Alnylam Pharmaceuticals, Inc., the leading RNAi therapeutics company, announced today positive topline results from the interim analysis of the ENVISION Phase 3 Study of givosiran, an investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyria (AHP). The pre-specified interim analysis was based on lowering of urinary ALA levels as a surrogate biomarker that is reasonably likely to predict clinical benefit.
Results of the interim analysis showed that givosiran treatment was associated with a statistically significant reduction in urinary ALA levels in acute intermittent porphyria (AIP) patients, relative to placebo (p less than 0.001). The Company plans to discuss these data and the regulatory path forward with the FDA, and, pending the outcome of those discussions, intends to file a New Drug Application (NDA) at or around year-end 2018 in support of a potential Accelerated Approval. The interim analysis had a data cut-off date of August 22, 2018 and included 43 patients with AHPs (41 patients with AIP, one with variegate porphyria [VP], and one with hereditary coproporphyria [HCP]) who were on study for at least three months. As of the data cut-off date, there were no deaths, and serious adverse events (SAEs) were reported in 22 percent (5/23) of givosiran patients and 10 percent (2/20) of placebo patients. One patient (4 percent) on givosiran discontinued treatment due to an increase in liver transaminase - which resolved - that was greater than eight times the upper limit of normal (ULN), a protocol-defined stopping rule. There were no treatment discontinuations in the placebo group.
"The AHPs are devastating diseases in which patients suffer from both debilitating neurovisceral attacks as well as chronic pain and fatigue. We are pleased and encouraged that the interim analysis of the ENVISION Phase 3 study demonstrated that givosiran treatment was associated with statistically significant lowering of ALA, a disease biomarker reasonably likely to predict clinical benefit," said Akshay Vaishnaw, M.D., Ph.D., President of Research and Development at Alnylam. "With these interim results in hand, we plan to meet with the FDA to discuss the results and the overall benefit-risk profile for a potential NDA submission at or around year-end in support of an Accelerated Approval. In the meantime, with enrollment in ENVISION completed ahead of schedule, we look forward to reporting topline results for the full study early next year. If clinical efficacy and acceptable safety are confirmed in the full study, we believe givosiran has the potential to transform the lives of patients living with an AHP."
Alnylam continues to dose patients in the ongoing ENVISION study, where enrollment was completed ahead of schedule with 94 AHP patients. The Company expects to report topline full study results of the primary endpoint - the annualized attack rate after six months of treatment - in early 2019.