The U.S. Food and Drug Administration (FDA) approved Alnylam Pharmaceuticals’ Givlaari (givosiran) for acute hepatic porphyria (AHP). AHP is a group of ultra-rare, genetic diseases, which causes severe abdominal pain and potentially life-threatening attacks.
Givlaari is based on RNA interference (RNAi), which is a technique used to silence abnormal gene expression. Givlaari is only the second drug to be approved leveraging RNAi. The first was also an Alnylam product, Onpattro (patisiran), which launched in August 2018 for polyneuropathy in hATTR amyloidosis.
Long-term complications of AHP include chronic neuropathic pain, hypertension, chronic kidney disease and liver disease. Givlaari has demonstrated the ability to significantly decrease the rate of porphyria attacks requiring hospitalizations, urgent healthcare or IV hemin administration.
“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,” said John Marganore, chief executive officer of Alnylam. “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.”
Givlaari is expected to cost $575,000 annually. After discounts, the average price is projected to be $442,000 per year, with a vial of the drug running $39,000. This is similar to the pricing for Onpattro, which runs up to $450,000, but payers have worked out deals that link the cost to how well patients respond to it. This is likely to be a similar strategy for Givlaari.
Marganore told STAT that Givlaari will also come with a prevalence-based adjustment. In other words, if a payer finds itself with a higher-than-expected number of patients with the condition, Alnylam will pay the insurer a rebate.
“That’s never been done before in the rare disease space, but it’s something we think is a responsible and appropriate way to think about ultra-rare, orphan drug pricing,” Maraganore told STAT. “We don’t really know what the prevalence is of the disease. If our current estimates are correct, we’ll expect to get the price that we’re asking for. If, on the other hand, as we improve education, improve disease awareness, if the prevalence goes up a lot, we’re willing to take the price down, effectively. Which is almost never done.”
In one of the company’s clinical trials for the drug, about half of the patients receiving Givlaari had complete elimination of the acute hepatic porphyria attacks. However, on average, patients demonstrated a 74% decrease in these attacks in more than six months.
“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 Balwani, associate professor of the Department of Genetics and Genomic Sciences and Department of Medicine at the Icahn School of Medicine at Mount Sinai. Balwani is also the principle 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 to be able to live more normal lives with fewer porphyria attacks.”-Bio Space