Delving into duvelisib

Infinity, AbbVie link up to develop Infinity’s PI3K-delta/gamma inhibitor in oncology

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CAMBRIDGE, Mass.—The phosphoinositide-3-kinase (PI3K) family of enzymes is involved in a number of cellular functions, such as cell proliferation, survival, differentiation, migration and immunity, and as such, they’re an attractive target for cancer therapeutics. Attractive enough, in fact, that Boston-area Infinity Pharmaceuticals Inc. and Chicago-area AbbVie Inc. are looking to explore that potential with a new collaboration.
The companies will be collaborating on the development and commercialization of IPI-145, or duvelisib, an oral inhibitor of PI3K-delta and PI3K-gamma, for the treatment of patients with cancer. Given that the compound has demonstrated clinical activity in a number of blood cancers, Infinity is advancing duvelisib in that area, conducting registration-focused trials to evaluate the safety and efficacy of duvelisib in DYNAMO, a Phase 2 study in patients with indolent non-Hodgkin lymphoma (iNHL), and DUO, a Phase 3 study in patients with chronic lymphocytic leukemia.
“We believe that duvelisib is a very promising investigational treatment based on clinical data showing activity in a broad range of blood cancers,” Dr. Michael Severino, AbbVie’s executive vice president and chief scientific officer, commented in a statement. “The addition of duvelisib will complement AbbVie’s emerging oncology pipeline and expand our research into combination therapies to generate improved outcomes for cancer patients. We look forward to working with Infinity to bring duvelisib to patients worldwide.”
Per the terms of the agreement, AbbVie will pay Infinity $275 million up front, and the latter will be eligible to receive up to an additional $530 million if all development, regulatory and commercial milestones are met, including up to $405 million for the achievement of milestones through the first commercial sale of duvelisib. The companies will jointly commercialize the drug and share profits equally in the United States, and outside of the country, AbbVie will be responsible for the conduct and funding of duvelisib’s commercialization, with Infinity eligible to receive tiered double-digit royalties on net product sales. AbbVie and Infinity have established a global development plan for the conduct of a number of trials. To begin with, Infinity will be responsible for funding the trials it conducts, while the companies will share the cost of funding the trials AbbVie conducts.
“This collaboration is an important step toward fulfilling Infinity’s objective of bringing better treatments to patients and further advances our goal of building a sustainable, fully integrated biotechnology company,” Adelene Q. Perkins, Infinity’s chair, president and CEO, said in a news release. “AbbVie will be a wonderful partner for Infinity, bringing all of the expertise and scale of a successful, well-established company, together with the energy, drive, innovation and nimbleness of a young organization. We look forward to advancing duvelisib through monotherapy studies designed to enable registration and in furthering our shared longer-term vision of combining duvelisib with both current standards of care and novel, targeted therapies.”
This is the first time the companies have worked together, says Perkins, who notes that Infinity and AbbVie “had tremendous alignment on the vision we had on the program.”
“The development of PI3kinase inhibitors has garnered a lot of attention over the last few years, and there are four different isoforms: alpha, beta, delta and gamma,” Perkins explains. “There are some molecules that are being developed as pan-inhibitors of all four isoforms; those tend to be in solid tumors. There’s been a great deal of research to show the value of delta, and Infinity’s really pushing the field to understand the role of gamma inhibition in hematologic malignancies. Both delta and gamma play an important role in the trafficking of certain cells that are required and certain signaling pathways that are required for cancer cells to survive and proliferate.”
The PI3K-delta and PI3K-gamma isoforms are preferentially expressed in leukocytes (white blood cells), where they hold distinct roles in immune cell development and function. Infinity believes the inhibition of the two isoforms is actually synergistic, Perkins adds, citing the promising data seen in their Phase 1 trials in iNHL: 73 percent of patients receiving duvelisib saw a reduction in tumor burden, and over 20 percent of those patients saw a complete response, something Perkins calls “very striking” for a monotherapy.
Analyst outlooks on the compound’s prospects are a bit more reserved. Adam Feuerstein of TheStreet noted that duvelisib is up against two already-approved drugs for market space: Zydelig (which is also a PI3K inhibitor) from Gilead Sciences and Imbruvica from Pharmacyclics. There have also been concerns about its safety and tolerability when compared to competitors in the PI3K inhibitor class. Despite reservations as to whether the drug candidate is worth the potential $805-million price tag, however, Zacks Equity Research is optimistic about the deal, calling duvelisib “a great strategic fit for AbbVie’s existing pipeline” and adding that “with AbbVie’s expertise, the candidate may hit the market faster.”

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