Meeting News

Combo therapy nears ‘curative’ levels in HBV/HDV coinfection

VIENNA — A combination of Myrcludex with interferon produced undetectable levels of hepatitis D and significant lowering of hepatitis B virus, according to data presented during the International Liver Congress 2019.

“This is by far the best data we have ever seen for HDV infection,” Heiner Wedemeyer, MD, chairman of the department of gastroenterology and hepatology at the University Clinic Essen, said during a press conference. “In some patients, this combination therapy may have also curative potential for hepatitis B virus infection.”

Wedemeyer presented the phase 2b trial in which patients were randomized into four treatment groups: weekly pegylated interferon alpha (PEG-IFN; n = 15); 2 mg daily Myrcludex (bulevirtide, MYR Pharma) subcutaneous injection with weekly PEG-IFN (n = 15); 5 mg daily myrcludex with weekly PEG-IFN (n = 15); or 2 mg daily bulevirtide subcutaneous injections as monotherapy (n = 15). The researchers followed the patients for 24 weeks after 48 weeks of treatment.

At 48 weeks, Wedemeyer reported PEG-IFN monotherapy brought HDV RNA log reduction of –1.3 with alanine aminotransferase normalization in 27% of patients. The combination groups had a median HDV RNA log reduction between –4.81 and –5.59 with 37% of patients normalizing ALT. Bulevirtide monotherapy lowered HDV RNA log by –2.84 and normalized ALT in 67% of patients.

“Not surprisingly we had a rebound after the end of therapy,” Wedermeyer said. “This ... cries for longer therapy and this is what is currently developing in the phase 3 studies.”

The primary endpoint was undetectable HDV RNA, which Wedemeyer reported occurred in 13% of PEG-IFN monotherapy patients, 13% of bulevirtide monotherapy patients and 50% of patients receiving combination treatment.

“You can see not only an additive response, but we found a decline of HDV RNA and many patients stayed HDV RNA negative 24 weeks after the end of therapy,” Wedermeyer said. “This is undetectable with the most sensitive assay we have.”

After follow-up, at week 72, Wedermeyer reported that PEG-IFN monotherapy saw a reduction of –0.26 in HDV RNA log and 7% normalization of ALT. Combination therapies had a median HDV RNA log reduction between –1.48 and –4.04 and 40% normalization of ALT. Bulevirtide monotherapy had a median HDV RNA log reduction of –1.08 and normalization of ALT in 20% of patients.

In that longer follow-up, combination therapy left 40% of patients with undetectable HDV and, surprisingly, 27% of patients who received 2 mg bulevirtide with PEG-IFN had undetectable HBsAg levels while three-quarters of the patients had HBsAg seroconversion.

“If you block entry of virulent, both [hepatitis] B and D, combined with interferon ... we saw these patients had a profound decline of S antigen, which is basically the main indicator of hepatitis B virus,” Wedemeyer said. “The functional cure with this combination therapy was possible and reached more than 25%, which is again the best we have seen so far with any of the modern therapies.”

Wedermeyer said there were no serious adverse events related to bulevirtide during the study, though they did see an asymptomatic increase in bile salts in the combination therapy cohorts, with the majority of adverse events related to the combination treatment. He added that phase 3 studies will concentrate on bulevirtide 2 mg and 10 mg.

“In the long term, the drug is developed ... currently as a monotherapy for severe patients but for those patients that may tolerate interferon, combination therapy maybe has curative potential for the first time for HDV infection,” Wedemeyer said. – by Katrina Altersitz

Reference:

Wedemeyer H. GS-13. Presented at: International Liver Congress; April 10-14, 2019; Vienna, Austria.

Disclosures: Wedemeyer reports receiving honoraria for consulting or speaking and/or research grants from Abbott, AbbVie, BMS, Boehringer Ingelheim, Eiger, Gilead, JJ/Janssen-Cilag, Merck/Schering-Plough, Myr GmbH, Novartis, Roche, Roche Diagnostics and Siemens.

VIENNA — A combination of Myrcludex with interferon produced undetectable levels of hepatitis D and significant lowering of hepatitis B virus, according to data presented during the International Liver Congress 2019.

“This is by far the best data we have ever seen for HDV infection,” Heiner Wedemeyer, MD, chairman of the department of gastroenterology and hepatology at the University Clinic Essen, said during a press conference. “In some patients, this combination therapy may have also curative potential for hepatitis B virus infection.”

Wedemeyer presented the phase 2b trial in which patients were randomized into four treatment groups: weekly pegylated interferon alpha (PEG-IFN; n = 15); 2 mg daily Myrcludex (bulevirtide, MYR Pharma) subcutaneous injection with weekly PEG-IFN (n = 15); 5 mg daily myrcludex with weekly PEG-IFN (n = 15); or 2 mg daily bulevirtide subcutaneous injections as monotherapy (n = 15). The researchers followed the patients for 24 weeks after 48 weeks of treatment.

At 48 weeks, Wedemeyer reported PEG-IFN monotherapy brought HDV RNA log reduction of –1.3 with alanine aminotransferase normalization in 27% of patients. The combination groups had a median HDV RNA log reduction between –4.81 and –5.59 with 37% of patients normalizing ALT. Bulevirtide monotherapy lowered HDV RNA log by –2.84 and normalized ALT in 67% of patients.

“Not surprisingly we had a rebound after the end of therapy,” Wedermeyer said. “This ... cries for longer therapy and this is what is currently developing in the phase 3 studies.”

The primary endpoint was undetectable HDV RNA, which Wedemeyer reported occurred in 13% of PEG-IFN monotherapy patients, 13% of bulevirtide monotherapy patients and 50% of patients receiving combination treatment.

“You can see not only an additive response, but we found a decline of HDV RNA and many patients stayed HDV RNA negative 24 weeks after the end of therapy,” Wedermeyer said. “This is undetectable with the most sensitive assay we have.”

After follow-up, at week 72, Wedermeyer reported that PEG-IFN monotherapy saw a reduction of –0.26 in HDV RNA log and 7% normalization of ALT. Combination therapies had a median HDV RNA log reduction between –1.48 and –4.04 and 40% normalization of ALT. Bulevirtide monotherapy had a median HDV RNA log reduction of –1.08 and normalization of ALT in 20% of patients.

In that longer follow-up, combination therapy left 40% of patients with undetectable HDV and, surprisingly, 27% of patients who received 2 mg bulevirtide with PEG-IFN had undetectable HBsAg levels while three-quarters of the patients had HBsAg seroconversion.

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“If you block entry of virulent, both [hepatitis] B and D, combined with interferon ... we saw these patients had a profound decline of S antigen, which is basically the main indicator of hepatitis B virus,” Wedemeyer said. “The functional cure with this combination therapy was possible and reached more than 25%, which is again the best we have seen so far with any of the modern therapies.”

Wedermeyer said there were no serious adverse events related to bulevirtide during the study, though they did see an asymptomatic increase in bile salts in the combination therapy cohorts, with the majority of adverse events related to the combination treatment. He added that phase 3 studies will concentrate on bulevirtide 2 mg and 10 mg.

“In the long term, the drug is developed ... currently as a monotherapy for severe patients but for those patients that may tolerate interferon, combination therapy maybe has curative potential for the first time for HDV infection,” Wedemeyer said. – by Katrina Altersitz

Reference:

Wedemeyer H. GS-13. Presented at: International Liver Congress; April 10-14, 2019; Vienna, Austria.

Disclosures: Wedemeyer reports receiving honoraria for consulting or speaking and/or research grants from Abbott, AbbVie, BMS, Boehringer Ingelheim, Eiger, Gilead, JJ/Janssen-Cilag, Merck/Schering-Plough, Myr GmbH, Novartis, Roche, Roche Diagnostics and Siemens.

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