Last updated: January 7, 2025
Introduction
Copanlisib dihydrochloride, marketed as Aliqopa, is a small molecule drug that inhibits the phosphatidylinositol 3-kinase (PI3K) alpha and delta isoforms. It was initially approved by the FDA in September 2017 for the treatment of adult patients with relapsed follicular lymphoma who have received at least two prior systemic therapies. Here, we will delve into the recent clinical trials updates, market analysis, and projections for this drug.
Clinical Trials Update
Accelerated Approval and Phase 2 CHRONOS-1 Study
Copanlisib received accelerated approval based on the results of the phase 2 CHRONOS-1 study (NCT01660451). This study demonstrated an objective response rate (ORR) of 58.7% in patients with relapsed follicular lymphoma, including a complete response (CR) rate of 14.4% and a partial response rate of 44.2%. The median duration of response (DOR) was 12.2 months[1][5].
Phase 3 CHRONOS-4 Study
The FDA required a phase 3 trial, CHRONOS-4 (NCT02626455), to confirm the clinical benefit of copanlisib. However, this trial did not meet its primary endpoint of improving progression-free survival (PFS) when copanlisib was combined with chemoimmunotherapy regimens compared to standard chemoimmunotherapy alone. This led to Bayer's decision to voluntarily withdraw the new drug application for copanlisib in this indication[1].
Ongoing and Completed Trials
Several other clinical trials involving copanlisib are either completed or ongoing. For example, a phase 2 trial evaluating copanlisib plus avelumab as maintenance therapy for metastatic bladder cancer after platinum-based chemotherapy has shown promising results. Additionally, studies combining copanlisib with other agents like abemaciclib and fulvestrant are in various phases of clinical development[4].
Market Analysis
Budget Impact Analysis
A budget impact analysis conducted from the perspective of a U.S. third-party payer found that adding copanlisib to a formulary resulted in a small increase in total budget. Over a 1-year period, the addition of copanlisib increased the total budget by $242,641, which translates to $0.02 per member per month. This increase was considered affordable, especially when balanced against the concurrent increase in the use of other therapies like obinutuzumab plus bendamustine and lenalidomide plus rituximab[2].
Market Positioning
Despite the withdrawal of the indication for relapsed follicular lymphoma, copanlisib remains an option for patients who have experienced a favorable response and for whom there are no suitable alternative treatments. Bayer is exploring access options for these patients, indicating a continued, albeit limited, market presence[1].
Competitive Landscape
The market for treatments of relapsed follicular lymphoma is competitive, with several other therapies available, including obinutuzumab, lenalidomide, and rituximab-based regimens. The failure of copanlisib to meet its primary endpoint in the CHRONOS-4 trial has impacted its market positioning, making it less competitive compared to other approved treatments[1][2].
Projections
Future Clinical Development
Given the mixed results from clinical trials, the future development of copanlisib will likely focus on other indications and combination therapies. Ongoing trials in metastatic bladder cancer and other solid tumors may offer new avenues for approval and market expansion[4].
Regulatory Considerations
The regulatory landscape for copanlisib is complex, with accelerated approval in the U.S. and various designations such as Fast Track, Orphan Drug, and Priority Review in different regions. Future approvals will depend on the outcomes of ongoing and planned clinical trials[4].
Patient Access
Bayer's commitment to maintaining access for patients who have benefited from copanlisib is crucial. This strategy ensures that patients who are currently receiving the drug and experiencing positive outcomes can continue their treatment, albeit under specific conditions[1].
Key Takeaways
- Clinical Trials: Copanlisib's phase 3 CHRONOS-4 trial did not meet its primary endpoint, leading to the withdrawal of its indication for relapsed follicular lymphoma.
- Market Analysis: The addition of copanlisib to a formulary results in a small budget increase, making it an affordable option for payers.
- Market Positioning: Despite the withdrawal, copanlisib remains an option for patients with favorable responses and no suitable alternatives.
- Future Development: Ongoing trials in other indications and combination therapies may offer new market opportunities.
FAQs
What is copanlisib dihydrochloride used for?
Copanlisib dihydrochloride, marketed as Aliqopa, is used to treat adult patients with certain types of non-Hodgkin lymphoma, although its indication for relapsed follicular lymphoma has been withdrawn in the U.S.[1][5].
What were the results of the CHRONOS-4 trial?
The CHRONOS-4 trial did not show that copanlisib significantly improved progression-free survival when combined with chemoimmunotherapy regimens compared to standard chemoimmunotherapy alone[1].
How does copanlisib affect the budget of healthcare payers?
Adding copanlisib to a formulary results in a small increase in the total budget, approximately $0.02 per member per month, which is considered affordable[2].
What are the future prospects for copanlisib?
Future development will likely focus on other indications and combination therapies, with ongoing trials in metastatic bladder cancer and other solid tumors[4].
Can patients still receive copanlisib if they have benefited from it?
Yes, Bayer is exploring access options for patients who have experienced a favorable response to copanlisib and for whom there are no suitable alternative treatments[1].
Sources
- Bayer Withdraws US Indication for Copanlisib in Relapsed Follicular Lymphoma. Onclive.
- A Budget Impact Analysis of the Introduction of Copanlisib. PubMed.
- Relapsed or Refractory Indolent Non-Hodgkin Lymphoma | Study 21960. Clinical Trials Bayer.
- Copanlisib dihydrochloride - Drug Targets, Indications, Patents. Synapse Patsnap.
- 209936Orig1s000 - accessdata.fda.gov. FDA.
