The following adverse reactions are discussed in other sections of the labeling: Exacerbation of Hepatitis D and B After Discontinuation of Treatment [see Warnings and Precautions (5.1) ]. The most common adverse reactions (incidence greater than or equal to 10%, all grades) observed with treatment with HEPCLUDEX are injection site reactions, headache, abdominal pain, fatigue, and pruritus . ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The overall safety profile of HEPCLUDEX is based on Phase 2 and Phase 3 data from 165 adults with chronic HDV infection without cirrhosis or with compensated cirrhosis who received at least 48 weeks of HEPCLUDEX 8.5 mg subcutaneous injection once daily.
Trial MYR301 was a Phase 3 randomized, multi-center, open-label, parallel-arm trial in 101 adults. In this trial, 50 adults received 8.5 mg HEPCLUDEX daily for 144 weeks and 51 adults who were in the Delayed Treatment group received no HDV treatment for the first 48 weeks; 50 adults in the Delayed Treatment group then received HEPCLUDEX 8.5 mg once daily for 96 weeks [see Clinical Studies (14) ]. Table 1 displays the frequency of the adverse reactions (all grades) ≥ 10% in the HEPCLUDEX group at Week 48.
No participant discontinued treatment with HEPCLUDEX due to an adverse reaction through Week 48. Table 1 Adverse Reactions Frequencies of adverse reactions are based on all treatment-emergent adverse events, regardless of relationship to study drug. (All Grades) Reported in ≥ 10% of Participants with Chronic HDV Infection Without Cirrhosis or With Compensated Cirrhosis Receiving HEPCLUDEX in Trial MYR301 (Week 48 Analysis) Adverse Reaction HEPCLUDEX (N=50) Delayed Treatment Participants who received no HDV treatment in Trial MYR301 for the first 48 weeks.
(N=51) Injection site reactions Grouped term includes injection site abscess, injection site erythema, injection site reaction, injection site pruritus, injection site swelling, injection site hematoma, injection site rash, injection site dermatitis, and injection site pain. 30% 0 Headache 20% 0 Abdominal pain Grouped term includes abdominal pain, abdominal pain lower, and abdominal pain upper. 18% 2% Fatigue 14% 2% Pruritus 14% 0 A similar safety profile was observed through Week 144 in Trial MYR301 and for participants in the Delayed Treatment group who switched to treatment with HEPCLUDEX at Week 48 through to Week 144.
Additionally, a similar safety profile was observed through Week 96 in Phase 2b Trial MYR204. Laboratory Abnormalities Eosinophil Count Increased: In MYR301, increases in eosinophil counts were reported in 33% of participants (all Grade 1) receiving HEPCLUDEX; there were no associated clinical sequelae, hepatic adverse reactions, or significant liver-related laboratory abnormalities. Total Bile Salts Increased: HEPCLUDEX inhibits sodium taurocholate co-transporting polypeptide (NTCP)-mediated bile acid transport.
Consistent with this, elevations in total serum bile salt levels were observed in clinical trials of HEPCLUDEX. In MYR301, all participants who received HEPCLUDEX had elevated serum bile salts. Bile salt levels showed visit-to-visit variability and peaked by Week 8 of treatment in both participants without cirrhosis and those with compensated cirrhosis, although median levels trended higher in the latter group. Bile salt elevations resolved upon discontinuation of HEPCLUDEX.
In MYR301, 14% of HEPCLUDEX recipients experienced Grade 1 or 2 pruritus that was self-limited. The magnitude of total serum bile salt elevations did not correlate with the severity of pruritus.
