Alnylam completes enrollment in APOLLO phase 3 study with Patisiran in rare protein disorder

The Company also reiterated its previous guidance that it expects to report data from the APOLLO study in 2017, and due to the competitiveness of this timing, it is not planning to perform an interim analysis for efficacy.

If APOLLO is positive, the Company expects to submit a New Drug Application (NDA) and Marketing Authorisation Application (MAA) for patisiran, based on an analysis of the full APOLLO data set, in late 2017.

ATTR amyloidosis is an inherited, progressive, and life-threatening orphan disease affecting approximately 50,000 patients worldwide, including approximately 10,000 persons with FAP. Halting disease progression remains the primary treatment goal and represents a significant unmet need.

Eric Green, vice president and general manager of TTR program, said: "ATTR amyloidosis, including FAP, is a generally fatal, orphan disease with limited treatment options. We believe data reported to date in our clinical studies provide encouraging preliminary evidence for patisiran’s clinical activity and tolerability, while definitive evidence to support registration awaits results from our randomized, placebo-controlled study. Accordingly, we’re excited to have rapidly completed enrollment in our APOLLO Phase 3 study.

"We’re also pleased to see the strong patient interest in patisiran, with APOLLO significantly over-enrolled. Regarding our decision to forego an interim analysis for efficacy, our timely and highly competitive completion of APOLLO enrollment supports our continued plan to file an NDA and MAA with a full and comprehensive analysis of primary and secondary endpoint data in 2017, if the study is positive."

The APOLLO Phase 3 trial is a randomized, double-blind, placebo-controlled, global study designed to evaluate the efficacy and safety of patisiran in patients with FAP. The primary endpoint of the study is the difference in the change in a modified neuropathy impairment score, "mNIS+7," from baseline to 18 months between patisiran and placebo. mNIS+7 measures disease progression including muscle weakness, impaired reflexes, and changes in other sensory measures.

Secondary study endpoints include: the Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) score; modified body mass index (mBMI); timed 10-meter walk; an autonomic symptom score called "COMPASS-31," amongst other endpoints. In addition, nerve regeneration by measurement of sweat gland nerve fiber density will be assessed in patients who elected to provide skin punch biopsy samples.

The study was significantly over-enrolled with a total of 225 FAP patients with Stage 1 or Stage 2 disease, compared to the original anticipated enrollment of 200. Patients were randomized 2:1 (patisiran:placebo) with patisiran administered at 0.30 mg/kg once every three weeks for 18 months.

The study was designed with 90% power to conservatively detect as little as a 37.5% difference in change in mNIS+7 between treatment groups, with a two-sided alpha of 0.05. The expected placebo mNIS+7 progression rate of 24 points over 18 months was derived from an analysis of natural history data from 283 FAP patients (Adams et al., Neurology, 2015;85:675-682). All patients completing the APOLLO Phase 3 study are eligible to enroll in the ongoing APOLLO Phase 3 open-label extension (OLE) study (APOLLO-OLE).

In an ongoing Phase 2 OLE study of patisiran in FAP patients (N=27) with similar baseline characteristics, patisiran administration was associated with a mean increase in mNIS+7 of just 1.7 points over 18 months in the 20 patients that had reached that timepoint as of the data cutoff.

The ongoing Phase 2 OLE study has provided initial evidence that patisiran has the potential to halt neuropathy progression in FAP patients, including the first-ever evidence for positive effects on nerve regeneration. Patisiran administration was also found to be generally well tolerated in FAP patients out to nearly two years, with minimal drug-related adverse events reported.