Alnylam Receives Approval of ONPATTROTM (patisiran) in Europe

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that the European Commission (EC) has granted marketing authorization for ONPATTROTM (patisiran) for the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis in adults with stage 1 or stage 2 polyneuropathy.

ONPATTRO is based on Nobel Prize-winning science and is the first-ever RNA interference (RNAi) therapeutic to be approved in the European Union. 

“Today’s approval is the result of many years of dedicated effort and marks the next step towards bringing a potentially life-changing treatment to patients with hATTR amyloidosis and their families. Patisiran has been shown to improve polyneuropathy, quality of life and activities of daily living,” said Theresa Heggie, Head of Europe, Alnylam Pharmaceuticals.

“This is the start of a new chapter in the treatment of this rare, rapidly progressive, fatal disease. We want to express our profound gratitude to the patients who participated in the patisiran clinical trials and their families and caregivers who supported them, as well as the investigators and study staff, without whom this important milestone would not have been achieved. We look forward to applying our innovative
therapeutic approach to help patients with other rare diseases in the future.”

“Until recently, patients diagnosed with hereditary ATTR amyloidosis faced an uncertain future. A lack of treatments to halt or reverse the progression of disease resulted in a gradual and inescapable decline in their day-to-day functioning, placing a heavy burden not just on the patient themselves but on their partners and families, many of whom end up being full time carers,” said Professor Philip N. Hawkins, Ph.D, FRCP, FRCPath, FMedSci, National Amyloidosis Centre, Division of Medicine, and University College London Medical School, Royal Free Hospital, UK.

“Patisiran has the potential not only to transform these patients’ lives but to change the way in which we think about and treat hereditary ATTR amyloidosis.”

Many serious, chronic and life-threatening diseases, such as hATTR amyloidosis, are caused by a fault or mutation that interferes with the way the body manufactures proteins. RNAi is a completely
new approach to the treatment of these diseases; targeting the faulty protein that is causing the disease rather than treating the symptoms. RNAi therapeutics are an entirely new class of medicines.

The EC decision was based on the evaluation of the effects of patisiran in hATTR amyloidosis patients with polyneuropathy and its safety profile as demonstrated in the APOLLO Phase 3 study. The Summary of Product Characteristics (SmPC) includes data from APOLLO on primary and secondary endpoints, as well as exploratory cardiac endpoints. The European Medicines Agency reviewed patisiran under the accelerated assessment procedure that is granted to medicines judged to be of major interest for public health and therapeutic innovation.

About APOLLO
The marketing authorization for patisiran was based on positive results from the randomized, double-blind, placebo-controlled, global Phase 3 APOLLO study, the largest-ever study in hATTR amyloidosis patients with polyneuropathy. Results from the APOLLO study were published in the July 5, 2018, issue of The New England Journal of Medicine.

In APOLLO, the safety and efficacy of patisiran 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 patisiran (0.3 mg per kg 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 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 patisiran 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 patisiran-treated patients experienced a treatment benefit relative to placebo, 56 percent of patisiran-treated patients at 18 months of treatment experienced improvement 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 patisiran 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 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 secondary 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 the prespecified subpopulation of 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 oedema and infusion-related reactions. To reduce the risk of infusion-related reactions, patients received premedications prior to infusion.

For ONPATTROTM prescribing information in the EU, please visit the EMA Summary of Opinion.