The New England Journal of Medicine Publishes Positive Phase 3 RESPONSE Data of CymaBay's Seladelpar in Primary Biliary Cholangitis
- Seladelpar demonstrated rapid and sustained improvements in reducing cholestasis and liver injury.
- Significant reductions in pruritus were observed across various scales in patients with PBC.
- The primary endpoint of ALP and total bilirubin normalization at Month 12 was achieved in 61.7% of patients treated with seladelpar.
- Key secondary endpoints like ALP normalization, reduction in ALT, and GGT levels were also significantly better in seladelpar-treated patients.
- Improvements in pruritus were seen as early as Week 4 and sustained through Month 12.
- The safety profile of seladelpar was favorable with no significant differences in adverse events compared to placebo.
- A New Drug Application (NDA) for seladelpar has been accepted for priority review by the FDA for the treatment of PBC.
- None.
Insights
The clinical trial results for seladelpar indicate a significant advancement in the treatment of primary biliary cholangitis (PBC), particularly in addressing pruritus, which is a common and distressing symptom for patients. The RESPONSE Phase 3 trial data, showing a high percentage of patients achieving the primary endpoint of ALP and total bilirubin normalization, suggest that seladelpar could become a leading therapy in the PBC market, especially for patients who have an inadequate response to the current first-line treatment, ursodeoxycholic acid (UDCA).
Furthermore, the safety profile of seladelpar appears comparable to placebo, with no serious adverse events linked to the treatment. This is crucial for patient compliance and long-term management of the disease. The New Drug Application (NDA) acceptance by the FDA for priority review and the breakthrough designation previously granted could expedite the availability of seladelpar to patients, potentially altering the current treatment paradigm for PBC.
The acceptance of seladelpar's NDA for priority review by the FDA, coupled with the breakthrough designation and PRIME status by the EMA, underscores the unmet medical need in the PBC treatment landscape. If approved, seladelpar could command a significant market share, given the drug's potential to offer better efficacy and safety than existing treatments. This could lead to increased healthcare spending in the short term due to the introduction of a novel therapy, but potentially reduce long-term costs associated with the management of PBC complications. Insurers and healthcare providers will need to assess the cost-effectiveness of seladelpar in comparison to existing therapies.
The publication of the Phase 3 trial results in a prestigious journal like The New England Journal of Medicine provides validation for CymaBay Therapeutics' research and development efforts. The market's reaction to such a publication is typically positive, as it not only raises awareness among healthcare professionals but also among investors. The detailed data suggest that seladelpar has a strong efficacy profile, which could lead to a competitive advantage in the market. The potential approval and subsequent market entry of seladelpar could significantly impact CymaBay's financial performance and stock valuation, as the company could capture a new segment of the PBC market, particularly among patients who are intolerant or non-responsive to UDCA.
- Seladelpar demonstrated normalization of liver biomarkers and significant reductions across three measures of patient-reported itch vs. placebo -
RESPONSE was a double-blind, placebo-controlled, global study of one-year duration that randomized 193 people with PBC in a 2:1 ratio to receive seladelpar 10 mg or placebo, once daily. Eligible participants had an inadequate response or intolerance to ursodeoxycholic acid (UDCA) with alkaline phosphatase, or ALP ≥ 1.67× the upper limit of normal (ULN) after at least 12 months of treatment. The primary endpoint was a composite of ALP and total bilirubin at Month 12, which supported authorization for current second line treatment in PBC by the
"Many people living with PBC do not experience a normalization of ALP or meaningful symptom relief with currently available treatments. Pruritus or severe itch significantly impairs the quality of life of our patients, and current second-line treatment frequently worsens itch. New options, that are potent, effective, and safe, are needed for people living with this chronic debilitating autoimmune condition," said Gideon Hirschfield, M.D., Lily and Terry Horner Chair in Autoimmune Liver Disease Research, Toronto Centre for Liver Disease. "The RESPONSE data are genuinely exciting. The data, together with the existing substantial experience gained from prior studies, robustly support the potential for seladelpar to raise the bar in PBC treatment. In this rigorous international trial, people living with PBC saw substantial rates of normalization of serum liver tests, and clear statistically significant improvement in itch. Benefits were also noted in those people living with compensated cirrhosis."
The key secondary endpoint of ALP normalization was reached in
The study also measured change in patient-reported pruritus as a key secondary endpoint using the daily numerical rating scale (NRS; 0-10). Approximately
Safety as reflected in adverse events (AEs) was similar in the seladelpar-treated and placebo-treated groups. The most common adverse events (AEs) in the study overall (≥
"The publication of the pivotal Phase 3 data for seladelpar in The New England Journal of Medicine recognizes the importance of these findings, the potential of this investigational agent to help people living with PBC, and the significant need for innovation in this area," said Charles McWherter, Ph.D., Chief Scientific Officer and President of Research and Development at CymaBay. "We are thrilled that these results are now available to benefit researchers, patients, and the broader medical community in our collective pursuit of PBC treatment transformation."
A New Drug Application (NDA) for seladelpar for the treatment of primary biliary cholangitis, including pruritus in adults without cirrhosis or with compensated cirrhosis (Child Pugh A) who are inadequate responders or intolerant to UDCA, was accepted for priority review by the FDA in February 2024. This application reflects the updated breakthrough designation that was granted by the agency in October 2023. The company also plans to file marketing authorization applications in the first half of 2024 with the EMA where seladelpar has received Priority Medicines (PRIME) status and plans to file with the
About PBC
PBC is a rare, chronic inflammatory liver disease primarily affecting women (1 in 1,000 women over the age of 40 or about 130,000 total people in the
About Seladelpar
Seladelpar, an investigational treatment for people with PBC, is a first-in-class oral, selective PPARδ agonist, or delpar, shown to regulate critical metabolic and liver disease pathways in indications with high unmet medical need. Preclinical and clinical data support its ability to regulate genes involved in bile acid synthesis, inflammation, fibrosis and lipid metabolism, storage, and transport.
About CymaBay
CymaBay Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on improving the lives of people with liver and other chronic diseases that have high unmet medical need. Our deep understanding of the underlying mechanisms of liver inflammation and fibrosis, and the unique targets that play a role in their progression, have helped us receive breakthrough therapy designation (FDA), PRIME status (EMA), and orphan drug status (
Cautionary Statements
Any statements made in this press release regarding potential FDA acceptance of the seladelpar NDA, the potential for seladelpar to treat PBC and potentially improve ALP levels, clinical symptoms or outcomes of the disease, the future EMA and MHRA filing plans of CymaBay and the timing thereof are forward-looking statements that are subject to risks and uncertainties. Actual results and the timing of events regarding the further development of seladelpar could differ materially from those anticipated in such forward-looking statements as a result of risks and uncertainties, which include, without limitation, risks related to: the success, cost and timing of any of CymaBay's product development activities, including clinical trials; and effects observed in trials to date that may not be repeated in the future. Additional risks relating to CymaBay are contained in CymaBay's filings with the Securities and Exchange Commission, including without limitation its most recent Annual Report on Form 10-K, its Quarterly Reports on Form 10-Q and other documents subsequently filed with or furnished to the Securities and Exchange Commission. CymaBay disclaims any obligation to update these forward-looking statements except as required by law.
For additional information about CymaBay visit www.cymabay.com.
Public Relations Contacts:
Theresa Dolge
Inizio Evoke
(609) 915-2156
theresa.dolge@inizioevoke.com
Arran Attridge
CymaBay Therapeutics
aattridge@cymabay.com
Investor Relations Contact:
PJ Kelleher
LifeSci Advisors, LLC
(617) 430-7579
pkelleher@LifeSciAdvisors.com
View original content to download multimedia:https://www.prnewswire.com/news-releases/the-new-england-journal-of-medicine-publishes-positive-phase-3-response-data-of-cymabays-seladelpar-in-primary-biliary-cholangitis-302068089.html
SOURCE CymaBay Therapeutics
FAQ
What are the key findings of the RESPONSE Phase 3 trial for seladelpar in treating primary biliary cholangitis (PBC)?
What was the primary endpoint achievement in patients treated with seladelpar?
What were the key secondary endpoints reached by patients treated with seladelpar?
What improvements were observed in pruritus in patients with PBC?
What is the safety profile of seladelpar compared to placebo?