89Bio Takes Major Step Forward in NASH Race With Mid-Stage Win

On Wednesday, 89bio announced that the data from the Phase IIb ENLIVEN trial revealed that their pegozafermin had achieved its primary histology endpoint and reduced fibrosis in a quarter of patients suffering from the serious liver condition, nonalcoholic steatohepatitis (NASH). This is an exciting breakthrough for NASH patients, offering the potential for an effective treatment.

An astounding 27% of patients taking a 44-mg dose of pegozafermin every two weeks saw a one-stage improvement in fibrosis without any worsening of other NASH symptoms – a far better result than the placebo group of 7%, and only marginally less than the 26% of patients taking a weekly 30-mg dose.

Pegozafermin proved to be an effective treatment for NASH resolution, with 26% of patients in the 44-mg dose group and 23% of patients in the 30-mg dose group achieving the desired result, compared to a mere 2% in the placebo group. Not only did these impressive results demonstrate the efficacy of Pegozafermin, but also the fact that it did not cause any worsening of fibrosis.

Shares of the company skyrocketed by an incredible 47% in response to the newly released data, sending shockwaves through the market.

Hank Mansbach, chief medical officer at 89bio, announced Wednesday morning that the clinical trial results for their NASH drug, pegozafermin, compare very favorably to those of other medications in development. On a placebo-adjusted basis, the drug was found to be highly effective.

89bio’s pegozafermin proved to be 3.5 times more effective than placebo, while Madrigal’s resmetirom scored 1.7 to 1.9 times better than the placebo. Novo Nordisk’s semaglutide achieved a placebo-adjusted drug-response estimate of 1.3, and Intercept’s ocaliva followed close behind with a result of 2.3. These results demonstrate the impressive efficacy of these treatments in clinical trials.

By comparing the drug response to the placebo response within a trial, meaningful insights can be gained despite the differences in trial designs and biopsy reading methodologies.

Despite the differences in protocols, it is not yet possible to make a definitive comparison between the various trials. Unfortunately, no direct comparison trials have been conducted to date. This is a shame, as it would provide invaluable information on the most effective treatments.

Pegozafermin is a unique engineered glycoPEGylated form of the hormone fibroblast growth factor 21, offering a range of benefits such as lipid metabolism, glycemic control, triglyceride reduction, and fibrosis. This revolutionary molecule has the potential to revolutionize the way we approach health and wellness, helping us to stay healthy and fit.

The ENLIVEN study showed positive results for pegozafermin treatment in terms of improved fibrosis and NASH disease activity, as well as decreased liver fat and other indicators of liver inflammation. Furthermore, HbA1c levels and lipid markers were also improved.

During the call, Mansbach reported that pegozafermin had a favorable adverse event profile, and was generally well-tolerated with only mild gastrointestinal side effects reported. The most commonly experienced symptoms were diarrhea, nausea, injection site erythema, injection site rashes, and increased appetite, all of which were grade 1 or 2. Safety-wise, pegozafermin was in line with what had been observed in prior studies.

The ENLIVEN study revealed a consistent safety profile, with only one patient experiencing a drug-related serious adverse event of uncomplicated pancreatitis and five out of 192 dropping out of the study due to side effects. This result is in line with the safety profiles of other NASH studies.

A Race to the Finish

In December 2022, Madrigal’s MAESTRO-NASH study Phase III data showed that its resmetirom had promising results in treating NASH. The study’s low treatment discontinuation rates ranged from 2.8% to 7.7%, with gastrointestinal events as the most common side-effect. The results of Madrigal’s candidate were comparable to those of pegozafermin, indicating potential for further development.

In January 2023, ChemomAb’s CM-101 achieved remarkable success in its Phase IIa study, proving to be both safe and highly effective. Patients reported minimal injection site reactions and anti-drug antibodies were absent. The majority of side effects were mild, with only one serious adverse event reported, unrelated to the drug. CM-101’s success is a promising sign for the future of healthcare.

Two new players are entering the NASH race – Akero Therapeutics and Hepion. Akero is gearing up for a Phase III study of its drug efruxifermin later this year, while Hepion is leveraging the power of Artificial Intelligence to accelerate its drug development efforts. Both companies are working to make an impact in the NASH space.

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