Alnylam Receives FDA Nod for its Third Rare Disease Drug

Alnylam Pharmaceuticals, a Massachusetts-based leading RNAi therapeutics company, announced on November 24th the approval of OXLUMO (lumasiran), the first-ever therapy meant for lowering oxalate levels in children and adults suffering from a rare genetic disorder, Primary Hyperoxaluria type 1 (PH1). This approval comes five days after the drug got a nod from the European Commission.

Primary Hyperoxaluria type 1

PH1 is a rare condition in which mutation in a liver enzyme AGT causes accumulation of oxalate, which in turn binds with calcium to form calcium oxalate crystals in the kidneys and urinary tract. Excessive stones in the urinary tract lead to severe illness and death. So far, there are no non-surgical treatments available for these patients, and patients are forced to undergo dialysis, sometimes almost daily, to remove toxic products. Alnylam estimates that there are only 1000 to 1700 patients in the US and Europe at any particular time. Oxulmo will be able to help patients who have confirmed diagnosis but have not undergone a liver transplant.

In little more than two years, Alnylam has managed to secure FDA’s blessings for three of its RNAi interference therapies that silence genes to stop disease progression. In 2018, the company secured the USFDA approval for Onpattro, followed by the second approval for Givlaari in 2019. The Oxulma approval is important for patients, mostly kids suffering from this ultra-rare genetic condition who experience an inevitable decline in kidney function and rely on liver/kidney transplantation to address the underlying metabolic defect.

“Many people impacted by PH1 face persistent anxiety related to the unpredictable nature of their condition, in terms of the uncertainty of how quickly their disease may progress, and the prospect of needing intensive dialysis and a kidney/liver transplant that threaten their physical, emotional and financial health,” said Kim Hollander, Executive Director of the Oxalosis and Hyperoxaluria Foundation. “The FDA approval of OXLUMO represents a new path forward for many, providing an effective treatment option and a sense of hope.”

ILLUMINATE-A and B trials

Oxlumo works by snapping a messenger RNA to prevent the production of a tissue-damaging chemical called oxalate. FDA’s approval of the drug is primarily based on the ILLUMINATE-A study, but the FDA also considered positive results from the pediatric study that included children under the age of 6. In ILLUMINATE-A, the largest controlled Phase 3 study ever conducted, Oxlumo successfully reduced the levels of urinary oxalate in PH1 adult patients to almost that of healthy individuals. Topping that, the drug showed encouraging safety and tolerability profile in these patients. In a parallel study, ILLUMINATE-B, which included children under six, Oxlumo successfully reduced oxalate levels with minimal adverse events.

Priceless Drug but with a Hefty Price Tag

While it is good news for the patients, the drug will come at a hefty cost. Alnylam is pricing the medicine at $493,000 per patient per year on average, and it expects the net price will come in at about $380,000 per patient per year. But to make it easy for the patients, Alnylam is working with payers to set up “value-based agreements” for the sale of Oxlumo. This means that the drug’s price will be defined by how the drug performs in real-world scenarios instead of data and evidence collected during highly controlled trials. This will ensure payers efficient pricing mechanisms and reduce their risk of purchasing a suboptimal drug. Alnylam has concluded initial talks with Express Scripts, Harvard Pilgrim, and Highmark to pursue the agreements.

So far, Alnylam’s PH1 medication is the only one ruling the market, but this isn’t expected to last forever. Dicerna is also coming up with its RNAi medication that will cover the range of PH diseases including, PH1, PH2, and PH3. While Dicerna is far away from getting into the market, whenever it comes, it will be a big competitor for Alnylam.

Akshay Vaishnaw, M.D., Ph.D., President of R&D at Alnylam rejoiced at the approval and said, “OXLUMO marks our third FDA approval in less than three years, positioning us to meet or exceed our Alnylam 2020 strategy and goals and further highlighting the productivity of our RNAi platform and the speed at which we can bring innovative medicines to patients. For patients and families impacted by PH1, this is a historic moment, as OXLUMO represents the first, targeted therapeutic option available to them. We are grateful to all the investigators, staff, and patients who participated in the ILLUMINATE clinical studies and to their families, caregivers, and patient advocates. This moment is what we all had hoped for.”

By Ruchi Jhonsa, Ph.D.

Related Article: Alnylam’s RNAi-Based Therapy Lumasiran Impresses in Phase 3 Primary Hyperoxaluria Trials

References

1. https://investors.alnylam.com/press-release?id=25271

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Author

Ruchi Jhonsa