作者: Mayo, Marlyn J ; Yilmaz, Yusuf ; Crittenden, Daria B ; Jeong, Sook-Hyang ; Janczewska, Ewa ; Invernizzi, Pietro ; Vierling, John M ; Levy, Cynthia ; Kallis, Yiannis ; Buggisch, Peter ; Corpechot, Christophe ; Ladrón de Guevara Cetina, Alma L ; Hirschfield, Gideon M ; Choi, Yun-Jung ; Kremer, Andreas E ; Londoño Hurtado, Maria Carlota ; Zigmond, Ehud ; Yang, Ke ; McWherter, Charles A ; Bowlus, Christopher L ; Kowdley, Kris V ; Bergheanu, Sandrin ; Villamil, Alejandra

BACKGROUNDEffective treatments for patients with primary biliary cholangitis are limited. Seladelpar, a peroxisome proliferator-activated receptor delta agonist, has potential benefits.METHODSIn this phase 3, 12-month, double-blind, placebo-controlled trial, we randomly assigned (in a 2:1 ratio) patients who had had an inadequate response to or who had a history of unacceptable side effects with ursodeoxycholic acid to receive oral seladelpar at a dose of 10 mg daily or placebo. The primary end point was a biochemical response, which was defined as an alkaline phosphatase level less than 1.67 times the upper limit of the normal range, with a decrease of 15% or more from baseline, and a normal total bilirubin level at month 12. Key secondary end points were normalization of the alkaline phosphatase level at month 12 and a change in the score on the pruritus numerical rating scale (range, 0 [no itch] to 10 [worst itch imaginable]) from baseline to month 6 among patients with a baseline score of at least 4 (indicating moderate-to-severe pruritus).RESULTSOf the 193 patients who underwent randomization and treatment, 93.8% received ursodeoxycholic acid as standard-of-care background therapy. A greater percentage of the patients in the seladelpar group than in the placebo group had a biochemical response (61.7% vs. 20.0%; difference, 41.7 percentage points; 95% confidence interval [CI], 27.7 to 53.4, P<0.001). Normalization of the alkaline phosphatase level also occurred in a greater percentage of patients who received seladelpar than of those who received placebo (25.0% vs. 0%; difference, 25.0 percentage points; 95% CI, 18.3 to 33.2, P<0.001). Seladelpar resulted in a greater reduction in the score on the pruritus numerical rating scale than placebo (least-squares mean change from baseline, -3.2 vs. -1.7; least-squares mean difference, -1.5; 95% CI, -2.5 to -0.5, P = 0.005). Adverse events were reported in 86.7% of the patients in the seladelpar group and in 84.6% in the placebo group, and serious adverse events in 7.0% and 6.2%, respectively.CONCLUSIONSIn this trial involving patients with primary biliary cholangitis, the percentage of patients who had a biochemical response and alkaline phosphatase normalization was significantly greater with seladelpar than with placebo. Seladelpar also significantly reduced pruritus among patients who had moderate-to-severe pruritus at baseline. The incidence and severity of adverse events were similar in the two groups. (Funded by CymaBay Therapeutics; RESPONSE ClinicalTrials.gov number, NCT04620733; EudraCT number, 2020-004348-27.).

2022-10-01·Pathology3区 · 医学

Prevalence and clinical significance of portal inflammation, portal plasma cells, interface hepatitis and biliary injury in liver biopsies from patients with non-alcoholic steatohepatitis

3区 · 医学

Article

作者: Vierling, John M ; Dhingra, Sadhna ; Tarabishy, Yaman ; May, Sarah B ; Mahadik, Juhi D

The significance of portal tract histological changes in non-alcoholic fatty liver disease (NAFLD) remains unclear. In 2019, CymaBay Therapeutics halted clinical trials of seladelpar (a PPARδ agonist) because initial end-of-treatment liver biopsies of patients with non-alcoholic steatohepatitis (NASH) showed concerning features of portal inflammation with plasma cells, interface hepatitis and focal bile duct abnormalities. Adjudication concluded that these findings were present in the initial, as well as the subsequent biopsies. Thus, this study's aim was to determine the prevalence and clinical significance of portal inflammation, portal plasma cells, interface hepatitis and features of bile duct damage in liver biopsies of adult patients with NAFLD. The pathology database was searched for cases of NAFLD, including steatosis alone and NASH, from January 2016 to October 2020. Liver biopsies were selected from age and sex matched adult patients with diagnoses of steatosis alone (n=10), NASH fibrosis stage 1 (n=10), stage 2 (n=10), stage 3 (n=10), and stage 4 (n=10). There were 24 males and 26 females with a mean age of 48 years (range 20-79). Exclusion criteria included age <18 years, daily alcohol intake >14 drinks per week, elevation of alkaline phosphatase level, comorbid chronic liver disease, or liver biopsy performed as part of a clinical trial for NASH. Control liver biopsies were selected from age and sex matched persons without significant steatosis and normal liver biochemical tests (n=10). Histological parameters were evaluated in 10 portal tracts or 10 septal areas in each liver biopsy. Portal inflammation and interface hepatitis were graded on a scale of 0-4. Portal plasma cells and bile duct damage were scored from 0-3. Ductular proliferation was assessed by CK7 immunostain and graded from 0-4. NASH biopsies with advanced fibrosis (stage 3 and 4) showed portal inflammatory infiltrates (score 2-3) with readily identifiable plasma cells (score 2), and mild to moderate interface hepatitis (score 2-3). All cases and controls showed focal, mild cholangiocyte changes, characterised by cytoplasmic vacuolation, segmental loss of nuclei, nuclear disarray and apoptosis. NASH patients with advanced fibrosis had frequent and diffuse cholangiocyte changes, along with focal lymphocytic cholangitis and moderate to marked ductular reaction (score 3-4). Histopathological features of advanced NASH frequently include increased portal inflammation with plasma cells, interface hepatitis, cholangiocyte injury and prominent ductular reaction.

2017-01-01·Arthritis & Rheumatology1区 · 医学

Review: Gout: A Roadmap to Approaches for Improving Global Outcomes

1区 · 医学

Review

作者: Terkeltaub, Robert ; Dalbeth, Nicola ; Choi, Hyon K.

Gout: A roadmap to approaches for improving global outcomes Nicola Dalbeth 1 *, Hyon K. Choi 2 *, Robert Terkeltaub 3 *contributed equally to this manuscript Nicola Dalbeth MB ChB, MD, Bone & Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand. n.dalbeth@auckland.ac.nz Hyon K. Choi, MD, PhD, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA hchoi@mgh.harvard.edu Robert Terkeltaub, MD, VA San Diego Healthcare System, San Diego, CA, Dept. of Medicine, University of California San Diego, San Diego, CA rterkeltaub@ucsd.edu Supported by the Health Research Council of New Zealand (9101-3708025)(ND), NIH (R01AR065944)(HKC), and VA Research Service (RT). Dr. Dalbeth has received grant support from AstraZeneca and has participated on speaker bureaus for Menarini, ARDEA/Astra-Zeneca, Takeda, and as a consultant for Astra-Zeneca, Fonterra, Takeda, Pfizer, CymaBay, and Crealta. Dr. Choi has served as consultant for Takeda and ARDEA/Astra-Zeneca. Dr. Terkeltaub has served as a consultant for ARDEA/Astra-Zeneca, SOBI, Revive, Selecta, Aequus, ProteoThera, Horizon, Relburn, and CymaBay. Correspondence to: Robert Terkeltaub MD, VA San Diego Healthcare System, 111K, 3350 La Jolla Village Drive, San Diego, CA 92161. Telephone: 858 642 3519. Fax: 858 552 7425, email: rterkeltaub@ucsd.edu Running Head: Roadmap to improved gout outcomes Keywords: Hyperuricemia, ABCG2, URAT1, NLRP3 inflammasome, Precision Medicine

项与 CB 001 (CymaBay therapeutics) 相关的新闻（医药）

2023-11-07

·GlobeNewswire-Health Care

CymaBay Reports Third Quarter and Nine Months Ended September 30, 2023 Financial Results and Provides Corporate Update

Announced top-line results from RESPONSE Phase 3 study in PBC where seladelpar met the primary and two key secondary endpoints with high statistical significance. Seladelpar granted revised Breakthrough Therapy Designation for the treatment of PBC including pruritus in patients without cirrhosis or with compensated cirrhosis and are inadequate responders to or intolerant to UDCA. Announced oral late-breaking presentation of results from the RESPONSE global Phase 3 study evaluating seladelpar for Primary Biliary Cholangitis at The Liver Meeting® 2023. Completed a public offering of common stock and pre-funded warrants with net proceeds of $242.8 million. Initiated AFFIRM, a Phase 3b/4 study evaluating the effect of seladelpar on clinical outcomes in patients with cirrhosis due to PBC. Conference call and webcast today at 4:30 p.m. ET NEWARK, Calif., Nov. 07, 2023 (GLOBE NEWSWIRE) -- CymaBay Therapeutics, Inc. (NASDAQ: CBAY), a biopharmaceutical company focused on innovative therapies for patients with liver and other chronic diseases, today announced corporate updates and financial results for the third quarter ended September 30, 2023. Sujal Shah, President and CEO of CymaBay, stated, “This past quarter has been a momentous one for CymaBay where we achieved multiple significant milestones advancing us towards our goal of improving lives of people living with PBC. The consistency and depth of the clinical data set generated from Phase 2, ENHANCE and now RESPONSE demonstrates that seladelpar has the potential to be the first ever approved treatment for patients with PBC to significantly reduce both markers related to the risk of disease progression and symptoms. I am incredibly proud of the team here at CymaBay and commend them for the progress they helped achieve and equally grateful to patients and patient advocacy groups, their caregivers and our investigators for their partnership and support. We are eager to continue the positive momentum and are working diligently on our near-term milestones for seladelpar.” Corporate Updates: On September 7, 2023, we announced topline results from our seladelpar Phase 3 RESPONSE study. The study evaluated the safety and efficacy of seladelpar for the treatment of PBC. The trial achieved the primary and all key secondary endpoints. Primary composite endpoint at 12 months of serum alkaline phosphatase and bilirubin was met by 61.7% of patients treated with seladelpar 10 mg vs. 20.0% of placebo treated patients (p<0.0001)Normalization of alkaline phosphatase at 12 months was achieved by 25.0% of patients treated with seladelpar vs. 0% on placebo (p<0.0001)In patients having moderate-to-severe itch at baseline, the seladelpar treated group improved their pruritus at 6 months compared to those in the placebo group (p<0.005)Overall safety and tolerability were comparable between placebo and seladelpar groups and consistent with previous studiesTreatment-emergent adverse events, serious adverse events, and patient discontinuations were generally balanced across the treatment and placebo arms. There were no treatment-related serious adverse events in the study. On October 23, 2023, we announced that the U.S. Food and Drug Administration (FDA) has revised the originally granted Breakthrough Therapy Designation for seladelpar to now reflect treatment of primary biliary cholangitis (PBC) including pruritus in adults without cirrhosis or with compensated cirrhosis (Child Pugh A) and are inadequate responders to or intolerant to UDCA. Seladelpar is the only potent, selective, orally active PPARδ agonist, or delpar, with Phase 3 results demonstrating a statistically significant improvement in PBC-related cholestatic pruritus.A late-breaking presentation highlighting results from the RESPONSE Phase 3 study of seladelpar in patients with PBC will be presented at The Liver Meeting® of the American Association for the Study of Liver Diseases (AASLD), in Boston, MA (November 10th – 14th).Announced the initiation of AFFIRM, a randomized, placebo-controlled confirmatory study to evaluate the effect of seladelpar on clinical outcomes in patients with compensated cirrhosis due to PBC. The AFFIRM study is planned to enroll approximately 192 patients with PBC who have compensated cirrhosis (Child-Pugh A or Child-Pugh B) based on prespecified clinical criteria. Patients will be randomly assigned using a 2:1 ratio to oral, once daily seladelpar or placebo for a fixed duration of three years. The primary outcome measure is the time from start of treatment to the first occurrence of clinical events (all-cause death, liver transplant, hospitalization for other serious liver-related events, and progression to Child-Pugh C decompensated cirrhosis). Additional key outcomes include overall survival, liver transplant-free survival, and time to hospitalization for serious liver-related events.Continued enrollment in ASSURE, an open-label, long-term study of seladelpar in patients with PBC intended to collect additional long-term safety and efficacy data to support registration. There are now over 300 patients in this study taking seladelpar daily, including those from our prior studies of seladelpar and patients who have completed RESPONSE.Findings from post-hoc analysis of the Phase 3 ENHANCE study of seladelpar for the treatment of PBC, showing baseline intensity of patient-reported pruritus was associated with higher levels of serum IL-31 was presented at American College of Gastroenterology (ACG), by Professor Andreas E. Kremer, MD, Ph.D., MHBA, a leading authority in cholestatic pruritus from the University of Zurich. Featured results included novel aspects of the anti-pruritic and anti-cholestatic mechanisms of seladelpar, CymaBay’s first-in-class oral, selective PPARδ agonist, or "delpar," being investigated for the treatment of patients with PBC.Completed an upsized public equity offering in September 2023, in which we sold 14,521,307 shares of common stock at $17.13 per share and pre-funded warrants to purchase 583,771 shares of common stock at $17.1299 per underlying share. Net proceeds of the offering were $242.8 million, after deducting the underwriting discount and other offering expenses.The Phase 2a proof-of-pharmacology study to assess whether MBX-2982 can enhance glucagon secretion during insulin-induced hypoglycemia in subjects with type 1 diabetes (T1D) has been completed. The study found that there was no change in glucagon secretion during clamps in subjects with T1D dosed with MBX-2982 versus placebo. In contrast, healthy volunteers showed a glucose dependent increase in glucagon during hypoglycemia. Further, target engagement by MBX-2982 was demonstrated by increases in GLP-1 levels in subjects with T1D. While disappointing, the results demonstrate a well-designed and executed study that demonstrated pharmacodynamic action of MBX-2982 but without demonstrating the pharmacology needed to benefit the T1D population. The scientific questions were answered and CymaBay is not planning any further studies with MBX-2982. We would like to thank Dr. Richard Pratley and his team at the AdventHealth Research Institute in Orlando, Florida as well as ProSciento Inc., California for conducting a well-designed and executed study and The Leona M. and Harry B. Helmsley Charitable Trust for their support of the study through a grant to AdventHealth. We are also grateful to the patients with T1D and healthy volunteers for their participation in the study. Financial Updates: Held $438.8 million in cash, cash equivalents and investments as of September 30, 2023. We believe that cash and investments on hand are sufficient to fund CymaBay’s operating expenses into the first half of 2026. Third Quarter and Nine Months Ended September 30, 2023 Financial Results Collaboration revenue recognized for the nine months ended September 30, 2023 was $31.0 million and was associated with the collaboration and license agreement with Kaken Pharmaceutical Co., Ltd. (Kaken) entered into in January 2023, to develop and commercialize seladelpar in Japan. As reported earlier, this revenue was recognized upon completion of the initial technology transfer to Kaken in the second quarter of 2023. No incremental collaboration revenue was recognized for the three months ended September 30, 2023. Of the $34.2M upfront payment received from Kaken, $2.7 million remains deferred as of September 30, 2023 and will be recognized upon completion of the CymaBay’s ongoing clinical data delivery and CMC development performance obligations.Research and development expenses for the three months ended September 30, 2023, and 2022 were $20.0 million and $15.5 million, respectively. Research and development expenses for the nine months ended September 30, 2023 and 2022 were $58.1 million and $51.8 million, respectively. Research and development expenses for the three- and nine-month periods ended September 30, 2023 increased compared to the corresponding periods in 2022 driven by higher clinical activities supporting our clinical studies.General and administrative expenses for the three months ended September 30, 2023 and 2022 were $12.2 million and $5.9 million, respectively. General and administrative expenses for the nine months ended September 30, 2023 and 2022 were $32.1 million and $17.9 million, respectively. General and administrative expenses for the three and nine months ended September 30, 2023 were higher than the corresponding period in 2022 driven by investments to prepare for potential commercialization of seladelpar in PBC as well as an increase in other corporate expenses.Net loss for the three months ended September 30, 2023 and 2022 was $33.9 million and $24.5 million, or ($0.32) and ($0.28) per share, respectively. Net loss for the nine months ended September 30, 2023 and 2022 was $63.5 million and $79.4 million, or ($0.62) and ($0.90) per share, respectively. Net loss for the three months ended September 30, 2023 was higher than the three months ended September 30, 2022 primarily due to higher operating expenses. Net loss for the nine months ended September 30, 2023 was lower than the corresponding periods in 2022 due primarily to the recognition of $31.0 million of collaboration revenue related to the Kaken upfront payment during the second quarter of 2023 and higher interest income earned on our investments and other income due to refundable tax credits, offset in part by an increase in operating expenses. Overall, we expect operating expenses to increase in the future as we continue to support our ongoing drug development activities and expand on initiatives to prepare for potential commercialization of seladelpar in PBC. Conference Call Details CymaBay will host a conference call today at 4:30 p.m. ET to discuss third quarter financial results and provide a business update. To access the live conference call, please dial 1-877-407-0784 from the U.S. and Canada, or 1-201-689-8560 internationally, Conference ID #13740701. To access the live and subsequently archived webcast of the conference call, go to the Investors section of the company's website at http://ir.cymabay.com/events. 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 through a pipeline of innovative therapies. 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 (U.S. Food and Drug Administration), Priority Medicines status (European Medicines Agency) and orphan drug status (U.S. and Europe) for seladelpar, a first-in-class investigational treatment for people with PBC. Our evidence-based decision-making and commitment to the highest quality standards reflect our relentless dedication to the people, families and communities we serve. To learn more, visit www.cymabay.com and follow us on X (formerly Twitter) and LinkedIn. Cautionary Statements Any statements made in this press release regarding the potential approval, launch and commercialization of seladelpar or timing or plans in regard thereto, as well as statements regarding the Company’s expected cash runway, potential benefits of seladelpar, the ability to enroll and/or complete the AFFIRM study, completion of ongoing clinical trials and subsequent regulatory submissions 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; effects observed in trials to date that may not be repeated in the future; any delays or inability to obtain or maintain regulatory approval of CymaBay's product candidates in the United States or worldwide; and the ability of CymaBay to obtain sufficient financing to complete development, regulatory approval and commercialization of its product candidates in the United States and worldwide. 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 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 Contact: Theresa DolgeEvoke Kyne(609) 915-2156Theresa.Dolge@evokegroup.com Investor Relations Contact: Hans VitzthumLifeSci Advisors, LLC(617) 430-7578Hans@LifeSciAdvisors.com CymaBay Therapeutics, Inc. Financial Results (In thousands, except share and per share information) Quarter Ended Nine Months Ended September 30, September 30, 2023 2022 2023 2022 (unaudited) (unaudited) (unaudited) (unaudited) Collaboration revenue - - 31,016 $- Operating expenses: Research and development 19,962 15,459 58,050 51,765 General and administrative 12,245 5,904 32,147 17,869 Total operating expenses 32,207 21,363 90,197 69,634 Loss from operations (32,207) (21,363) (59,181) (69,634) Other income (expense), net: Interest income 3,170 677 7,810 1,096 Interest expense (4,843) (3,819) (13,864) (10,832) Other income (2) - 1,767 2 Total other income (expense), net (1,675) (3,142) (4,287) (9,734) Net loss $(33,882) $(24,505) $(63,468) $(79,368) Basic and diluted net loss per common share $(0.32) $(0.28) $(0.62) $(0.90) Weighted average common shares outstanding used to calculate basic and diluted net loss per common share 105,717,996 87,804,272 101,974,866 87,803,388 CymaBay Therapeutics, Inc. Balance Sheet Data (in thousands) September 30, December 31, 2023 2022 (unaudited) Cash, cash equivalents and marketable securities $438,778 $135,485 Working capital 427,993 122,632 Total assets 451,048 141,852 Total liabilities 124,857 105,698 Common stock and additional paid-in capital 1,262,578 909,337 Total stockholders’ equity 326,191 36,154

临床结果突破性疗法临床2期临床3期孤儿药

2023-10-23

·BioSpace

CymaBay Presents Results on the Potential of Seladelpar in Treatment of Patients with Primary Biliary Cholangitis at ACG 2023

Cholestatic pruritus expert leads plenary discussion of correlated decreases in serum IL-31 levels and pruritus among patients with PBC treated with seladelpar A second presentation of baseline trial data suggests that any elevation in key liver biomarkers may put PBC patients at risk for disease progression and poor outcomes VANCOUVER, British Columbia, Oct. 23, 2023 (GLOBE NEWSWIRE) -- CymaBay Therapeutics, Inc. (NASDAQ: CBAY), a biopharmaceutical company focused on innovative therapies for patients with liver and other chronic diseases, announced today the presentation of findings from its post-hoc analysis of the Phase 3 ENHANCE study of seladelpar for the treatment of primary biliary cholangitis (PBC), showing baseline intensity of patient-reported pruritus was associated with higher levels of serum IL-31. The presentation, named the recipient of this year’s International Award by the American College of Gastroenterology, will be presented by Professor Andreas E. Kremer, MD, Ph.D., MHBA, a leading authority in cholestatic pruritus from the University of Zurich. Featured results included novel aspects of the anti-pruritic and anti-cholestatic mechanisms of seladelpar, CymaBay’s first-in-class oral, selective PPARδ agonist, or "delpar," being investigated for the treatment of patients with PBC. The data were previously presented at the European Association for the Study of the Liver (EASL)’s The International Liver Congress™ 2023 in Vienna, Austria. “Despite pruritus being an excruciating symptom experienced by many patients with PBC, to date, there has been limited understanding of the underlying pathology of itch and how to effectively treat this issue,” said Dr. Kremer. “These results offer a glimmer of hope in that they link IL-31 levels in patients with PBC to itch. What we are seeing in our research is that treatment with seladelpar is correlated with a significant decrease in both IL-31 levels and levels of patient-reported itch. This is a unique opportunity for researchers to further explore the relationship between the IL-31 pathway and itch, which may help us improve how we address an important, and often distressing, unmet need for patients.” The company also presented a post-hoc analysis of four seladelpar clinical trials from 2015 to 2022, which found that PBC patients previously treated with ursodeoxycholic acid (UDCA, the first-line therapy for PBC) with elevated alkaline phosphatase (ALP) who did not meet current clinical guidelines for second-line treatment, nevertheless had a significant risk of disease progression. “Across our clinical trials, we see that patients with any level of ALP elevation have multiple factors that pose a risk for disease progression, even though many of them do not meet the current requirements for second-line treatment under current treatment guidelines,” said Charles McWherter, Ph.D., Chief Scientific Officer and President of Research and Development at CymaBay. “We already know there is an unmet need for treatment options for patients with this rare, devastating liver disease. These data suggest there may be an even greater number of patients who could benefit from earlier treatment to slow disease progression than are currently accounted for in medical practice.” Presentation Details: Seladelpar treatment resulted in correlated decreases in serum IL-31 and pruritus in patients with PBC: post-hoc results from the Phase 3 randomized, placebo-controlled ENHANCE study October 23rd 2:35pm – 2:45pm PT Presentation 17, Plenary Session 1B - Liver Presenter: Andreas Kremer A post-hoc analysis of the Phase 3 ENHANCE trial showed a correlation between serum IL-31 levels and self-reported pruritus improvements in patients with PBC after three months of treatment with seladelpar. This included seladelpar 5 mg (3.8 to 1.7 pg/mL, p < 0.001), 10 mg (4.2 to 1.7 pg/mL, p < 0.001) compared to placebo (4.3 to 3.9 pg/mL, not significant). The IL-31 pathway is a validated therapeutic target for pruritus in other diseases, such as atopic dermatitis. Patients with clinically meaningful improvement in pruritus (≥ 2 decreases in numerical rating scale, or NRS, score) showed greater dose-dependent reductions in IL-31 from baseline than those without pruritus improvement. Significant correlations were also observed between changes in IL-31 versus reported pruritus NRS scores (r = 0.54, p < 0.0001), alkaline phosphatase (ALP) levels (r = 0.40, p <0.01), and total bile acids (r = 0.63, p < 0.0001) in the seladelpar 10mg group. These results suggest a relationship between IL-31 levels and severity of itch, a symptom associated with PBC that remains an outstanding unmet need for patients. The ACG International Award for this abstract will be presented to Dr. Kremer during the ACG Awards Reception, taking place from 6:30 to 7:30 p.m. on Monday, October 23, 2023 in Room 302 at the Vancouver Convention Center. Baseline characteristics and risk profiles of 1111 patients with PBC in need of second-line therapy October 24th 10:30am – 4:00pm PT Poster #P3788 Presenter: Gideon Hirschfield A post-hoc analysis of four seladelpar clinical trials from 2015 to 2022 looked at 1111 patients in 27 countries with PBC after treatment with UDCA for greater than or equal to 12 months, or who had intolerance to UDCA. The analysis compared the baseline characteristics and risk profiles of PBC patients with elevated ALP levels (greater than or equal to 1.67x upper limit of normal, or ULN) to patients who did not meet this standard ALP threshold for inclusion yet still had a slightly elevated ALP level (above ULN, but below 1.67x ULN). Additional elevated risk was identified based on Enhanced Liver Fibrosis (ELF) scores and liver stiffness using Fibroscan®. Elevated risk due to ELF was identified in 43.2% of patients who currently meet guidelines for second-line treatment vs. 27.2% within patient groups not recommended for second-line treatment. The data showed that patients previously treated with UDCA with persistent elevation of ALP, but who were not currently recommended by guidelines for second-line treatment, had a significant risk for disease progression, highlighting the need for second-line therapy for a broader patient group. 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 US). PBC is characterized by impaired bile flow (known as cholestasis) and the accumulation of toxic bile acids in the liver, leading to inflammation and destruction of the bile ducts within the liver and causing increased levels of ALP and total bilirubin. The most common early symptoms of PBC are pruritus (itching) and fatigue, which can be debilitating for some patients. Progression of PBC is associated with an increased risk of liver-related mortality. About Seladelpar Seladelpar, an investigational treatment for people with PBC, is a first-in-class oral, selective peroxisome proliferator-activated receptor (PPAR) delta 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 through a pipeline of innovative therapies. 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 (U.S. Food and Drug Administration), Priority Medicines status (European Medicines Agency) and orphan drug status (U.S. and Europe) for seladelpar, a first-in-class investigational treatment for people with PBC. Our evidence-based decision-making and commitment to the highest quality standards reflect our relentless dedication to the people, families, and communities we serve. To learn more, visit and follow us on X (formerly Twitter) and LinkedIn. Cautionary Statements Any statements made in this press release regarding the potential for seladelpar to treat PBC and potentially improve clinical symptoms of the disease, the potential benefits to patients and the future filing plans of CymaBay 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 . Public Relations Contact: Theresa Dolge Evoke Kyne (609) 915-2156 Theresa.Dolge@evokegroup.com Investor Relations Contact: Hans Vitzthum LifeSci Advisors, LLC (617) 430-7578 Hans@LifeSciAdvisors.com

临床结果临床3期突破性疗法孤儿药

2023-09-07

·Firstwordpharma

CymaBay jumps on data for primary biliary cholangitis therapy seladelpar

Shares of CymaBay Therapeutics gained as much as 23% on Thursday after the company reported that its investigational drug seladelpar achieved the main objectives in a Phase III study of patients with primary biliary cholangitis (PBC). The RESPONSE trial data support filing for approval of the treatment with US and European regulators, the company said.The RESPONSE study randomised 193 PBC patients to receive once-daily seladelpar or placebo. Eligible participants had an inadequate response or intolerance to ursodeoxycholic acid with serum alkaline phosphatase (ALP) ≥1.67 times the upper limit of normal (ULN) after at least 12 months of treatment.The primary outcome measure was responder rate, defined as achieving an ALP level <1.67 times ULN with ≥15% decrease in ALP, and total bilirubin ≤1.0 times ULN, after one year. According to CymaBay, top-line results showed that 61.7% of patients treated with seladelpar met this endpoint, compared with 20% for placebo.It said the drug's anti-cholestatic effect was supported by the fact that 25% of patients achieved normalisation of ALP at 12 months, a key secondary endpoint of the study, compared to none in the placebo group. There was a substantial 42.4% reduction in the least-squares mean percent of ALP in the seladelpar group over that time, versus a 4.3% reduction among placebo recipients.Relief from incessant itchingThe study also succeeded on the key secondary goal of reduction in pruritis after six months of treatment. Seladelpar-treated patients with a baseline Numerical Rating Scale (NRS) ≥4, indicating moderate-to-severe itch, had a least-square mean reduction of 3.2 points in pruritus NRS, compared to 1.7 points for patients in the placebo group.CymaBay noted that treatment-emergent adverse events, serious side effects and patient discontinuations were "generally balanced" across the two arms. There were also no treatment-related serious adverse events in the study. Researchers are conducting more analyses, and the company says it plans to share additional data at an upcoming medical meeting."We believe that the delpar mechanism is unique with its ability to normalise markers of cholestasis coupled with reductions in pruritus," remarked CEO Sujal Shah, adding "these results represent an important step toward potentially changing the treatment paradigm for patients living with PBC."

临床结果临床3期

100 项与 CB 001 (CymaBay therapeutics) 相关的药物交易

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