Alnylam Receives Positive CHMP Opinion for ONPATTRO™ (patisiran) for the Treatment of Hereditary Transthyretin-Mediated Amyloidosis in Adults with Stage 1 or Stage 2 Polyneuropathy
– European Commission Decision Expected in September –
– Recommended Summary of Product Characteristics (SmPC) Includes Data on Secondary and Exploratory Endpoints, Including Results on Cardiac Parameters –
“We are delighted with this positive opinion, and today’s recommendation
by the CHMP takes us one step closer to bringing RNAi therapeutics, an
entirely new class of innovative medicines, to patients around the
“hATTR amyloidosis is a progressively debilitating disease that often
impacts patients and their families in the prime of their lives,” said
The CHMP positive opinion is based on the evaluation of the effects of
patisiran in patients with hATTR amyloidosis and its safety profile as
demonstrated in the APOLLO Phase 3 study. The SmPC recommended by the
CHMP includes data from APOLLO primary and secondary endpoints, as well
as exploratory cardiac endpoints. The results of the APOLLO study were
In APOLLO, the safety and efficacy of patisiran were evaluated in a diverse, global population of hATTR amyloidosis patients. Patients were randomized in a 2:1 ratio to receive intravenous patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks for 18 months. The study showed that patisiran 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. The APOLLO study used the modified Neuropathy Impairment Score +7 (mNIS+7) to assess motor strength, reflexes, sensation, nerve conduction and postural blood pressure.
- Patients treated with patisiran had a mean 6.0-point decrease (improvement) in mNIS+7 score from baseline compared to a 28.0-point mean increase (worsening) for patients in the placebo group, resulting in a 34.0-point mean difference relative to placebo, after 18 months of treatment.
- While nearly all patisiran-treated patients experienced a treatment benefit relative to placebo, 56 percent of patisiran-treated patients experienced significant improvement in measures of their polyneuropathy (as assessed by mNIS+7 score) relative to their own baseline with 18 months of treatment, compared to four percent of patients who received placebo.
- As measured by the Norfolk Quality of Life Diabetic Neuropathy (QoL-DN) Score, 51 percent of patients treated with patisiran 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 patisiran experienced significant benefit vs. placebo for all other efficacy endpoints including measures of activities of daily living, walking ability, nutritional status, and autonomic symptoms.
- Patisiran was associated with favorable effects on exploratory endpoints related to cardiac structure and function in patients with cardiac involvement.
- The incidence and severity of adverse events were similar in patients receiving patisiran and placebo. The most common adverse events that occurred more frequently with patisiran than with placebo were peripheral edema and infusion-related reactions.
Patisiran is an investigational, intravenously administered RNAi therapeutic targeting transthyretin (TTR) in development for the treatment of hereditary ATTR amyloidosis. It is designed to target and silence specific messenger RNA, potentially blocking the production of TTR protein before it is made. This may help to reduce the deposition and facilitate the clearance of TTR amyloid in peripheral tissues and potentially restore function to these tissues.
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, affecting approximately 50,000 people worldwide. The median survival is 4.7 years following diagnosis, with a reduced survival (3.4 years) for patients presenting with cardiomyopathy. In
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. By harnessing the natural biological process of RNAi occurring in our cells, a major new class of medicines, known as RNAi therapeutics, is on the horizon. 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 with the potential to transform 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 data supporting the CHMP positive opinion, recommended SmPC, and ongoing regulatory reviews of patisiran, the potential implications of such data for patients, the commercial readiness of Alnylam to launch patisiran in
None of Alnylam’s investigational therapeutics have been approved by the
Alnylam Pharmaceuticals, Inc.
Christine Regan Lindenboom, +1-617-682-4340
(Investors and Media)
Josh Brodsky, +1-617-551-8276
Fiona McMillan, +44 1628 244960