Alnylam has received FDA approval for GIVLAARI^™ (givosiran) for the treatment of adults with acute hepatic porphyria (AHP). AHP is a family of ultra-rare, genetic diseases characterized by debilitating, potentially life-threatening attacks and, for some patients, chronic manifestations that negatively impact daily functioning and quality of life. Long-term complications of AHP can include chronic neuropathic pain, hypertension, chronic kidney disease and liver disease. GIVLAARI was shown to significantly reduce the rate of porphyria attacks that required hospitalizations, urgent healthcare visits or IV hemin administration at home.

 “We believe the approval of GIVLAARI represents a landmark event for the advancement of precision genetic medicines, providing new hope for patients and their caregivers living with the debilitating manifestations of AHP and unpredictable nature of AHP attacks, as well as for the doctors who diagnose and treat these patients. We are grateful to the investigators, patients and families who have helped make this new treatment option a reality for the AHP community. We also commend the FDA for recognizing the immense medical need and granting this approval so quickly,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “GIVLAARI now becomes our second RNAi therapeutic to be approved in the last 16 months, and the world’s first-ever GalNAc-conjugate RNA therapeutic to be approved, representing a watershed moment for a technology uniquely pioneered by Alnylam scientists. We believe today’s news reinforces the promise and potential of RNAi therapeutics as a whole new class of medicines and brings us one important step closer to fulfilling our Alnylam 2020 goals of building a multi-product, global commercial company with a deep clinical pipeline to drive growth and an organic product engine to fuel sustainable innovation.”

The FDA approval of GIVLAARI was received in less than four months after acceptance of the NDA, and was based on positive results from the ENVISION Phase 3 study, a randomized, double-blind, placebo-controlled, multinational study of 94 patients with AHP, at 36 study sites in 18 countries – the largest ever interventional study conducted in AHP. In ENVISION, AHP patients on GIVLAARI experienced 70% (95% CI: 60%, 80%) fewer porphyria attacks compared to placebo. GIVLAARI also resulted in a similar reduction in intravenous hemin use, as well as reductions in urinary aminolevulinic acid (ALA), and urinary porphobilinogen (PBG).

In the pivotal ENVISION study, the most common adverse reactions (reported in at least 20% of patients) with GIVLAARI were nausea (27%) and injection site reactions (25%). Other adverse reactions seen in patients treated with GIVLAARI (occurring over 5% more frequently than placebo) include rash, serum creatinine increase, transaminase elevations and fatigue. As previously reported, one patient in the GIVLAARI clinical development program experienced an anaphylactic reaction which resolved with medical management.

“Adults with AHP now have a new treatment option that has demonstrated the ability to reduce the frequency of porphyria attacks by specifically addressing factors associated with attacks and other disease manifestations of AHP,” said Manisha Balwaniⁱ, M.D., M.S, Associate Professor of the Department of Genetics and Genomic Sciences and Department of Medicine at the Icahn School of Medicine at Mount Sinai and principal investigator of the ENVISION study. “With the approval of GIVLAARI, and based on the efficacy data from the ENVISION study, I hope to see my patients and those across the country be able to live more normal lives with fewer porphyria attacks.”

“The FDA approval of GIVLAARI is an important milestone for our community, as we now have a new treatment option for adults living with acute hepatic porphyria,” said Kristen Wheeden, Executive Director, American Porphyria Foundation. “AHP can have a profound impact on the lives of patients and their families. Porphyria attacks are associated with severe, incapacitating pain, often requiring hospitalization for management. In addition, many patients struggle on a daily basis with chronic symptoms related to their disease. The approval of GIVLAARI is exciting for our community.”

Alnylam is committed to helping people access the medicines they are prescribed and will be offering comprehensive support services for people prescribed GIVLAARI through Alnylam Assist^®. Visit AlnylamAssist.com for more information or call 1-833-256-2748.

GIVLAARI is expected to be available for shipment to healthcare providers in the U.S. by year-end. HCPs can initiate the process now by visiting www.AlnylamAssist.com and completing and submitting a Start Form.

In August, Alnylam announced a U.S. gastrointestinal (GI) disease education and promotional agreement for GIVLAARI with Ironwood Pharmaceuticals, Inc., a GI healthcare company. Under the agreement, Alnylam will leverage Ironwood’s leading capabilities in GI to help raise awareness of AHP among gastroenterologists and other healthcare practitioners in the U.S. Ironwood will also participate in GIVLAARI promotional efforts, augmenting Alnylam’s broader commercialization activities.

GIVLAARI was reviewed by the FDA under Priority Review and had previously been granted Breakthrough Therapy and Orphan Drug Designations in the U.S. GIVLAARI is currently being reviewed under accelerated assessment by the European Medicines Agency (EMA) for the treatment of patients with AHP, after receiving Priority Medicines (PRIME) Designation and Orphan Drug Designation from the EMA.

Source: Alnylam (press release)

The World Health Organization (WHO) today prequalified an Ebola vaccine for the first time, a critical step that will help speed up its licensing, access and roll-out in countries most at risk of Ebola outbreaks. This is the fastest vaccine prequalification process ever conducted by WHO.

Prequalification means that the vaccine meets WHO standards for quality, safety and efficacy. United Nations agencies and Gavi, the Vaccine Alliance, can procure the vaccine for at-risk countries based on this WHO recommendation.

“This is a historic step towards ensuring the people who most need it are able to access this life-saving vaccine,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General. “Five years ago, we had no vaccine and no therapeutics for Ebola. With a prequalified vaccine and experimental therapeutics, Ebola is now preventable and treatable.”

The injectable Ebola vaccine, Ervebo, is manufactured by Merck (known as MSD outside the US and Canada). It has been shown to be effective in protecting people from the Ebola Zaire virus and is recommended by the WHO Strategic Advisory Group of Experts (SAGE) for vaccines as part of a broader set of Ebola response tools. The decision is a step towards greater availability of the vaccine in the future, though licensed doses will only be available mid-2020.

This announcement comes less than 48 hours after the European Commission decision to grant a conditional marketing authorization for the vaccine, following the recommendation from the European Medicines Agency (EMA).

Due to the urgent public health need for a prequalified Ebola vaccine, WHO accelerated prequalification by reviewing safety and efficacy data as the information became available. Representatives from the prequalification team participated in the EMA evaluation process to address programmatic suitability for at-risk countries in Africa.

“The development, study, and rapid prequalification of this vaccine show what the global community can do when we prioritize the health needs of vulnerable people,” said Dr Tedros.

WHO is also facilitating licensing of the vaccine for use in countries at risk of Ebola outbreaks, based on the reviews and positive outcome by the EMA. WHO, with the support of EMA, has worked closely with many African regulators who have indicated they will quickly license the vaccine following the WHO recommendation.

Source: WHO