The hepatitis D drug bulevirtide from Gilead Sciences has been approved by the FDA – three years after initially being rejected because of manufacturing and delivery concerns, reports Fierce Pharma.
The green light was given last week to Hepcludex as the first treatment for chronic hepatitis D virus infection in the United States, granting the entry inhibitor an accelerated approval in adults without cirrhosis or with compensated cirrhosis – a complication of long-term liver inflammation that leads to progressive scarring of the organ.
The therapy clearance was based on data from Gilead’s late-stage MYR301 study, in which Hepcludex helped patients achieve statistically significant improvements in a combined virologic and biochemical response at 48 weeks versus a control group that received delayed treatment, the company said in a release.
But Gilead caveated that improvement in disease-related clinical outcomes “has not been established” in its body of evidence for Hepcludex. Given the accelerated nature of the regulator’s nod, the company will more than likely need to confirm the drug’s benefit in a confirmatory trial.
MYR301’s primary endpoint looked at combined response, defined as undetectable hepatitis D virus RNA and aminotransferase normalisation at the 48-week mark. Patients in the Hepcludex arm achieved a combined response rate of 48% versus a slim 2% in the delayed treatment arm, per the FDA’s approval announcement.
When Gilead first touted its Hepcludex phase 3 win in 2022, the company stressed its confidence in the therapy as a potential monotherapy for chronic hepatitis D treatment in the US.
The drug, which won a conditional nod in the European Union in 2020 before scoring full approval there in 2023, was a central pillar of Gilead’s €1.15bn buyout of German biotech MYR in late 2020, with the California-based company aiming to swiftly accelerate the hepatitis treatment’s launch overseas as a US verdict loomed.
But the drug landed a surprise US rejection in 2022, when the FDA denied Gilead’s application on the grounds that it had manufacturing and delivery concerns with the treatment.
Gilead did not disclose the nature of the issue at the time.
Chronic hepatitis D infection represents the most severe form of viral hepatitis and is linked to a “markedly higher risk” of quick disease progression, liver failure and mortality versus hepatitis B alone, according to Gilead. It’s estimated that in America, around 2% to 4% of people who have chronic hepatitis B – or about 40 000 to 80 000 people – are also affected by the delta pathogen.
While Gilead has not publicised the reasons behind its initial US rejection, the company faced a separate regulatory headache tied to manufacturing and delivery around late 2021, when 10 of its studies on the HIV med lenacapavir, now approved as the ultra-long-acting PrEP drug Yeztugo, which recently landed in South Africa, and HIV treatment Sunlenca, were put on hold over concerns that the drug solution was incompatible with the borosilicate vials in which it was stored, leading to the potential for “sub-visible” glass particles to shed into the medication.
In May the next year, Gilead escaped the FDA’s hold by proposing to use a different vial for lenacapavir made from aluminosilicate glass, though not before facing a rejection from the regulator.
See more from MedicalBrief archives:
Demand for new HIV jab outstrips supply in African rollout
Gilead wins hepatitis drug patent infringement case
FDA approves new single tablet ARV from Gilead but ViiV Healthcare sues