Tekmira Pharmaceuticals said today it received a $5 million milestone payment from Alnylam Pharmaceuticals for launching Phase III trials of patisiran (ALN-TTR02), an intravenously delivered RNAi therapeutic for TTR-mediated amyloidosis (ATTR) that uses Tekmira’s lipid nanoparticle (LNP) drug-delivery technology.
The APOLLO Phase III trial (NCT01960348), now open for enrollment, is designed to assess the efficacy and safety of patisiran in patients with familial amyloidotic polyneuropathy (FAP). The randomized, double-blind study has as its primary endpoint the difference in the change in composite neurological impairment score (NIS+7) between patisiran and placebo at 18 months.
Secondary endpoints include: the Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) score; NIS-weakness; modified BMI; timed 10-meter walk; and the COMPASS-31 autonomic symptom score. The trial is designed to enroll up to 200 FAP patients with a baseline NIS in the range of 10 to 100, which represents patients with stage 1 or stage 2 disease.
Patisiran’s advancement to Phase III comes a month after Alnylam presented positive Phase II data at the International Symposium on FAP. The data showed that multiple doses of patisiran led to robust and statistically significant knockdown of serum TTR protein levels of up to 96% in ATTR patients, with mean levels of TTR knockdown exceeding 85%. Knockdown of TTR was found to be rapid, dose dependent, and durable, with similar activity seen toward both wild-type and mutant protein. Multiple doses of patisiran were found to be generally safe and well tolerated.
The $5 million payment represents half the $10 million in milestone payments to which Tekmira is eligible, based on advancement of not only patisiran but ALN-VSP, a treatment candidate for liver cancers and potentially other solid tumors with liver involvement.
The $10 million was part of a larger settlement between the companies last year that resolved nearly two years of patent litigation over LNP. Alnylam agreed to pay Tekmira $30 million to secure rights to manufacture its own LNP-based products in the future, either on its own or through a third party. Alnylam said at the time it would use the cash to advance patisiran. In addition, Alnlyam agreed to pay $35 million to buy down its milestone and royalty payments owed Tekmira for ALN-TTR02, ALN-VSP, and a third drug candidate, ALN-PCS for high levels of cholesterol in the blood.
Alnylam took a $65 million charge against Q4 2012 operating expenses to reflect the settlement and restructuring of licensing agreements with Tekmira.
Tekmira is also entitled to ongoing royalties related to patisiran and other LNP-enabled products upon commercialization.
Patisiran is one of five RNAi therapeutics Alnylam has committed itself to developing by 2015 under its “Alnylam 5x15™” product strategy. 5x15 focuses on clinical development (including advanced stages), by itself or with partners, of “innovative” RNAi therapeutics for genetically defined diseases addressing major unmet medical needs.