25. Onpattro

John Maraganore casual
(Alnylam)

Active ingredient: patisiran
Disease: peripheral nerve disease (polyneuropathy) caused by hereditary transthyretin-mediated amyloidosis 
Peak sales estimate: $1 billion
Approved: Aug. 10
Company: Alnylam  

The scoop: The 16-year R&D quest to get Onpattro on the market, the first-ever approval for a small interfering ribonucleic acid, saw it gain a lot of love when it was approved in the summer: “Game-changing” and “a tremendous achievement” were just two of the glowing reviews from analysts, although maybe not from payers, given its $345,000-per-year price tag (after discounts, and a money-back guarantee if it doesn’t work). The so-called gene-silencing drug (here, Onpattro encases the siRNA into a lipid nanoparticle to deliver the drug directly into the liver, in an infusion treatment, to alter or halt the production of disease-causing proteins) is approved, also a first for the FDA, for patients with polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (hATTR). It can treat potentially up to 15,000 patients in the U.S. (although only around 20% are diagnosed), and there are around 50,000 patients worldwide. The biotech is eyeing blockbuster sales with the help of a big marketing push to get more patients diagnosed. But the FDA approved the drug for a smaller group of patients than investors had hoped, which hit its shares at the time and could hamper sales. And it was hit two months later by the approval of a rival drug in Ionis/Akcea’s Tegsedi, which is vying for the same patients. And Tegsedi is easier for those patients to take, given that it comes in a prefilled syringe, which patients can administer subcutaneously by themselves. In contrast, at the same annual list price, Alnylam’s Onpattro needs to be given intravenously by a trained medical professional once every three weeks. There could be even more competition in the near future in the shape of Pfizer’s tafamidis, a drug that wants to cover both ATTR and its sister disease, wild-type TTR, and could also include polyneuropathy. — Ben Adams 

25. Onpattro