Brain cancers are notoriously difficult to treat, with surgery and radiation continuing to be the main options for these malignancies. A rare and aggressive type of brain tumor driven by a particular genetic signature could soon have its first approved drug treatment. Jazz Pharmaceuticals is now committing $935 million to add this prospect to its pipeline.
The drug, dordaviprone, was developed by Durham, North Carolina-based Chimerix. The cancer is H3 K27M-mutant diffuse glioma, a high-grade glioma that affects children and young adults. While surgery is a treatment option for brain cancers, it’s usually risky for H3 K27M gliomas because these tumors affect critical parts of the brain and spinal cord. Meanwhile, radiation introduces complication risks and is not curative.
“This is a very high unmet need,” Jazz Chief Medical Officer Robert Iannone said, speaking during the company’s presentation Wednesday at TD Cowen’s annual health care conference in Boston. “I’m a pediatric oncologist by training. There really has been no progress in this area. I know from treating these patients, it’s been a very sad situation to have only radiation and surgery as the effective therapy.”
About 2,000 patients are affected by H3 K27M-mutant gliomas annually in the U.S., according to a Chimerix estimate. Dordaviprone is part of a new class of cancer drugs called imipridones. These small molecules target certain G protein-coupled receptors and enzyme targets, altering their activity to lead to cancer cell death. Dordaviprone, known earlier in its development as ONC201, is designed to selectively target mitochondrial protease ClpP and dopamine receptor D2.
Phase 2 results showed tumor regression in patients with glioblastoma who exhibited the H3 K27M mutation. In the 50 patients included in the primary efficacy analysis, Chimerix reported a 28% objective response rate and a median duration of response of 10.4 months. A Phase 3 test enrolling patients newly diagnosed with this type of brain cancer could support first-line use of the drug; interim results are expected in the third quarter of 2025. But based on the Phase 2 data, Chimerix is seeking accelerated approval of dordaviprone for recurrent H3 K27M-mutant diffuse glioma. Last month, the FDA accepted the new drug application under priority review, setting an Aug. 18 target date for a regulatory decision.
Though cancer is the therapeutic focus of Chimerix, it’s a relatively new area for the company, one of the older biotechs in North Carolina’s Research Triangle. Dordaviprone came from Chimerix’s 2021 cash and stock acquisition of Oncoceutics, a clinical-stage developer of imipridones. Besides the lead drug candidate, the deal also brought ONC206, an imipridone that Chimerix has advanced to Phase 1 testing in central nervous system tumors. Per terms of the Oncoceutics acquisition, that company’s shareholders could receive up to $360 million in milestone payments plus royalties from sales.
Chimerix, founded in 2000, began as an antiviral drug developer. For most of the biotech’s history, its focus was brincidofovir, a molecule initially developed for treating cytomegalovirus infection. It failed in that indication, but won FDA approval in 2021 as a treatment for smallpox and is now known by the brand name Tembexa. In 2022, Chimerix sold that drug’s rights to Emergent BioSolutions for $225 million up front and up to $100 million in milestone payments. Chimerix applied the cash toward clinical development of dordaviprone in brain cancer.
In the past year, Chimerix’s stock price has mostly traded below the $1 mark. Those shares got a significant lift in December after the biotech announced it would seek accelerated approval for dordaviprone. According to acquisition terms disclosed Wednesday, Dublin-based Jazz will pay $8.55 in cash for each Chimerix share, representing a 72% premium to the biotech’s closing stock price on Tuesday. There’s potential for additional financial upside. Because Chimerix’s drug is under priority review, it’s eligible for a rare pediatric disease priority review voucher if the drug is approved. Such vouchers are typically sold to big pharma companies, and they once fetched prices in the range of $100 million. Recent voucher sales have been in the neighborhood of $150 million.
The Jazz portfolio currently has five cancer drugs. Chief Financial Officer Philip Johnson described dordaviprone as a “great fit with our oncology business,” adding that the drug can leverage Jazz’s commercial capabilities and offers a patent life extending into 2037 and potentially longer.
The Chimerix acquisition fits Jazz’s strategy of acquiring assets for rare opportunities in niche markets, Leerink Partners analyst Marc Goodman wrote in a note to investors. Beyond addressing a high unmet medical need, the deal leverages Jazz’s expertise in rare diseases and oncology. Jazz prefers acquiring late-stage assets that have a potential near-term commercial launch, Goodman said. Leerink is still researching the H3 K27M market opportunity, but he noted that given the size of the patient population for this ultra-rare type of cancer, it makes sense for dordaviprone to fall within the $300,000 to $800,000 price range for orphan drug products.
The acquisition has been approved by the boards of both Jazz and Chimerix, but still must meet customary closing conditions including the tender of the majority of the outstanding shares of Chimerix. The companies expect the deal to close in the second quarter of this year.
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