Introduction
Duvelisib, marketed as COPIKTRA, is a phosphatidylinositol 3-kinase (PI3K) inhibitor used in the treatment of various hematologic malignancies. Here, we delve into the market dynamics and financial trajectory of this drug, highlighting its approvals, performance, and significant events that have shaped its commercial journey.
FDA Approvals and Indications
Duvelisib received regular approval from the FDA in September 2018 for adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior therapies. Additionally, it received accelerated approval for adult patients with relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies[1][3][5].
Clinical Trials and Efficacy
The approvals were based on several clinical trials, including the phase III DUO trial, which compared duvelisib to ofatumumab in patients with relapsed or refractory CLL or SLL. The trial showed that duvelisib significantly improved median progression-free survival (PFS) to 16.4 months compared to 9.1 months with ofatumumab, with an overall response rate (ORR) of 78% versus 39% for ofatumumab[1][3][5].
For FL, the single-arm multicenter phase 2 DYNAMO trial demonstrated an ORR of 42%, with 43% of responding patients maintaining their response for at least 6 months and 17% for at least 12 months[1][3][4].
Safety Profile
Duvelisib's prescribing information includes boxed warnings for fatal and/or serious infections, diarrhea or colitis, cutaneous reactions, and pneumonitis. Common adverse reactions include diarrhea or colitis, neutropenia, rash, fatigue, and pneumonia. Despite its efficacy, the drug's safety profile has been a significant concern, leading to permanent discontinuation in 35% of patients and dose reduction in 24%[1].
Market Performance and Financials
After its approval, duvelisib's commercial performance was modest. In 2019, the drug generated only $12 million in revenue for Verastem, Inc., the original developer and marketer. This underwhelming performance, combined with significant financial challenges faced by Verastem, including a loss of about $149 million in the same year, prompted the company to reevaluate its strategy[2].
Change in Ownership
In August 2020, Verastem sold the global commercial and development rights to duvelisib to Secura Bio, Inc. for $70 million upfront and up to $241 million in milestone payments. This deal allowed Verastem to focus on other pipeline projects, particularly its RAF/MEK/FAK development program, and reduced its annual expenses by about $50 million[2].
Withdrawal from the Market for FL Indication
In December 2021, Secura Bio voluntarily withdrew duvelisib from the U.S. market for the treatment of relapsed or refractory FL due to changes in the treatment landscape and the FDA's determination that the post-marketing requirements were no longer necessary. This decision did not impact other indications for duvelisib[4].
Current Market Position
Despite the withdrawal for the FL indication, duvelisib remains on the market for the treatment of CLL and SLL. The drug's performance and financial trajectory are closely tied to its ability to maintain market share in these indications and potentially expand into new ones, such as peripheral T-cell lymphoma, for which milestone payments are contingent[2][4].
Financial Projections and Milestones
Secura Bio is eligible for significant milestone payments, including $45 million for FDA and EMA approvals for peripheral T-cell lymphoma and $50 million for cumulative worldwide net sales starting at $100 million. Verastem will also receive low double-digit royalties on U.S., European, and UK sales, and 50% of licensing milestones up to $146 million outside these regions[2].
Conclusion
The market dynamics and financial trajectory of duvelisib are marked by initial regulatory successes, modest commercial performance, a change in ownership, and strategic adjustments in response to market and regulatory changes. As the treatment landscape for hematologic malignancies continues to evolve, the future of duvelisib will depend on its ability to demonstrate sustained clinical benefit and expand into new indications.
Key Takeaways
- Duvelisib received FDA approvals for CLL/SLL and FL but was later withdrawn from the FL market.
- The drug showed significant efficacy in clinical trials but has a challenging safety profile.
- Verastem sold duvelisib to Secura Bio to focus on other pipeline projects.
- Secura Bio is pursuing new indications and is eligible for significant milestone payments.
- The drug's financial performance has been modest, but future milestones and royalties could improve its financial outlook.
FAQs
Q: What are the approved indications for duvelisib?
A: Duvelisib is approved for adult patients with relapsed or refractory CLL or SLL after at least two prior therapies and was previously approved for FL, though this indication has been withdrawn.
Q: What were the key findings of the DUO trial?
A: The DUO trial showed that duvelisib significantly improved median PFS to 16.4 months compared to 9.1 months with ofatumumab, with an ORR of 78% versus 39% for ofatumumab.
Q: Why was duvelisib withdrawn from the market for FL?
A: Duvelisib was withdrawn from the U.S. market for FL due to changes in the treatment landscape and the FDA's determination that the post-marketing requirements were no longer necessary.
Q: Who currently owns the rights to duvelisib?
A: Secura Bio, Inc. currently owns the global commercial and development rights to duvelisib after acquiring them from Verastem, Inc. in 2020.
Q: What are the potential future milestones for duvelisib?
A: Secura Bio is eligible for milestone payments for FDA and EMA approvals for peripheral T-cell lymphoma and for achieving certain sales thresholds, as well as royalties on sales.
References
- FDA: Duvelisib (COPIKTRA, Verastem, Inc.) for adult patients with relapsed or refractory chronic lymphocytic leukemia.
- Biospace: Verastem Sells Copiktra to Secura for $311 Million to Focus on Pipeline.
- FDA: 211155Orig1s000 211155Orig2s000 - accessdata.fda.gov.
- Targeted Oncology: Duvelisib for R/R Follicular Lymphoma Voluntarily Pulled from the US Market.
- OncLive: Duvelisib Improves PFS in Phase III CLL Trial.
