Alnylam Presents Positive Results from HELIOS-A Phase 3 Study of Investigational Vutrisiran
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc.?(Nasdaq: ALNY), the leading RNAi therapeutics company, today announced full positive results from the HELIOS-A Phase 3 study of vutrisiran, an investigational RNAi therapeutic in development for the treatment of transthyretin-mediated (ATTR) amyloidosis, which met its primary and both secondary endpoints at nine months in patients with hereditary ATTR (hATTR) amyloidosis with polyneuropathy. The results were presented today in an oral session at the 2021 American Academy of Neurology (AAN) Virtual Annual Meeting.
The 9-month results achieved the study?s primary endpoint, with vutrisiran showing improvement in the mean change from baseline in the modified Neuropathy Impairment Score (mNIS+7) as compared to external placebo data from the APOLLO Phase 3 study of patisiran. At 9 months vutrisiran also met all secondary endpoints, demonstrating improvement in quality of life as assessed by the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) instrument and improvement in gait speed as assessed by the timed 10-meter walk test (10-MWT), both compared to the external placebo group. The majority of patients experienced improvement in neuropathy and in quality of life, both relative to baseline, showing the potential for vutrisiran to reverse polyneuropathy manifestations of hATTR amyloidosis. Vutrisiran also demonstrated an encouraging safety profile with no drug-related discontinuations or deaths. Based on these positive data, Alnylam has submitted a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) for the approval of vutrisiran for the treatment of the polyneuropathy of hATTR amyloidosis in adults.
?The HELIOS-A study results demonstrate that vutrisiran improves neuropathy, quality of life and gait speed as soon as 9 months ? compared to the external placebo arm of APOLLO ? in patients with hATTR amyloidosis with polyneuropathy, with an encouraging safety and tolerability profile. The reversal of polyneuropathy manifestations of disease demonstrated in patients treated with vutrisiran in the study, the encouraging safety profile, and the totality of data from the trial, reinforce our belief in the promise of our RNAi therapeutics? mechanism of action, as first established with ONPATTRO??(patisiran). Further, we are encouraged by the exploratory endpoint results showing the impact of vutrisiran on NT-proBNP, a marker of cardiac stress, and look forward to additional data on exploratory cardiac endpoints at the 18-month readout, expected in late 2021,? said Akshay Vaishnaw, M.D., Ph.D., President of R&D?at Alnylam. ?With our NDA filing now completed, we look forward to potentially bringing vutrisiran to patients as a new treatment option for the polyneuropathy of hATTR amyloidosis with subcutaneous administration and quarterly dosing. The positive HELIOS-A study and our NDA filing are key milestones as we continue our progress towards building an industry-leading franchise of medicines for the treatment of ATTR amyloidosis and towards our goal of expanding in the future the population of patients who may benefit from treatment with an RNAi therapeutic.?
HELIOS-A Study Results
At 9 months, vutrisiran met the primary and all secondary endpoints in HELIOS-A, specifically:
- Vutrisiran achieved a rapid and sustained reduction in serum TTR levels with an 83 percent mean steady-state serum TTR reduction from baseline.
- Consistent results in serum TTR level reduction were observed between the vutrisiran and patisiran arms of HELIOS-A, aligned with the therapeutic hypothesis.
- Vutrisiran treatment (N=122) resulted in a 2.24 point mean decrease (improvement) in mNIS+7 score from baseline at 9 months as compared to a 14.76 point mean increase (worsening) reported for the external placebo group (N=77), resulting in a 17.0 point mean difference relative to placebo (p equal to 3.54x10-12).
- Improvement in mNIS+7 from vutrisiran treatment was also consistently observed across all pre-specified patient subgroups, including age, sex, race, geographic region, baseline neuropathy impairment, genotype, prior TTR stabilizer use, baseline Familial Amyloid Polyneuropathy (FAP) stage, and inclusion in the pre-specified cardiac subpopulation.
- Patients randomized to the patisiran reference arm in HELIOS-A showed results consistent with the vutrisiran arm.
- Vutrisiran treatment resulted in a 3.3 point mean decrease (improvement) in Norfolk QoL-DN score from baseline at 9 months as compared to a 12.9 point mean increase (worsening) reported for the external placebo group, resulting in a mean 16.2 point difference relative to placebo (p equal to 5.43x10-9).
- Patients treated with vutrisiran remained stable in gait speed (mean decrease of 0.001 meters/second in 10-MWT), while patients in the external placebo group demonstrated worsening (mean decrease of 0.133 meters/second in 10-MWT) (p equal to 3.10x10-5).
- Improvement in the exploratory cardiac endpoint, NT-proBNP, a measure of cardiac stress, was observed in the vutrisiran arm in both the pre-specified cardiac sub-population and the modified intent-to-treat (mITT) population, relative to the external placebo group.
- The cardiac subpopulation was defined as patients who had pre-existing evidence of cardiac amyloid involvement (baseline left ventricular wall thickness =1.3 cm and no aortic valve disease or hypertension in medical history). NT-proBNP adjusted geometric fold change from baseline was 0.95 for the vutrisiran cardiac subpopulation group (N=35) and 1.60 for the external placebo cardiac subpopulation (N=34) group, with an adjusted geometric fold change ratio of 0.60 (p equal to 0.0016)?in favor of vutrisiran.
- Similar results from baseline were seen in the mITT population in favor of vutrisiran relative to the external placebo group (p equal to 9.20x10-7).
- In addition, vutrisiran demonstrated improvements in other exploratory endpoints measured at 9 months, including change from baseline in modified body mass index (mBMI) and the Rasch-built overall disability scale (R-ODS), relative to external placebo.