Introduction to Glasdegib
Glasdegib, marketed under the brand name Daurismo, is a small-molecule Hedgehog inhibitor developed by Pfizer. It is used in the treatment of acute myeloid leukemia (AML), particularly in patients who are not candidates for intensive chemotherapy due to age or comorbidities.
Clinical Trials Update
BRIGHT AML 1003 Trial
The FDA approval of glasdegib was based on the results of the BRIGHT AML 1003 trial, a randomized study that compared glasdegib in combination with low-dose cytarabine (LDAC) to LDAC alone in newly diagnosed AML patients aged 75 years or older, or those with comorbidities that precluded intensive chemotherapy. This trial demonstrated significant clinical benefit, with a median overall survival (OS) of 8.3 months for the glasdegib + LDAC group compared to 4.3 months for the LDAC alone group. The hazard ratio (HR) for OS was 0.46, indicating a significant improvement in survival with the addition of glasdegib[2].
BRIGHT AML 1019 Trial
The BRIGHT AML 1019 trial, a phase 3 randomized study, evaluated the efficacy and safety of glasdegib in combination with either intensive chemotherapy (cytarabine and daunorubicin) or non-intensive chemotherapy (azacitidine) in patients with untreated AML. Unfortunately, this trial did not meet its primary endpoint, as the addition of glasdegib did not significantly improve overall survival in either the intensive or non-intensive chemotherapy groups. The trial, however, confirmed the acceptable safety profile of glasdegib without revealing new safety concerns[1][4].
Safety and Efficacy Profile
Safety
Both the BRIGHT AML 1003 and 1019 trials highlighted that glasdegib has an acceptable safety profile. The most common treatment-emergent adverse events in the BRIGHT AML 1019 trial included nausea, febrile neutropenia, and anemia in the intensive study, and anemia, constipation, and nausea in the non-intensive study. The proportion of patients experiencing adverse events was similar between the glasdegib and placebo arms[1][4].
Efficacy
While the BRIGHT AML 1003 trial showed promising results with improved overall survival and complete response rates when glasdegib was combined with LDAC, the BRIGHT AML 1019 trial did not replicate these findings in the context of intensive or non-intensive chemotherapy. This discrepancy suggests that the efficacy of glasdegib may be highly dependent on the specific chemotherapy regimen and patient population[2][4].
Market Analysis
Current Market
The Hedgehog pathway inhibitors market, which includes glasdegib, was valued at USD 1.32 billion in 2023. This market is expected to grow at a compound annual growth rate (CAGR) of 16.63%, reaching USD 3.89 billion by 2030. This growth is driven by increasing demand for targeted therapies in oncology and the expanding use of Hedgehog pathway inhibitors in various malignancies[5].
Competitive Landscape
Glasdegib is part of a competitive market that includes other Hedgehog pathway inhibitors. Key players in this market include Pfizer, Eli Lilly and Company, F. Hoffmann La Roche Ltd., and Novartis AG, among others. The competitive landscape is dynamic, with ongoing research and development aimed at improving treatment outcomes and expanding the use of these inhibitors into new indications[5].
Cost-Effectiveness and Pharmacoeconomic Analysis
Incremental Cost-Effectiveness Ratio (ICER)
The pharmacoeconomic analysis of glasdegib in combination with LDAC versus LDAC alone has shown varying results. In the CADTH report, the ICER for glasdegib + LDAC ranged from $155,645 to $367,933 per quality-adjusted life year (QALY) gained, depending on the patient population and cytogenetic risk. However, these analyses often highlight the uncertainty and challenges in determining the cost-effectiveness of glasdegib due to limitations in data and health state utilities[3].
Budget Impact
The introduction of glasdegib to the market is estimated to have a significant budget impact. According to the CADTH report, the total incremental cost over the first three years for the main population is estimated to be around $21.5 million, based on revised market shares and uptake rates[3].
Projections and Future Outlook
Market Growth
The Hedgehog pathway inhibitors market is projected to continue growing, driven by the increasing incidence of hematologic malignancies and the need for more effective and targeted therapies. Glasdegib, as a part of this market, is expected to benefit from this growth, although its specific market share will depend on its performance in various clinical settings and patient populations[5].
Research and Development
Ongoing and future clinical trials will be crucial in defining the optimal use of glasdegib and other Hedgehog pathway inhibitors. Research into combination therapies and the exploration of new indications could further expand the market for these drugs. Additionally, advancements in understanding the Hedgehog signaling pathway and its role in cancer will continue to drive innovation in this field[2][5].
Key Takeaways
- Clinical Efficacy: Glasdegib has shown significant clinical benefit when combined with LDAC in elderly or comorbid AML patients but did not improve overall survival when added to intensive or non-intensive chemotherapy.
- Safety Profile: Glasdegib has an acceptable safety profile with common adverse events similar to those seen with chemotherapy alone.
- Market Analysis: The Hedgehog pathway inhibitors market is growing, with glasdegib being a key player, although its cost-effectiveness varies by patient population.
- Future Outlook: Continued research and development are expected to expand the use of glasdegib and other Hedgehog pathway inhibitors, driving market growth.
FAQs
What is glasdegib and how is it used?
Glasdegib is a small-molecule Hedgehog inhibitor used in the treatment of acute myeloid leukemia (AML), particularly in patients who are not candidates for intensive chemotherapy.
What were the results of the BRIGHT AML 1003 trial?
The BRIGHT AML 1003 trial showed that glasdegib in combination with low-dose cytarabine (LDAC) significantly improved overall survival and complete response rates compared to LDAC alone in newly diagnosed AML patients.
Did the BRIGHT AML 1019 trial meet its primary endpoint?
No, the BRIGHT AML 1019 trial did not meet its primary endpoint, as the addition of glasdegib to either intensive or non-intensive chemotherapy did not significantly improve overall survival.
What is the current market value of Hedgehog pathway inhibitors?
The Hedgehog pathway inhibitors market was valued at USD 1.32 billion in 2023 and is expected to grow to USD 3.89 billion by 2030.
What are the common adverse events associated with glasdegib?
Common adverse events associated with glasdegib include nausea, febrile neutropenia, anemia, and constipation, similar to those seen with chemotherapy alone.
Sources
- Sekeres MA, Montesinos P, Novak J, et al. Glasdegib plus intensive or non-intensive chemotherapy for untreated acute myeloid leukaemia: results from the randomized, phase 3 BRIGHT AML 1019 trial. Leukemia. 2023;37(10):2017-26.
- FDA Approval Summary: Glasdegib for Newly Diagnosed Acute Myeloid Leukemia. Clinical Cancer Research. 2018.
- Pharmacoeconomic Report for Glasdegib (DAURISMO). CADTH. 2020.
- Adding glasdegib to chemotherapy does not improve survival in patients with untreated AML. Belgian Journal of Hematology.
- Hedgehog Pathway Inhibitors Market by Generic Drug Name. 360iResearch. 2023.
Last updated: 2025-01-07
