Dive Brief:
- An RNA-based shot developed by GSK and Ionis Pharmaceuticals helped wipe out hepatitis B in about a fifth of the patients who received it in a pair of clinical trials, according to study results published Thursday in the New England Journal of Medicine.
- Called bepirovirsen, the shot could represent an important advance for people with chronic hepatitis B infections, less than 1% of whom can achieve such a “functional cure” with the help of oral antivirals. None of the participants who received a placebo hit that mark in the two trials presented Thursday.
- The Food and Drug Administration is already reviewing an approval application for bepirovirsen, and has granted the drug “fast track” and “breakthrough therapy” designations that could speed up its evaluation. An approval decision is expected no later than Oct. 26.
Dive Insight:
Bepirovirsen is poised to become an important part of GSK’s future. The drug is one of 15 the company highlighted in January as likely to generate more than $2 billion in peak sales in the years ahead. Its results were hailed by physicians at a medical meeting Thursday as a “historic moment” and a “huge leap forward” for patients, wrote Jefferies analyst Michael Leuchten in a client note.
Hepatitis B infections can be prevented with vaccination. But some 240 million people nonetheless have the kind of “chronic” infections that can fester and lead to serious health complications such as cirrhosis and liver cancer. About 1 million deaths are attributed to the disease each year, and the current treatments — like Gilead Sciences’ Vemlidy — have to be taken for life.
Bepirovirsen could change that. Whereas available therapies are antivirals that only stop the virus from replicating, GSK and Ionis’ treatment is an antisense oligonucleotide that prevents spreading while also stimulating an immune response. That dual mechanism is supposed to better help the body clear out infected cells, offering the chance at a longer-term, “functional cure.”
Ionis developed the therapy and licensed it to GSK in 2019. Since then, the partners have advanced it to the precipice of approval.
The two trials reported Thursday, B-Well 1 and B-Well 2, enrolled 981 and 857 people with chronic hepatitis B, respectively. Two thirds were randomized to receive bepirovirsen on top of antivirals, with the remainder getting those antivirals and a placebo. Patients who got bepirovirsen were treated for 24 weeks. After 48 weeks, enrollees with undetectable disease were taken off their standard medications, too.
In B-Well 1 and B-Well 2, 20% and 19% of bepirovirsen recipients achieved a functional cure compared to none of those in the placebo arms. The cure rates were higher in people who entered the trial with lower levels of a key viral protein, with 25% hitting that mark in B-Well 1 and 28% in B-Well 2.
Trial enrolles receiving bepirovirsen reported more side effects, although only a small percentage discontinued or interrupted doses. Injection site reactions were the most common adverse event reported, though liver enzyme elevations were also detected.
“With recent guidelines now prioritizing functional cure, these new data could represent an important advance,” said trial investigator Jinlin Hou, director of the Guangdong Institute of Hepatology in China, in a statement provided by GSK. “Combined with improved testing and diagnosis, this innovation has the potential to improve the lives of millions living with [chronic hepatitis B].”
According to Leuchten, of Jefferies, the findings position GSK and Ionis’ drug as the “key backbone for combination strategies” and support “clear blockbuster potential.”
“We see this data as likely to meaningfully shift the HBV treatment paradigm, particularly for patients who are already on therapy,” he wrote in that client note.
Meanwhile, Leerink Partners analyst Mani Foroohar wrote that bepirovirsen may be an “under-appreciated blockbuster potential in the long term,” but cautioned that screening, monitoring and physician office capacity could lead to a slower-than-usual launch trajectory.
