Introduction to CALQUENCE
CALQUENCE, developed by AstraZeneca, is a next-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK) known as acalabrutinib. It has been approved for the treatment of various B-cell blood cancers, including chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL)[5].
Clinical Trials Update
ECHO Trial in Mantle Cell Lymphoma (MCL)
A significant milestone for CALQUENCE was achieved in the ECHO phase 3 trial, where it demonstrated a statistically significant improvement in progression-free survival (PFS) when used in combination with bendamustine and rituximab (BR) in newly diagnosed MCL patients. This trial, which concluded earlier than expected, showed that the CALQUENCE combination significantly delayed cancer progression or death compared to the standard chemoimmunotherapy alone. Although the overall survival (OS) data were not yet mature, a positive trend in favor of CALQUENCE was observed[1][5].
AMPLIFY Trial in Chronic Lymphocytic Leukemia (CLL)
In the AMPLIFY phase 3 trial, CALQUENCE was evaluated in a fixed-duration regimen in combination with the BCL-2 inhibitor Venclexta (venetoclax) with or without the anti-CD20 antibody Gazyva (obinutuzumab) in first-line CLL. The trial showed that CALQUENCE plus Venclexta reduced the risk of disease progression or death by 35%, and the triplet regimen of CALQUENCE, Venclexta, and Gazyva achieved a 58% reduction compared to standard chemoimmunotherapy. However, the OS data were still immature at the time of analysis[4].
Escalade Trial in Diffuse Large B-Cell Lymphoma (DLBCL)
The Escalade phase 3 trial is ongoing, evaluating CALQUENCE in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in first-line DLBCL. The results of this trial are expected to be crucial for expanding CALQUENCE's indications[4].
Other Ongoing Trials
AstraZeneca is conducting over 20 company-sponsored clinical trials for CALQUENCE, targeting various B-cell blood cancers including DLBCL, CLL, MCL, Waldenström's macroglobulinemia, follicular lymphoma, and marginal zone lymphoma. These trials are part of an extensive clinical development program aimed at solidifying CALQUENCE's position in the market[3].
Market Analysis
Current Market Performance
CALQUENCE has been performing well in the market, with sales increasing by 22% in 2023 to $2.5 billion. In the first nine months of 2024, revenues from CALQUENCE rose by 26% to $2.3 billion. This growth is attributed to its strong efficacy and safety profile, particularly in the first-line CLL setting where it remains the leading BTK inhibitor in the U.S. and Europe[1][4].
Competitive Landscape
The BTK inhibitor market is highly competitive, with CALQUENCE facing competition from BeiGene's Brukinsa. Brukinsa has shown promising results, especially in the CLL setting, and is being evaluated in several ongoing trials. The rivalry between CALQUENCE and Brukinsa is expected to intensify, especially with the emergence of new treatments such as degraders from BeiGene and Nurix[1][4].
Sales Projections
Given its strong clinical trial data and expanding indications, CALQUENCE is projected to continue its growth trajectory. The success in the ECHO trial and the potential approval in first-line MCL early next year are expected to further boost its market position. However, the impact of fixed-duration therapy and the competition from other BTK inhibitors will be key factors to watch in the future[4].
Patent and Exclusivity
Patent Expiration
The patents protecting CALQUENCE are set to expire on July 1, 2036, although this date could change due to patent challenges or generic licensing. There have been several patent litigation cases, indicating strong interest in generic entry once the exclusivity period ends[2].
Regulatory Protections
CALQUENCE has multiple regulatory protections, including nine patents in the U.S. and 183 patent family members in 49 countries. These protections are crucial for maintaining its market exclusivity until the estimated generic entry date[2].
Safety and Tolerability
Differentiated Safety Profile
CALQUENCE has been highlighted for its differentiated safety profile. In the ECHO trial, the safety and tolerability of CALQUENCE were consistent with its known safety profile, with no new safety signals identified. This safety profile is a significant advantage, especially when compared to other BTK inhibitors like Imbruvica, which faced issues related to its safety profile[1][5].
Expert Insights
Michael Wang, MD, Principal Investigator in the ECHO trial, noted that the positive PFS results from the ECHO trial could provide a new standard of care for patients with MCL, offering robust efficacy and a strong safety profile[5].
Susan Galbraith, Ph.D., Executive Vice President, Oncology R&D at AstraZeneca, emphasized that the results in MCL show that bringing CALQUENCE to the first-line setting significantly delays disease progression and potentially extends survival, highlighting its differentiated safety profile[5].
Key Takeaways
- Clinical Success: CALQUENCE has shown significant clinical success in the ECHO trial for MCL and the AMPLIFY trial for CLL.
- Market Performance: CALQUENCE continues to grow in sales, driven by its strong efficacy and safety profile.
- Competitive Landscape: The drug faces competition from Brukinsa but remains a leader in the BTK inhibitor market.
- Patent and Exclusivity: CALQUENCE's patents are set to expire in 2036, but it enjoys multiple regulatory protections.
- Safety Profile: CALQUENCE is known for its differentiated and favorable safety profile.
FAQs
What is CALQUENCE used for?
CALQUENCE (acalabrutinib) is used for the treatment of various B-cell blood cancers, including CLL, SLL, and MCL.
What were the key findings of the ECHO trial?
The ECHO trial showed that CALQUENCE in combination with bendamustine and rituximab significantly improved PFS in newly diagnosed MCL patients and showed a positive trend in overall survival.
How does CALQUENCE compare to other BTK inhibitors?
CALQUENCE has a differentiated safety profile compared to other BTK inhibitors like Imbruvica and faces competition from BeiGene's Brukinsa, but it remains a leading BTK inhibitor in the market.
When are the patents for CALQUENCE set to expire?
The patents for CALQUENCE are set to expire on July 1, 2036, although this date could change due to patent challenges or generic licensing.
What is the current market performance of CALQUENCE?
CALQUENCE has seen significant sales growth, with revenues increasing by 22% in 2023 and 26% in the first nine months of 2024.
Sources
- Fierce Pharma: "AZ clinches early Calquence win in untreated MCL - Fierce Pharma"
- DrugPatentWatch: "When will the patents on CALQUENCE expire ... - DrugPatentWatch"
- ResearchAndMarkets: "CALQUENCE Emerging Drug Insight and Market Forecast - 2032"
- ApexOnco: "ASH 2024 – AstraZeneca aims to fix Calquence's position | ApexOnco"
- AstraZeneca: "Calquence combination regimen demonstrated statistically ... - AstraZeneca"
