Bulevirtide adherence remains >90% for three years in chronic hepatitis D, improving virological response.
Background
Chronic hepatitis D (CHD) is the most severe form of viral hepatitis, leading to rapid progression of liver disease, cirrhosis, and hepatocellular carcinoma. Historically, treatment options have been limited and often ineffective, leaving a significant unmet medical need. Bulevirtide (BLV) is a first-in-class viral entry inhibitor targeting the sodium taurocholate cotransporting polypeptide (NTCP), preventing HDV entry into hepatocytes. While approved, real-world data on long-term adherence and its impact on treatment outcomes have been scarce.
Study Design
The HERACLIS_BLV_D study (NCT05928000) was an observational cohort study including 76 adult patients with chronic hepatitis D initiating Bulevirtide 2 mg/day via subcutaneous injection. Patients were followed in routine clinical practice, with adherence assessed through a national prescription system based on executed monthly prescriptions. Treatment discontinuation was defined as no executed prescription for >3 months. Primary endpoints included virological response (VR), defined as HDV RNA <57.5 IU/mL or decline >2 log10, and biochemical response (BR), defined as normal ALT (≤40 IU/L).
Results
Adherence to Bulevirtide therapy was excellent, averaging 98% ± 6% in the first year, gradually declining to 93% ± 13% in the second year and 91% ± 17% in the third year (p ≤ 0.010). Only 13 (17%) patients discontinued BLV, with an annual discontinuation rate of 6%-7%, and notably, none due to adverse events. Virological response rates were 73% at 12 months and improved to 93% at 24 months, while biochemical response rates were 71% and 74% respectively. No baseline characteristic predicted poor (<90%) or good (≥90%) adherence. However, adherence significantly impacted outcomes:
Patients with poor (<90%) adherence had substantially lower virological response rates compared to those with good (≥90%) adherence: 33% vs. 77% in the first year (p = 0.038), and 60% vs. 97% in the second year (p = 0.030).
Key Findings
- Mean Bulevirtide adherence was 98% ± 6% in the 1st year, declining to 91% ± 17% by the 3rd year (p ≤ 0.010).
- Only 17% of patients discontinued Bulevirtide, with no discontinuations due to adverse events.
- Virological response rates reached 73% at 12 months and 93% at 24 months.
- Patients with poor (<90%) adherence had significantly lower VR rates (33% vs. 77% at 1 year, p = 0.038) compared to good adherence.
Why It Matters
This real-world data confirms that Bulevirtide therapy for chronic hepatitis D demonstrates high adherence rates, remaining above 90% for up to three years, which is crucial for a chronic condition requiring long-term treatment. The strong correlation between adherence and virological response underscores that consistent Bulevirtide use is paramount for achieving optimal viral suppression and preventing disease progression. For clinicians and patients, this emphasizes the importance of patient education and support strategies to maintain adherence, especially as it gradually declines over time. The low discontinuation rate due to adverse events also reinforces its favorable safety profile in real-world settings, making it a viable long-term option.
bulevirtide
chronic-hepatitis-d
hdv
adherence
real-world
cohort-study