Givosiran (also known as ALN-AS1) is an RNA-based therapy that works by blocking the activity of the enzyme aminolevulinic acid synthase 1 (ALAS1), whose loss stops the accumulation of toxic compounds that cause AHP.
The treatment is under priority review for possible approval by the United States Food and Drug Administration, the agency announced this month. Its application was supported by data from the Phase 3 ENVISION trial (NCT03338816), which found that givosiran decreased by 74% the annual rate of porphyria attacks compared to placebo, and lowered urine levels of aminolevulinic acid (a key biomarker of AHP) in treated patients by 92%.
Givosiran has also been given breakthrough therapy and orphan drug designations by the FDA, and their equivalents by the European Medicines Agency, which is also reviewing an approval request.
An FDA decision is expected on or before Feb. 4, 2020.
Under the terms of the agreement, Ironwood will provide education about AHP to healthcare practitioners — particularly gastroenterologists, doctors who specialize in the intestinal system — similar to what the company currently provides for Linzess (linaclotide), a medication for constipation and irritable bowel syndrome.
If givosiran is approved, clinical sales specialists working for Ironwood will also help to promote its sales.
“We are excited about the opportunity to partner with Alnylam to increase awareness among healthcare providers about the devastating effects of AHP and, if approved, to then discuss givosiran as a potential new treatment option for patients suffering from this severe, potentially life-threatening disease,” Tom McCourt, the president of Ironwood, said in a press release.
In return for these educational and sales efforts, Ironwood will receive fixed payments (amount not disclosed) as well as royalties “in the mid-teens percent” for referrals and prescriptions by physicians who are on the receiving end of Ironwood’s efforts. Alnylam will maintain responsibility for all other aspects of givosiran, including development and commercialization.
The agreement covers a time period of about three years and is non-exclusive.
“Nearly all patients living with AHP consult at least one, if not several, gastroenterologists due to the recurring abdominal pain associated with their disease and are often misdiagnosed due to minimal disease awareness and a limited number of treatment options,” said Barry Greene, the president of Alnylam.
“As Alnylam prepares for the potential launch and commercialization of givosiran around the world, leveraging Ironwood’s U.S. GI commercial expertise and depth of relationships within the GI community represents a significant opportunity to expand medical education and diagnosis for patients with AHP,” he added.