low doses, and the knockdown lasted at least a month after a single shot. The drug appeared safe and well-tolerated, although one patient on a high dose had an acute infusion reaction, which was resolved when the infusion rate was slowed down. Results were reported today in a seminar at Boston University School of Medicine.
Based on the findings, Alnylam is moving ahead into a mid-stage clinical trial with the new drug, and said it should be ready by early 2013 to enter the third and final phase of studies required for FDA approval. Alnylam delivered the first evidence to suggest an RNAi drug could be effective against TTR amyloidosis last fall, but today’s results come from Alnylam’s use of a second-generation lipid nanoparticle to deliver the drug inside cells, which is designed to be 10 times more potent. If Alnylam can reproduce the findings in the next set of clinical trials, it could have its first new RNAi-based product to market. About 8,000 people around the world have a form of TTR amyloidosis that damages the nerves, while about 40,000 have a form that harms the heart.
“I am impressed with the almost complete knockdown of TTR after just a single dose of drug, which is important since TTR protein reduction in patients with [TTR amyloidosis] has the potential to delay or even reverse disease progression with associated clinical benefits,” said Teresa Coelho, the Director of Unidade Clinica de Paramiloidose, in an Alnylam statement.
The disease, transthyretin (TTR) amyloidosis, allows excessive amounts of amyloid proteins to build up in tissues throughout the body. Alnylam likes going after this disease partly because it’s a single gene disorder of the TTR protein, and the protein in question is concentrated in the liver, where RNAi therapeutics can be delivered. People typically start developing symptoms of this disease in their 30s and 40s, suffer progressive damage to their nerves and heart, and usually live nine to 11 years after symptoms appear, Alnylam has said.
Shares of Alnylam climbed 44 percent to $17.96 at 1:07 pm Eastern time.
While knocking down TTR is an encouraging sign that the Alnylam drug is working, it’s more of a scientific indicator, and not the gold standard measurement for success in clinical trials. Since TTR amyloidosis is a chronic condition, Alnylam will need to show that it can safely deliver its drug on a repeat basis. And as CEO John Maraganore discussed with Xconomy in an interview in December, future clinical trials will likely be judged by a different score, something called Neuropathy Impairment Score – Lower Limb, or NIS-LL, which measures neurological function in the legs. Alnylam is also mired in an intellectual property dispute with Vancouver, BC-based Tekmira Pharmaceuticals, which argues that it owns the second-generation lipid nanoparticle delivery technology.
For more of the details on how each group of volunteers performed in the study, see Alnylam’s release.