Key results
The primary endpoint was defined as a combination of decreased HDV RNA (defined as undetectable or a 2 log or greater decrease) and normalized ALT (defined as 3.1 U/L or less in women and 4.1 U/L or less in men). This was assessed after 48 weeks’ treatment and was achieved by 45% of participants given the 2-mg dose of bulevirtide, 48% of those given the 10-mg dose, and by 2% of those who had delayed treatment (P < .0001 for both doses, compared with delayed treatment).
The treatment benefit was consistent across all subgroups of patients, including those with cirrhosis, Dr. Wedemeyer reported.
Looking at some of the secondary endpoints, he reported that, when considering only decreased HDV RNA, the rate of response was over 70% with both dose of bulevirtide at week 48, compared with just 4% for delayed treatment (P < .0001), although there was no significant difference in rates of undetectable HDV RNA between the two doses. ALT normalization rates were 51%-56% versus 12% for delayed treatment (P < .0001).
A further benefit was seen in liver stiffness, with values reduced by at least three points at week 48 with either dose of bulevirtide, compared with an increase of almost 1 point for delayed treatment.
Dr. Thomas Berg
As for side effects, one of the concerns for bulevirtide is an increase in serum bile acids, but when this occurred, it occurred early and remained steady over the course of treatment, with a less pronounced effect in the 2 mg–dosed group than the 10 mg–dosed group. There were no serious adverse reactions related to bulevirtide or any adverse event that led to stopping the drug.
“There are always questions that need to be answered,” Dr. Wedemeyer acknowledged. Indeed, it’s unclear for how long patients need to be treated and if treatment with interferon is needed. In the phase 2 studies (MYR202 and MYR203), bulevirtide was given at the same time as pegylated interferon alpha (peg-IFNa) or tenofovir, whereas in the phase 3 MYR301 trial, it was given as monotherapy.
Real-world experience
“We have already some real-world data in parallel to this phase 3 trial,” Dr. Wedemeyer said. “So, for us in the hepatitis D field, it is a really exciting time; [it’s] completely novel data and game-changing for patients.”
“The results are similar to our real life study, but in our real-life study, we have some patients treated with interferon and some not treated with interferon,” Hélène Fontaine, MD, of Hôpital Cochin in Paris, observed in an interview.
She reported preliminary results from the prospective BuleDelta cohort, which showed a virologic response rate of 58% and ALT normalization in 46% of patients.
“Virologic response was achieved in more patients receiving bulevirtide in combination with interferon,” she said. Indeed, 84% of patient who received peg-IFNa versus 39% of those who did not achieved a virologic response. However, rates of ALT normalization were more frequent in those received bulevirtide monotherapy than in combination with peg-IFN1 (54% vs. 35%).
A greater benefit of combining bulevirtide with interferon therapy was also seen in another real-world study presented by Victor de Lédinghen, MD, PhD, of Bordeaux (France) University Hospital. After 18 months of treatment, bulevirtide plus peg-IFNa was associated with undetectable HDV RNA in 57% of patients versus 33% of those given the drug as monotherapy.
“Of course, if you add interferon, it’s better than without but you cannot use interferon in all patients,” he observed in an interview.
Results are good but could be better, he suggested, noting that the results are dependent on patients injecting themselves correctly on a daily basis.
At the media briefing Dr. Wedemeyer also commented on how bulevirtide must be delivered.
“The only, let’s say, disadvantage is that it has to be injected because it’s a peptide, which requires daily injections, but patients managed very well,” Dr. Wedemeyer said.
“There is some evidence from single cases that we may stop treatment and that the virus does not come back,” he said, but stressed that patients should not stop treatment on their own as the risk is not known.
“For patients with advanced disease I consider this as a maintenance treatment,” Dr. Wedemeyer said, at least for the time being.
The MYR3201 study was funded by Gilead Sciences. The BuleDelta cohort is sponsored by the ANRS Maladies Infectieuses Emergencies. Dr. Wedemeyer acknowledged research funding, acting as a consultant to, and giving paid lectures on behalf of Gilead Sciences and MYR as well as having ties to multiple pharmaceutical and biotechnology companies. Dr. Berg, Dr. Fontaine, and Dr. de Lédinghen had no conflicts of interest to report.