Takeda and Protagonist's Blood Cancer Drug Succeeds in Phase 3 Trial

Takeda Pharmaceutical and Protagonist Therapeutics have announced positive results from their Phase 3 VERIFY trial of rusfertide, a novel injectable drug for the treatment of polycythemia vera (PV), a rare blood cancer. The success of this late-stage study marks a significant milestone for both companies and potentially offers a new treatment option for patients with this challenging condition.

Rusfertide Demonstrates Efficacy in Reducing Phlebotomy Need

The VERIFY trial, which enrolled nearly 300 patients with uncontrolled polycythemia vera, met its primary endpoint with impressive results. According to the data released by the companies, 77% of participants receiving rusfertide achieved a clinical response, defined as not requiring phlebotomy during weeks 20 to 32 of treatment. This was in stark contrast to the placebo group, where only 33% of patients met the same criteria.

Dinesh Patel, CEO of Protagonist Therapeutics, expressed enthusiasm about the results, stating, "The totality of impressive clinical data to date shows that rusfertide has the potential for meaningful positive impact on the lives of patients with PV." He added that these results "mark a critical inflection point in Protagonist's decade-long journey in the hepcidin program."

Mechanism of Action and Secondary Endpoints

Rusfertide, an investigational injectable hepcidin mimetic, is designed to address the excessive production of red blood cells characteristic of PV. This overproduction can lead to increased risks of life-threatening cardiovascular and thrombotic events, necessitating regular phlebotomy procedures to manage hematocrit levels.

The trial also met its secondary endpoints, demonstrating improved hematocrit control and a relative reduction in fatigue among treated patients. These outcomes suggest that rusfertide may offer comprehensive benefits beyond reducing the need for phlebotomy.

Partnership and Financial Implications

The success of the VERIFY trial represents a significant win for Takeda, which invested $300 million in January 2024 to license rusfertide from Protagonist. Under the terms of their agreement, Takeda holds exclusive rights for development and commercialization activities outside the United States, while the companies will share a 50/50 profit split for U.S. commercialization.

This positive outcome triggers a $25 million milestone payment from Takeda to Protagonist, as stipulated in their licensing agreement. The partnership aligns with Takeda's strategy to acquire late-stage assets in the rare disease space, as highlighted by Andy Plump, Takeda's president of R&D, who stated, "We are deeply committed to bringing additional treatment options to those living with blood cancers, including myeloid cancers such as PV."

Regulatory Outlook and Market Potential

With these encouraging results in hand, Protagonist and Takeda are preparing to submit their findings to regulatory agencies. The companies plan to present detailed data at an upcoming medical meeting, which will likely provide further insights into rusfertide's efficacy and safety profile.

It's estimated that 100,000 to 160,000 people in the United States have polycythemia vera. Given the limited treatment options currently available for PV, rusfertide could potentially address a significant unmet medical need in this patient population.

As the pharmaceutical industry closely watches the progress of this promising therapy, the success of rusfertide not only represents a potential breakthrough for patients with PV but also validates Protagonist's peptide-based drug development platform and Takeda's strategic investment in rare disease treatments.