FDA puts pevifoscorvir sodium for hepatitis B on fast track
Experimental oral therapy has so far been well tolerated in ongoing clinical trial
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The U.S. Food and Drug Administration (FDA) has granted fast-track designation to pevifoscorvir sodium, Aligos Therapeutics‘ oral therapy candidate for chronic hepatitis B, which is now being tested in patients in a global clinical trial.
Fast-track status is intended to expedite the clinical development and regulatory review of treatments with the potential to address an unmet medical need for serious conditions. It allows more frequent communication with the FDA and, if criteria are met, may qualify the candidate for additional programs, including rolling review and priority review, which provide faster routes to approval.
“Aligos’ mission since its founding has been to improve outcomes for patients with unmet needs in liver and viral diseases, and being granted Fast Track Designation for pevifoscorvir sodium is the next step in our journey to make this a reality,” Lawrence Blatt, PhD, chairman, president, and CEO at Aligos, said in a company press release.
Aligos also announced data from the first prespecified interim analysis of the global Phase 2 B-SUPREME clinical trial (NCT06963710). The study is comparing pevifoscorvir sodium to the standard antiviral tenofovir disoproxil fumarate (sold as Viread, with generics available) in adults with chronic hepatitis B, regardless of their HBeAg status. HBeAg is a hepatitis B virus (HBV) protein that indicates the virus is replicating in the body.
Pevifoscorvir sodium, previously known as ALG-000184, has been well tolerated to date, with no safety concerns, according to the company. B-SUPREME’s independent Data Safety Monitoring Review Board (DSMB) has also recommended that the trial continue after futility criteria were not met, meaning that data so far suggest the treatment has the potential to be effective.
Still, the DSMB recommended increasing the number of patients in the HBeAg-negative group from the 74 currently enrolled to 100 to boost the trial’s ability to demonstrate a statistically significant effect. The company remains blinded to participant-level data.
“We are encouraged by this recommendation from the DSMB to increase the sample size in order to increase the probability for success of the study’s primary [goal],” Blatt said. “We believe we can enroll the necessary study participants in the coming months, with topline data on track for 2027.”
Pevifoscorvir sodium aims to achieve stronger HBV suppression
Hepatitis B refers to liver inflammation caused by an HBV infection. In most cases, the infection resolves on its own, but if it persists, it can lead to liver damage and liver cancer. Antiviral medications are currently used to stop viral DNA replication, but viral genetic material can still remain in the body.
Pevifoscorvir sodium is an oral drug that disrupts the protective shell around the genetic material of the virus, aiming to achieve stronger HBV suppression by blocking both DNA replication and the viral proteins needed for cell infection.
Results from a previous Phase 1 trial (NCT04536337) demonstrated that pevifoscorvir sodium, either alone or in combination with the approved antiviral therapy entecavir (sold as Baraclude, with generics available), consistently reduced HBV DNA levels in both HBeAg-positive and HBeAg-negative patients for up to 1.5 years.
The combo demonstrated a stronger antiviral response than entecavir alone in HBeAg-positive patients, with a favorable safety profile.
Interim analysis of trial finds no clinically significant abnormalities
B-SUPREME, which began dosing last year, was designed to enroll adults, ages 18-65, with chronic hepatitis B who have either never been treated or are not currently being treated for hepatitis B, and who may be positive or negative for HBeAg.
The first part recruited 103 HBeAg-positive participants and the second part has included 74 HBeAg-negative patients to date. Participants are randomly assigned to receive pevifoscorvir sodium or tenofovir disoproxil fumarate once daily for 48 weeks, or about one year.
For both study parts, the main goal is to determine the proportion of participants who achieve HBV DNA levels below the lower limit of quantification at 48 weeks. Secondary and exploratory measures will assess the therapy’s safety, pharmacological properties, and its effects on other disease-related biomarkers.
Participants who complete the one-year treatment will have the option to enter the trial’s open-label extension phase, during which all will receive pevifoscorvir sodium for 48 weeks.
The trial’s first prespecified interim analysis was conducted after about 60% of the 74 HBeAg-negative patients had been treated for at least 12 weeks, or about three months. Safety data for all 174 participants were also reviewed.
Results showed that the treatment was well tolerated with no clinically significant abnormalities identified across laboratory results, physical examinations, vital signs, or the heart’s electrical activity. No viral breakthroughs attributable to either therapy have been observed to date.
“As we progress the Phase 2 B-SUPREME study, we look forward to working with regulators to determine the appropriate path forward,” Blatt said.
