FDA grants fast track status to investigational bepirovirsen for chronic hepatitis B
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The FDA has granted fast track designation to GSK’s bepirovirsen, a triple action investigational antisense oligonucleotide, for the treatment of chronic hepatitis B virus infection, according to a manufacturer release.
Developed jointly with Ionis Pharmaceuticals, bepirovirsen is intended to curb viral DNA replication, reduce the level of hepatitis B surface antigen and stimulate the immune system to boost the likelihood of a durable and sustained response.
The FDA based its decision on data from two phase 2b trials, B-Clear and B-Sure, which assessed the efficacy, safety and response durability of bepirovirsen in patients with chronic HBV.
The B-Clear trial included two patient cohorts consisting of those who received treatment with nucleoside/nucleotide analogues (NAs) and those who did not. Patients were randomly assigned to one of four treatment groups with bepirovirsen:
- Bepirovirsen 300 mg with loading doses (LD) for 24 weeks;
- Bepirovirsen 300 mg with LD for 12 weeks, then 150 mg for 12 weeks;
- Bepirovirsen 300 mg with LD for 12 weeks, then placebo for 12 weeks;
- Placebo with LD for 12 weeks, then bepirovirsen 300 mg without LD for 12 weeks.
According to the release, the B-Clear trial demonstrated that patients with low base hepatitis B surface antigen levels “were most likely to benefit from treatment with bepirovirsen.”
Compared with the NAs, bepirovirsen is “the only single agent in phase 3 development that has shown the potential to achieve clinically meaningful functional cure response when combined with oral nucleoside/nucleotide analogues,” the release noted. However, NAs can only hinder the virus itself, but do not lower hepatitis B surface antigen, which is critical for functional cure.
The B-Sure trial is currently investigating longer efficacy and response durability in bepirovirsen, following patients from the B-Clear trial who have stopped NA therapy for an additional 33 months. The B-Sure trial intends to assess “the potential for functional cure in patients who successfully stop all medication and continue to demonstrate no serologic evidence of hepatitis B surface antigen or HBV DNA,” the release stated.
Additionally, a confirmatory phase 3 trial, B-Well, is ongoing, the company noted.
FDA fast track designation is intended to expedite the development and review of drugs that fulfill an unmet need in serious diseases. Benefits of the designation include the potential for more frequent meetings with the FDA during clinical development, eligibility for accelerated approval or priority review, and the ability to submit sections of a biologics license application on a rolling basis.
Reference:
- Positive data for bepirovirsen from B-Clear phase IIb trial presented at American Association for the Study of Liver Diseases’ Meeting with simultaneous publication in the New England Journal of Medicine. https://www.gsk.com/en-gb/media/press-releases/positive-data-for-bepirovirsen-from-b-clear-phase-iib-trial/ Published Nov. 8, 2022. Accessed Feb. 13, 2024.
Perspective
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The news that the FDA has granted fast track designation for bepirovirsen is an exciting and historic update. It demonstrates that the FDA clearly recognizes that the lack of approved treatments that can achieve functional cure of chronic hepatitis B represents a critical unmet need.
Furthermore, it supports the encouraging data seen in the phase 2 B-Clear trial, which showed compelling evidence that functional cure can be achieved, particularly in individuals with lower HBsAg quantitative levels at baseline. No significant adverse events were noted, launching it as one of the promising new therapeutics on the horizon for HBV cure.
Hopefully, this will lead to support for its eventual approval with planned completion of the phase 3 B-Well program.
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