Meeting News

Myrcludex B with tenofovir shows response in HDV/HBV coinfection

PARIS — Adding myrcludex B to existing tenofovir treatment in patients with hepatitis delta and hepatitis B coinfection led to virologic response and biochemical improvement, according to a presentation at the International Liver Congress 2018.

“We have learned in recent years that HDV RNA reduction or suppression even in the presence of HBS antigen is associated with an improved clinical long-term outcome,” Heiner Wedemeyer, MD, chairman of the department of gastroenterology and hepatology at the University Clinic Essen, said during his presentation. “Blocking HBV/HDV entry with myrcludex B (MYR Pharma) is a safe and promising strategy to treat chronic hepatitis delta. The optimal treatment durations and possible combination therapies need to be determined and ... cries for longer therapy. We performed modeling studies suggesting 2 to 3 years should be sufficient to reduce HDV RNA levels to undetectable.”

Wedemeyer presented data from the multicenter, open-label phase 2b trial to assess efficacy and safety of myrcludex B in patients already treated with tenofovir, looking specifically at its antiviral efficacy against and optimal dose in HDV. In this study, investigators randomly assigned 120 patients who were all pretreated with tenofovir for at least 12 weeks to either no myrcludex B or 2 mg, 5 mg or 10 mg of myrcludex B. Tenofovir dosing was maintained for all groups. Myrcludex B was injected for 24 weeks and patients were followed out to 48 weeks.

As myrcludex B blocks the bile acid transporter NTCP, an increase in bile acids was expected, Wedemeyer said. At week 24, asymptomatic increases were seen in each group: 50% increase in the 2 mg group; 74% increase in the 5 mg group; 91% increase in the 10 mg group; and a 19% increase in the tenofovir control group.

“This was immediate onset within a day. This was dose-dependent and when you stop myrcludex, baseline levels were reached, which was quite remarkable,” Wedemeyer said. “I have to highlight that despite the increase in bile acids, there was no patient reported itching. Increase in bile acids, per se, does not cause itching.”

Despite these increases, no serious adverse events were reported as related to myrcludex B during the trial and no participants discontinued due to the medication. Wedemeyer did report a post-treatment increase in ALT in 12 of the 90 patients dosed with myrcludex B, but there was no worsening of liver function and no jaundice, he said.

With a primary endpoint of 2 log HDV RNA decline or undetectable RNA at week 24, Wedemeyer reported that effect in 46.4% of the 2-mg group, 46.8% of the 5-mg group and 76.6% of the 10-mg group (all P < .001 vs. the 3.3% in the tenofovir group who achieved the same).

The median log change from baseline at week 24 was –1.75 for the 2 mg group, –1.6 in the 5 mg group and –2.7 in the 10 mg group, Wedemeyer said.

“Importantly, this virological response correlated very well also with an intrahepatic decline in HDV,” he added, showing the linear decline. In contrast, the biophysical response showed a biphasic decline, he said. “There was correlation between biochemical response and HDV decline during therapy. ... More importantly, this biochemical improvement also translated to other parameters, which improved like Fibroscan levels.”

In conclusion, Wedemeyer said, “Myrcludex B therapy was safe and very well tolerated in tenofovir-treated patients with chronic hepatitis D.”

For more information:

Wedemeyer H, et al. GS-005 Presented at: International Liver Congress; Apr. 11-15, 2018; Paris, France.

Disclosure: This study was supported by Hepatera LLC and MYR GmbH. Gilead Sciences provided the medications used. Wedemeyer reports no relevant financial relationships.

PARIS — Adding myrcludex B to existing tenofovir treatment in patients with hepatitis delta and hepatitis B coinfection led to virologic response and biochemical improvement, according to a presentation at the International Liver Congress 2018.

“We have learned in recent years that HDV RNA reduction or suppression even in the presence of HBS antigen is associated with an improved clinical long-term outcome,” Heiner Wedemeyer, MD, chairman of the department of gastroenterology and hepatology at the University Clinic Essen, said during his presentation. “Blocking HBV/HDV entry with myrcludex B (MYR Pharma) is a safe and promising strategy to treat chronic hepatitis delta. The optimal treatment durations and possible combination therapies need to be determined and ... cries for longer therapy. We performed modeling studies suggesting 2 to 3 years should be sufficient to reduce HDV RNA levels to undetectable.”

Wedemeyer presented data from the multicenter, open-label phase 2b trial to assess efficacy and safety of myrcludex B in patients already treated with tenofovir, looking specifically at its antiviral efficacy against and optimal dose in HDV. In this study, investigators randomly assigned 120 patients who were all pretreated with tenofovir for at least 12 weeks to either no myrcludex B or 2 mg, 5 mg or 10 mg of myrcludex B. Tenofovir dosing was maintained for all groups. Myrcludex B was injected for 24 weeks and patients were followed out to 48 weeks.

As myrcludex B blocks the bile acid transporter NTCP, an increase in bile acids was expected, Wedemeyer said. At week 24, asymptomatic increases were seen in each group: 50% increase in the 2 mg group; 74% increase in the 5 mg group; 91% increase in the 10 mg group; and a 19% increase in the tenofovir control group.

“This was immediate onset within a day. This was dose-dependent and when you stop myrcludex, baseline levels were reached, which was quite remarkable,” Wedemeyer said. “I have to highlight that despite the increase in bile acids, there was no patient reported itching. Increase in bile acids, per se, does not cause itching.”

Despite these increases, no serious adverse events were reported as related to myrcludex B during the trial and no participants discontinued due to the medication. Wedemeyer did report a post-treatment increase in ALT in 12 of the 90 patients dosed with myrcludex B, but there was no worsening of liver function and no jaundice, he said.

With a primary endpoint of 2 log HDV RNA decline or undetectable RNA at week 24, Wedemeyer reported that effect in 46.4% of the 2-mg group, 46.8% of the 5-mg group and 76.6% of the 10-mg group (all P < .001 vs. the 3.3% in the tenofovir group who achieved the same).

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The median log change from baseline at week 24 was –1.75 for the 2 mg group, –1.6 in the 5 mg group and –2.7 in the 10 mg group, Wedemeyer said.

“Importantly, this virological response correlated very well also with an intrahepatic decline in HDV,” he added, showing the linear decline. In contrast, the biophysical response showed a biphasic decline, he said. “There was correlation between biochemical response and HDV decline during therapy. ... More importantly, this biochemical improvement also translated to other parameters, which improved like Fibroscan levels.”

In conclusion, Wedemeyer said, “Myrcludex B therapy was safe and very well tolerated in tenofovir-treated patients with chronic hepatitis D.”

For more information:

Wedemeyer H, et al. GS-005 Presented at: International Liver Congress; Apr. 11-15, 2018; Paris, France.

Disclosure: This study was supported by Hepatera LLC and MYR GmbH. Gilead Sciences provided the medications used. Wedemeyer reports no relevant financial relationships.

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