CM-101 is an investigational, first-in-class, monoclonal antibody designed to neutralize CCL24, a soluble protein that regulates biliary inflammation and fibrosis in patients with fibroinflammatory diseases such as PSC.

The designation is supported by data from a phase 2a trial (ClinicalTrials.gov Identifier: NCT05824156), which evaluated the safety and tolerability of CM-101 in adults with noncirrhotic nonalcoholic steatohepatitis (NASH) with stage 1c, 2, or 3 fibrosis. Results showed that treatment with CM-101 achieved consistent, positive improvements in key inflammatory and fibrogenesis-related biomarkers.

The Company is investigating CM-101 in adults with PSC in the ongoing double-blind, placebo-controlled, phase 2 SPRING trial (ClinicalTrials.gov Identifier: NCT04595825). Topline data from the SPRING study is expected to be available in the second half of 2024.

“This FDA Fast Track designation is an important validation of CM-101’s potential to have a major impact on this devastating disease that attacks people in their prime years and lacks any approved treatments,” said Adi Mor, PhD, co-founder, CEO and Chief Scientific Officer of Chemomab. “We designed the CM-101 phase 2 SPRING trial to be supportive of a registrational trial in patients with PSC, and we welcome the enhanced opportunities for working closely with the FDA and for acceleration of the development and review process provided by Fast Track status.”

HealthDay News — Curcumin and omeprazole have similar efficacy for functional dyspepsia, according to a study published online September 11 in BMJ Evidence-Based Medicine.

Pradermchai Kongkam, MD, from the Chulalongkorn University Faculty of Medicine in Bangkok, and colleagues conducted a randomized trial to compare the efficacy of curcumin versus omeprazole for patient-reported outcomes among participants with a diagnosis of functional dyspepsia. Two hundred six patients were randomly assigned to one of three groups: curcumin alone (C), omeprazole alone (O), and curcumin plus omeprazole (C+O). The Severity of Dyspepsia Assessment (SODA) score was used to assess symptoms of functional dyspepsia on days 28 and 56.

The researchers found that on day 28, there were significant improvements in SODA scores in the pain, nonpain, and satisfaction categories for the C+O, C, and O groups. On day 56, these improvements were enhanced in the pain, nonpain, and satisfaction categories in all groups. There were no significant differences seen among the groups and no reports of serious adverse events.

“To the best of our knowledge, this study represents the first head-to-head comparison demonstrating the efficacy of curcumin in treating functional dyspepsia compared with omeprazole,” the authors write. “Curcumin and omeprazole were both effective for functional dyspepsia and did not appear to have a synergistic effect.”

Abstract/Full Text

Elafibranor is an oral, dual peroxisome activated receptor alpha and delta (PPAR alpha/delta) agonist. The application is supported by data from the phase 3 ELATIVE trial (ClinicalTrials.gov Identifier: NCT04526665), which included 161 patients with PBC who had an inadequate response or intolerance to UCDA. 

Study participants were randomly assigned 2:1 to receive elafibranor 80mg once daily or placebo. The primary endpoint was biochemical response, defined as alkaline phosphatase (ALP) of less than 1.67 x upper limit of normal (ULN), an ALP decrease of 15% or greater and total bilirubin of ULN or less, at 52 weeks.

Findings showed 51% of patients treated with elafibranor achieved a biochemical response compared with 4% of those who received placebo (placebo-adjusted difference, 47%; P <.001). Normalization of ALP (key secondary endpoint) was achieved by 15% of patients in the elafibranor arm and none of the patients in the placebo arm (P =.002). Among elafibranor-treated patients, reductions in ALP were seen as early as week 4 and sustained through week 52 (decrease in ALP of 41% on elafibranor vs placebo). 

Though a reduction in pruritus was observed with elafibranor (based on PBC Worst Itch Numeric Rating Scale score), this endpoint was not considered statistically significant. The most common adverse reactions reported with elafibranor were abdominal pain, diarrhea, nausea, and vomiting.

“[PBC] is a condition where many patients are living with worsening disease and debilitating symptoms despite being on treatment,” said Christelle Huguet, EVP and Head of Research & Development, Ipsen. “Elafibranor, if approved, has the potential to change the management of this challenging condition for people living with PBC, offering a new second line treatment choice, where the number of effective options are currently limited.”

A regulatory decision is expected on June 10, 2024.

The table below is a review of notable updates that occurred in June 2023 for investigational products in development (not an inclusive list). Click on the status to view our full coverage.

The Food and Drug Administration (FDA) has accepted for Priority Review the supplemental New Drug Application (sNDA) for odevixibat, an ileal bile acid transporter inhibitor, for the treatment of Alagille syndrome.

The sNDA is supported by data from the randomized, double-blind, placebo-controlled phase 3 ASSERT study (ClinicalTrials.gov Identifier: NCT04674761), which included 63 patients less than 17 years of age with a genetically confirmed diagnosis of Alagille syndrome. Patients were randomly assigned to receive either odevixibat or placebo orally once daily for 24 weeks. 

Results showed that treatment with odevixibat met the primary endpoint demonstrating a statistically significant reduction in pruritus at month 6, as measured by the PRUCISION Observer-Reported Outcome scratching score, compared with placebo (P =.002). Additionally, a statistically significant reduction in serum bile acid concentration (secondary endpoint) from baseline to the average of weeks 20 and 24 was observed with odevixibat vs placebo (P =.001).

Odevixibat was well tolerated in the study; the incidence of overall adverse events was similar to placebo. Drug-related diarrhea was reported in 11.4% of odevixibat-treated patients and 5.9% of placebo-treated patients.

Odevixibat is currently marketed under the brand name Bylvay^® for the treatment of progressive familial intrahepatic cholestasis. The application for the Alagille syndrome indication has been assigned a Prescription Drug User Fee Act target date of June 15, 2023.

References

1. FDA grants June 15, 2023 PDUFA date to Albireo for Bylvay^® in Alagille syndrome. News release. Albireo Pharma, Inc. Accessed February 14, 2023. https://www.globenewswire.com/news-release/2023/02/14/2607628/0/en/FDA-Grants-June-15-2023-PDUFA-Date-to-Albireo-for-Bylvay-in-Alagille-Syndrome.html.
2. Bylvay^® (odevixibat) data presented at AASLD The Liver Meeting^® 2022, demonstrating native liver survival in children across PFIC types. News release. Albireo Pharma, Inc. November 7, 2022. Accessed February 14, 2023. https://ir.albireopharma.com/news-releases/news-release-details/bylvayr-odevixibat-data-presented-aasld-liver-meetingr-2022.

The Food and Drug Administration (FDA) has cleared RELiZORB (immobilized lipase) cartridge for use in pediatric patients aged 2 to less than 5 years old experiencing fat malabsorption.

RELiZORB is a digestive enzyme cartridge designed to hydrolyze fats contained in enteral formulas, mimicking the function of lipase. This allows for the delivery of absorbable fatty acids and monoglycerides to patients. The treatment was initially approved in 2015 for adults and subsequently gained approval for pediatric patients 5 years of age and older in 2017.

The expanded approval for younger patients was based on a retrospective evaluation of real-world data. According to Alcresta Therapeutics, no additional safety concerns were identified in patients 2 to less than 5 years old who received enteral formula administered through RELiZORB as part of an enteral feeding regimen.

RELiZORB is supplied as single-use cartridges and connects in-line to enteral feeding systems. As the enteral formula passes through the cartridge, the fat is hydrolyzed as it comes in contact with iLipase^®, the Company’s proprietary technology that consists of lipase bound to small polymeric bead carriers.

“This additional RELiZORB clearance represents access for approximately 25% of the cystic fibrosis enterally fed market and for enterally fed pediatric patients ages 2 to less than 5 years suffering from conditions that contribute to fat malabsorption,” said Dan Orlando, CEO at Alcresta Therapeutics.

Seladelpar is an investigational, first-in-class oral, selective peroxisome proliferator-activated receptor delta agonist (or delpar). The application is supported by data from multiple trials including the phase 3 RESPONSE (ClinicalTrials.gov Identifier: NCT04620733) and ENHANCE (ClinicalTrials.gov Identifier: NCT03602560) studies. The trials enrolled patients with PBC who had an inadequate response or intolerance to ursodeoxycholic acid. 

The primary endpoint of both studies was a composite of serum alkaline phosphatase and total bilirubin. Findings showed treatment with seladelpar led to a statistically significant improvement in biochemical markers of disease progression compared with placebo. Additionally, a statistically significant reduction in pruritus was observed with seladelpar vs placebo.

“We are encouraged by the agency’s decision to grant Priority Review for seladelpar, and its recognition of the significant need for new treatment options for people living with PBC,” said Klara Dickinson, Chief Regulatory and Compliance Officer, CymaBay Therapeutics. “If approved, we believe seladelpar has the potential to raise the bar in second-line treatment of PBC by reducing markers of disease progression and improving pruritus, so we look forward to continued discussion with the agency throughout its review.”

A Prescription Drug User Fee Act target date of August 14, 2024 has been set for the application.