Bulevirtide

Unassigned

New Medicines

Hepcludex · Hepatitis D infection in adult patients with compensated liver disease

Information

Hepcludex
New molecular entity
MYR Pharma
MYR Pharma

Development and Regulatory status

Recommended for approval (Positive opinion)
Recommended for approval (Positive opinion)
Phase II Clinical Trials
Yes
Yes
May 20 · Recommended for conditional EU approval by CHMP - the full indication is "for the treatment of chronic hepatitis delta virus (HDV) infection in plasma (or serum) HDV-RNA positive adult patients with compensated liver disease." It is proposed that the medicine be prescribed by physicians experienced in the treatment of patients with HDV infection. [7] Conditional approval is given to medicines for which the public health benefit outweighs the risk of limited data availability. The manufacturer will normally be expected to provide further clinical data to gain full authorisation.
Nov 19 · Myr Pharmaceuticals is a German company, and currently has no UK presence, which may delay UK launch.
Nov 19 · MAA has been submitted for the indication ´ treatment of chronic hepatitis delta virus (HDV) infection in adult patients with compensated liver disease´ [3].
Oct 19 · Filed in EU under centralised procedure. Application is being reviewed under EMA´s accelerated assessment programme [2].
Mar 19 · MHRA granted PIM designation, in October 2018, the US FDA granted breakthrough therapy designation, in May 2017, bulevirtide was granted PRIME eligibility by the European Medicines Agency [1]

Category

Sodium-bile acid cotransporter inhibitor
Globally, its estimated that ~5% of HBsAg positive people are coinfected with HDV. High-prevalence areas include the Mediterranean, Middle East, Pakistan, Central and Northern Asia, Japan, Taiwan, Greenland and parts of Africa (mainly the horn of Africa and West Africa), the Amazon Basin and certain areas of the Pacific. Prevalence is low in North America and Northern Europe, South Africa, and Eastern Asia. (http://www.who.int/mediacentre/factsheets/hepatitis-d/en/)
Hepatitis D infection in adult patients with compensated liver disease
Subcutaneous injection

Further information

Yes
To be confirmed

Trial or other data

May 19 · PIIb open label, randomised trial initiated to evaluate safety and efficacy of bulevirtide (2-10mg/day) with weekly s.c injections of pegylated interferon alfa-2a, in ~175 pts in Russia, Moldova (and possibly France and Romania) with chronic hepatitis D (MYR-204; NCT03852433). The primary efficacy endpoint is sustained virological response 24 (SVR 24) defined as undetectable HDV RNA at week 24 after the scheduled end of treatment. The estimated primary completion date is Feb 2023. [5]
Mar 18 · The open label PIIb MYR-202 trial (n=120) in chronically co-infected hepatitis B virus and hepatitis D virus pts is complete. This demonstrated dose-dependent antiviral efficacy with improvements of biochemical activity and liver stiffness after 24 weeks. The primary endpoint (HDV RNA negativation or decrease by ≥2 log10 from baseline to Week 24) was reached by 46%, 47%, 77%, and 3% of pts of arms A (Myrcludex B 2mg/day s.c. + tenofovir), B (Myrcludex B 5mg/day s.c. + tenofovir), C (Myrcludex B 10mg/day s.c. + tenofovir) and D (tenofovir). Median HDV RNA declined by - 1.75 log, - 1.60 log, - 2.70 log and - 0.18 log and ALT normaliaation was achieved in 42.8%, 50%, 40% and 6.6% respectively. No significant changes in all arms were observed for HBsAg. Elevated conjugated bile salts were observed in pts treated with myrcludex B. Myrcludex B was well tolerated. Apart from bile acids increase, no specific AE pattern was observed except for temporary injection site reactions and lab abnormalities. Two SAEs led to study medication withdrawal. [4,6]
Mar 18 · PIIb MYR-202 trial completed which evaluated the efficacy and safety of bulevirtide in combination with tenofovir in chronically co-infected hepatitis B virus and hepatitis D virus patients. [1]
Apr 17 · Enrolment complete in the open label, randomised PIIb MYR-203 trial to evaluate efficacy and safety of bulevirtide + pegylated interferon alpha vs. pegylated interferon alpha alone in chronically hepatitis B virus (HBV)/hepatitis D virus (HBD) co-infected pts (MYR203; NCT02888106, n=90). The primary endpoint, improvement of the HDV RNA sustained virologic response (SVR) rates and improvement in HBsAg loss rates. Interim data showed declined serum HDV RNA levels in all Myrcludex B arms at week 48 (-4.59 log 10 IU/ml in B (n=15), -5.33 log 10 IU/ml in C (n=14), and -2.47 log 10 IU/ ml in D (n=14)). HDV RNA was reduced by 1.95 log 10 IU/ml by PEG-IFNα alone. HDV RNA was undetectable in 2/15 (A - PEG-IFNα once weekly), 10/15 (B - Myrcludex B 2 mg), 8/14 (C- Myrcludex B once daily plus PEG-IFNα) and 2/14 (D - Myrcludex B 5mg alone) pts at week 48. HBsAg changes were not observed under monotherapy. Myrcludex B was well tolerated with 155 drug related adverse events with 72 adverse events caused by increase in total bile salts which returned to baseline by week 50. Serious drug adverse events were not observed.[4]

Evidence based evaluations