CAMBRIDGE - Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced that the European Commission (EC) has granted marketing authorization for GIVLAARI (givosiran), an injection for subcutaneous use targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyria (AHP) in adults and adolescents aged 12 years and older.

AHP is an ultra-rare condition in which patients can experience debilitating attacks of severe abdominal pain, vomiting and seizures, which can be life-threatening due to the possibility of paralysis and respiratory arrest during attacks. Many patients also experience chronic symptoms, including pain, which continue to be present between attacks.

'Today's approval of GIVLAARI marks a historic moment for patients and families living with this devastating genetic disease, as there are currently no approved medicines in Europe proven to decrease the frequency of attacks and reduce the chronic pain that many patients suffer,' said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. 'We are proud to bring GIVLAARI, our second RNAi medicine to be approved in the last 18 months, to patients in Europe and we want to thank the patients, families, investigators and study staff whose support and involvement have made this achievement possible.'

'The fear of not knowing when an attack will strike, combined with ongoing symptoms between attacks, affects every aspect of patients' lives, limiting their ability to work and maintain a social life,' said Dr Eliane Sardh, Head of the Porphyria Centre Sweden, Karolinska University Hospital, Sweden. 'In our experience, life is very different for patients since they have been treated with givosiran. In addition to a reduction in the number of porphyria attacks which require hospitalization and urgent healthcare visits, we have seen improvements in how patients report their overall health status and quality of life, so this approval is truly meaningful for patients, their families and the healthcare professionals who treat them. Some of our patients have been able to achieve significant personal and professional milestones that would not have been possible before.'

'We are committed to bringing GIVLAARI to patients in Europe as rapidly as possible, and plan to build on our experience in the U.S. by proactively engaging with national authorities in Europe around a value-based agreement framework which we hope will accelerate patient and provider access to GIVLAARI,' said Barry Greene, President, Alnylam. 'While every country has its own process for measuring the value of new medicines, we believe this framework will appeal in many countries as it combines payment based on performance with additional financial mechanisms to ensure the long-term financial sustainability of the treatment of all AHP patients in line with the authorized indication of GIVLAARI.'

GIVLAARI (givosiran) was granted Priority Medicines (PRIME) Designation by the European Medicines Agency (EMA) as well as Orphan Designation in the European Union. GIVLAARI was also granted an accelerated assessment, which is awarded to medicines deemed to be of major public health interest and therapeutic innovation, and the award is designed to bring new treatments to patients more quickly. This EC approval follows the recent approval of GIVLAARI by the U.S. Food and Drug Administration in November 2019. Givosiran is also awaiting approval in Brazil where it is under priority review.

About ENVISION Phase 3 Study

The marketing authorization was based on positive data from the ENVISION Phase 3 trial, a randomized, double-blind, placebo-controlled, global, multicenter study to evaluate the efficacy and safety of givosiran in patients with a documented diagnosis of acute hepatic porphyria (AHP). The primary endpoint was reduction relative to placebo in the annualized rate of composite porphyria attacks, defined as those requiring hospitalization, urgent healthcare visit, or intravenous hemin administration at home, in patients with acute intermittent porphyria (AIP, the most common subtype of AHP) over six months. The trial enrolled 94 patients with AHP, at 36 study sites in 18 countries around the world and is the largest ever interventional study conducted in AHP. Patients were randomized 1:1 to givosiran or placebo, with givosiran administered subcutaneously at 2.5 mg/kg monthly. Upon completion of dosing in the double-blind period, all eligible patients (99%) enrolled in the ENVISION open-label extension (OLE) to receive givosiran on an ongoing basis.

In the study, givosiran demonstrated a 74% reduction in the annualized composite rate of porphyria attacks in AIP patients relative to placebo.

50% of patients on givosiran were attack-free during the six-month treatment period as compared to 16.3% of placebo-treated patients.

Patient-reported daily worst pain was significantly improved with givosiran vs placebo in patients with AIP (p

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