Rusfertide still needs to be Verified
An FDA verdict is due in the third quarter, as Protagonist looks likely to opt out.
An FDA verdict is due in the third quarter, as Protagonist looks likely to opt out.
The FDA has accepted a filing for Takeda and Protagonist’s rusfertide for treating polycythemia vera, with a PDUFA date in the third quarter, but a bigger decision, on Protagonist's future involvement in this project, is looming.
Protagonist, rusfertide's originator, is planning to opt out of a 50/50 profit share under its 2024 deal with Takeda, it said in its fourth-quarter release last week. If this path is pursued it could again raise questions about the addressable market size for this project.
Protagonist says it expects to exercise the opt-out right in the second quarter, a move that would allow it to collect $400m, on top of the $300m that Takeda initially paid. Protagonist would also be eligible for 14-29% royalties (versus 10-17% if it remained opted in), and could receive up to $975m in milestones (versus up to $330m).
Low peak?
Current therapy for polycythemia vera, which involves overproduction of red blood cells and is thought to affect around 100,000 US patients, includes phlebotomy (blood removal) and cytoreductive agents like hydroxyurea, interferon and Novartis/Incyte’s Jakafi.
Protagonist estimated in January that rusfertide could generate peak sales of $1-2bn, so taking the money now looks like a sensible decision. One question is why Takeda allowed the deal to be structured in this way; another is why a rival player, Ono, last year spent $280m up front licensing another polycythemia vera hopeful, Ionis’s sapablursen.
This all assumes that rusfertide, a hepcidin mimetic, will gain the FDA nod, although this looks likely based on the phase 3 Verify study, which found a 77% response rate in the rusfertide arm versus 33% with control, and also met secondary endpoints, including a reduction in phlebotomy rates.
Cancer concerns were previously raised, including animal data that led to a clinical hold, although Verify appears to have avoided these worries. The most common adverse events in rusfertide-treated patients were injection-site reactions (47%), anaemia (26%) and fatigue (20%), mainly at grade 1 or 2. Serious adverse events occurred in 8% of rusfertide-treated patients.
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