Alnylam Announces First-Ever FDA Approval of an RNAi Therapeutic, ONPATTRO™ (patisiran) for the Treatment of the Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis in Adults
− First and Only FDA-approved Treatment Available in
− ONPATTRO Shown to Improve Polyneuropathy Relative to Placebo, with Reversal of Neuropathy Impairment Compared to Baseline in Majority of Patients –
− Improvement in Specified Measures of Quality of Life and Disease Burden Demonstrated Across Diverse, Global Patient Population –
− Alnylam to Host Conference Call Today at
This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20180810005398/en/
ONPATTRO™ (patisiran) packaging and product vial (Photo: Business Wire)
“Alnylam was founded on the vision of harnessing the potential of RNAi
therapeutics to treat human disease, and this approval heralds the
arrival of an entirely new class of medicines. We believe today draws us
ever-closer to achieving our Alnylam 2020 goals of becoming a
fully integrated, multi-product biopharmaceutical company with a
sustainable pipeline,” said
“Today’s historic approval marks the arrival of a first-of-its kind
treatment option for a rare and devastating condition with limited
treatment options,” said Akshay Vaishnaw, M.D., Ph.D., President of R&D
at Alnylam. “We extend our deepest gratitude to the patients who
participated in the ONPATTRO clinical trials and their families and
caregivers who supported them. We are also grateful for the tireless
efforts of the investigators and study staff, without whom this
important milestone would not have been possible. We also look forward
to working with the
In APOLLO, the safety and efficacy of ONPATTRO were evaluated in a diverse, global population of hATTR amyloidosis patients in 19 countries, with a total of 39 TTR mutations. Patients were randomized in a 2:1 ratio to receive intravenous ONPATTRO (0.3 mg per kg of body weight) or placebo once every 3 weeks for 18 months. The study showed that ONPATTRO improved measures of polyneuropathy, quality of life, activities of daily living, ambulation, nutritional status and autonomic symptoms relative to placebo in adult patients with hATTR amyloidosis with polyneuropathy. The primary endpoint of the APOLLO study was the modified Neuropathy Impairment Score +7 (mNIS+7), which assesses motor strength, reflexes, sensation, nerve conduction and postural blood pressure.
- Patients treated with ONPATTRO had a mean 6.0-point decrease (improvement) in mNIS+7 score from baseline compared to a mean 28.0-point increase (worsening) for patients in the placebo group, resulting in a mean 34.0-point difference relative to placebo, after 18 months of treatment.
- While nearly all ONPATTRO-treated patients experienced a treatment benefit relative to placebo, 56 percent of ONPATTRO-treated patients at 18 months of treatment experienced reversal of neuropathy impairment (as assessed by mNIS+7 score) relative to their own baseline, compared to four percent of patients who received placebo.
- Patients treated with ONPATTRO had a mean 6.7-point decrease (improvement) in Norfolk Quality of Life Diabetic Neuropathy (QoL-DN) score from baseline compared to a mean 14.4-point increase (worsening) for patients in the placebo group, resulting in a mean 21.1-point difference relative to placebo, after 18 months of treatment.
- As measured by Norfolk QoL-DN, 51 percent of patients treated with ONPATTRO experienced improvement in quality of life at 18 months relative to their own baseline, compared to 10 percent of the placebo-treated patients.
- Over 18 months of treatment, patients treated with ONPATTRO experienced significant benefit vs. placebo for all other secondary efficacy endpoints, including measures of activities of daily living, walking ability, nutritional status, and autonomic symptoms.
- The most common adverse events that occurred more frequently with ONPATTRO than with placebo were upper respiratory tract infections and infusion-related reactions. To reduce the risk of infusion-related reactions, patients received premedications prior to infusion.
“FDA approval of ONPATTRO represents an entirely new approach to
treating patients with polyneuropathy in hATTR amyloidosis and shows
promise as a new era in patient care,” said
“For years I have witnessed the tragic impact of hATTR amyloidosis on
generations of families. Today, we celebrate the
“Today’s approval is significant in so many respects. It means the hATTR
amyloidosis community of patients, families, caregivers and healthcare
ONPATTRO is expected to be available for shipment to healthcare providers in the U.S. within 48 hours.
Alnylam is committed to helping people access the medicines they are prescribed and will be offering comprehensive support services for people prescribed ONPATTRO through Alnylam Assist™. Visit AlnylamAssist.com for more information or call 1-833-256-2748.
ONPATTRO was reviewed by the
Conference Call Details
Alnylam management will discuss the
IMPORTANT SAFETY INFORMATION
Infusion-related reactions (IRRs) have been observed in patients treated with ONPATTRO. In a controlled clinical study, 19% of ONPATTRO-treated patients experienced IRRs, compared to 9% of placebo-treated patients. The most common symptoms of IRRs with ONPATTRO were flushing, back pain, nausea, abdominal pain, dyspnea, and headache.
To reduce the risk of IRRs, patients should receive premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) at least 60 minutes prior to ONPATTRO infusion. Monitor patients during the infusion for signs and symptoms of IRRs. If an IRR occurs, consider slowing or interrupting the infusion and instituting medical management as clinically indicated. If the infusion is interrupted, consider resuming at a slower infusion rate only if symptoms have resolved. In the case of a serious or life-threatening IRR, the infusion should be discontinued and not resumed.
Reduced Serum Vitamin A Levels and Recommended Supplementation
ONPATTRO treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking ONPATTRO. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with ONPATTRO, as serum levels do not reflect the total vitamin A in the body.
Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g. night blindness).
The most common adverse reactions that occurred in patients treated with ONPATTRO were upper respiratory tract infections (29%) and infusion related reactions (19%).
For additional information about ONPATTRO, please see the full Prescribing Information.
About ONPATTRO™ (patisiran) lipid complex injection
ONPATTRO was approved by the
About hATTR Amyloidosis
Hereditary transthyretin (TTR)-mediated amyloidosis (hATTR) is an inherited, progressively debilitating, and often fatal disease caused by mutations in the TTR gene. TTR protein is primarily produced in the liver and is normally a carrier of vitamin A. Mutations in the TTR gene cause abnormal amyloid proteins to accumulate and damage body organs and tissue, such as the peripheral nerves and heart, resulting in intractable peripheral sensory neuropathy, autonomic neuropathy, and/or cardiomyopathy, as well as other disease manifestations. hATTR amyloidosis represents a major unmet medical need with significant morbidity and mortality. The median survival is 4.7 years following diagnosis. Until now, people living with hATTR amyloidosis in the U.S. had no
As part of Alnylam’s commitment to making therapies available to those who may benefit from them, Alnylam Assist will offer a wide range of services to guide patients through treatment with ONPATTRO, including financial assistance options for eligible patients, benefit verification and claims support, and ordering assistance and facilitation of delivery via specialty distributor or specialty pharmacy. Patients will have access to dedicated Case Managers who can provide personalized support throughout the treatment process and Patient Education Liaisons to help patients gain a better understanding of the disease. Visit AlnylamAssist.com for more information.
RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. RNAi therapeutics are a new class of medicines that harness the natural biological process of RNAi. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing proteins, thus preventing them from being made. This is a revolutionary approach in developing medicines to improve the care of patients with genetic and other diseases.
Alnylam Forward Looking Statements
Various statements in this release concerning Alnylam's future expectations, plans and prospects, including, without limitation, Alnylam's views with respect to the approval of ONPATTRO™ (patisiran) lipid complex injection, including the approved indication, and the implications of such approval for patients, the results from its APOLLO Phase 3 clinical trial for patisiran, its expectations concerning when ONPATTRO will be available for shipment to healthcare providers in the U.S., its plan to offer comprehensive support services for people prescribed ONPATTRO through Alnylam Assist™, the expected timing for additional regulatory filings for approval in global markets, its expectations regarding the potential for patisiran to improve the lives of hATTR amyloidosis patients with polyneuropathy and their families, its plans to work with the
Alnylam Pharmaceuticals, Inc.
Christine Regan Lindenboom, 617-682-4340
(Investors and Media)
Josh Brodsky, 617-551-8276