Benzinga | Oct 27, 2021 04:15PM EDT

Alnylam Reports Topline 18-Month Results From HELIOS-A Phase 3 Study Of Vutrisiran In Patients With hATTR Amyloidosis With Polyneuropathy

-- Vutrisiran Met All 18-Month Secondary Endpoints, Including Statistically Significant Improvements in Progression of Neuropathy, Quality of Life (QOL), Gait Speed, Nutritional Status and Overall Disability, Relative to External Placebo --

-- At Month 18, Vutrisiran Also Showed Improvements in Exploratory Endpoints, Including Technetium Uptake Relative to Baseline in a Planned Cohort, Providing Potential Evidence for Reduced Cardiac Amyloid Burden --

-- In Addition, Vutrisiran Continued to Demonstrate an Encouraging Safety and Tolerability Profile --

-- Alnylam Intends to Present Full HELIOS-A 18-Month Results at a Medical Congress in Early 2022 --

-- Alnylam to Discuss Data as Part of Third Quarter 2021 Financial Results Conference Call to be Held Tomorrow, October 28 at 8:30 am ET --

Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY), the leading RNAi therapeutics company, today announced that the HELIOS-A Phase 3 study of vutrisiran, an investigational RNAi therapeutic in development for the treatment of the polyneuropathy associated with hereditary transthyretin-mediated (hATTR) amyloidosis, met all secondary endpoints measured at 18 months, including statistically significant improvements in neuropathy as measured by the modified Neuropathy Impairment Score (mNIS+7), quality of life (QOL), gait speed, nutritional status and overall disability, relative to external placebo data from the APOLLO Phase 3 study of patisiran. The final secondary endpoint, reduction in serum TTR levels with vutrisiran, demonstrated non-inferiority relative to the within-study patisiran arm, as expected. In addition, patients treated with vutrisiran showed improvements in exploratory endpoints, including the biomarker NT-proBNP and certain echocardiographic parameters, relative to placebo, and an improvement in technetium uptake relative to baseline in a majority of patients in a planned cohort, providing potential evidence for reduced cardiac amyloid burden. Vutrisiran continued to demonstrate an encouraging safety and tolerability profile. Alnylam previously announced that HELIOS-A met its primary and secondary endpoints at nine months and study results were presented at the 2021 American Academy of Neurology (AAN) Virtual Annual Meeting.

"These results build on the positive vutrisiran data shared earlier this year and suggest that the reduction of neurologic impairment and improvement in quality of life in patients with hATTR amyloidosis with polyneuropathy observed as early as nine months are maintained at 18 months. We are also encouraged by the hypothesis-supporting, exploratory endpoints and cardiac amyloid imaging results," said Rena N. Denoncourt, Vice President, TTR Franchise Lead. "Vutrisiran is currently under review by multiple regulatory authorities around the world, bringing this low-dose, once-quarterly, subcutaneously administered investigational therapy with a highly-attractive profile one step closer to being a potentially available therapeutic option for patients living with this progressive, life-threatening, multi-system disease. We look forward to presenting full 18-month results of the HELIOS-A study at a medical conference in early 2022, and progressing our efforts to build an industry-leading franchise of medicines for the treatment of the polyneuropathy of hATTR amyloidosis and potentially additional indications for the future."

At 18 months, patients treated with vutrisiran showed quantitative improvement across a number of exploratory endpoints. Compared to placebo, patients in the vutrisiran arm demonstrated improvement in the cardiac biomarker endpoint, NT-proBNP, a measure of cardiac stress. In addition, patients treated with vutrisiran also demonstrated improvement in certain echocardiographic parameters, relative to placebo. Finally, in a planned cohort of 48 patients, treatment with vutrisiran was associated with an improvement in technetium uptake in the heart in a majority of patients, providing potential evidence for reduced cardiac amyloid burden.

Vutrisiran demonstrated an encouraging safety profile. There were three study discontinuations (2.5 percent) due to adverse events in the vutrisiran arm during the 18 Month treatment period; the single new discontinuation since Month 9 was an event of cardiac failure considered unrelated to study drug by the investigator. During the 18 Month treatment period, there were two deaths (neither of which was considered related to study drug) and two serious adverse events (SAEs) deemed related to vutrisiran by the study investigator; these deaths and related SAEs all occurred by Month 9 and were previously reported. Treatment emergent adverse events (AEs) occurring in 10 percent or more patients included fall, pain in extremity, diarrhea, peripheral edema, urinary tract infection, arthralgia and dizziness; with the exception of pain in extremity and arthralgia, each of these events occurred at a similar or lower rate as compared with external placebo. Injection site reactions (ISRs) were reported in 5 patients (4.1 percent) and were all mild and transient. There were no hepatic safety concerns.

Vutrisiran is under review by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Brazilian Health Regulatory Agency (ANVISA). Vutrisiran has been granted Orphan Drug Designation in the U.S. and the European Union (EU) for the treatment of ATTR amyloidosis. Vutrisiran has also been granted a Fast Track designation in the U.S. for the treatment of the polyneuropathy of hATTR amyloidosis in adults. In the U.S., vutrisiran has received an action date under the Prescription Drug User Fee Act (PDUFA) of April 14, 2022. The Company received Orphan Drug Designation in Japan for transthyretin type familial amyloidosis with polyneuropathy.