Regulatory Decision Summary for GALEXOS

Health Canada considers that the benefits of Galexos in combination with other medicinal products for the treatment of genotype 4 chronic hepatitis C (CHC) in adults with compensated liver disease outweigh the potential risks.

This submission included an open-label, single-arm, Phase III study to evaluate results of the efficacy, safety and tolerability of Galexos in combination with peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) in subtreatment-naïve or treatment-experienced, CHC virus genotype-4 infected patients. Patients were treated with Galexos 150 mg administered once-daily for 12 weeks in combination with PegIFNα-2a /RBV. Treatment-naïve patients and prior relapsers received PegIFNα-2a /RBV for response guided treatment (RGT) duration of 24 or 48 weeks. All other patients received PegIFNα-2a /RBV for 48 weeks. Sustained virologic response (SVR) at week 12 (SVR12) was achieved in 82.9% (29/35), 86.4% (19/22), 60.0% (6/10) and 40.0% (16/40) of the treatment-naïve, prior relapser, prior partial-responder, and prior null-responder patients, respectively. The majority of the treatment-naïve and prior relapse patients met the RGT criteria for a shortened PegIFNα-2a /RBV treatment duration of 24 weeks.

New analyses support a total treatment duration of 24 weeks (12 weeks of Galexos + 24 weeks of PegIFNα-2a /RBV) in HCV genotype-1 and genotype-4 treatment-naïve and prior relapser patients with or without cirrhosis who are not co-infected with human immunodeficiency virus (HIV) and those without cirrhosis who are co-infected with HIV. A total treatment duration of 48 weeks (12 weeks of Galexos + 36 weeks of PegIFNα-2a /RBV) is recommended for (1) HCV genotype 1 and genotype 4 infected treatment-naïve and prior relapser patients with cirrhosis who are co-infected with HIV and (2) prior partial and null responders with HCV genotype 1, with or without cirrhosis, with or without HIV co-infection.

Testing for Q80K polymorphism is recommended in HCV genotype-1a infected patients to be treated with Galexos + Q80K /RBV based on the results of the study. In the absence of Q80K information, the general treatment recommendations and treatment stopping rules apply.

Overall, 23.4% (25/107) of patients experienced on-treatment failure. By prior HCV treatment response, most on-treatment failures were observed in prior null-responders (45.0%, 18/40), compared with treatment-naïve (8.6%, 3/35), prior relapsers (9.1%, 2/22), and prior partial-responders (20.0%, 2/10).

The baseline Q80K polymorphismwas not observed among HCV GT4 infected patients at baseline.

With regard to safety, most patients had ≥1 Adverse Events (AE) (98.1%) during the Galexos + PegIFN/RBV treatment phase. The most frequent AEs were influenza-like illness (45.8%), asthenia (42.1%), and fatigue (34.6%). The majority of adverse events (AEs) were grade 1 or 2 (91.6%). Grade 3 or 4 AEs were reported in 6.5% of patients. All grade 3 or 4 AEs were reported in <3% of patients. No patients died during the study. Serious AEs were reported in 5 (4.7%) patients, all of which were considered not or doubtfully related to Galexos by the investigator.

Two serious AEs (diabetes mellitus and anemia) were considered probably related to PegIFNα-2a and RBV. Galexos and RBV were discontinued due to an AE (overdose) in 1 (0.9%) subject. Peginterferon alfa-2a was also discontinued due to an AE (bradycardia) in this subject.

Some AEs were defined as AEs of special interest (increased bilirubin) or of clinical interest [rash (any type), pruritus, anemia, photosensitivity conditions, neutropenia, and dyspnea]. Almost all of these events were grade 1 or 2. The only grade 3 or 4 AEs of interest were neutropenia and anemia, reported in 2 and 1 subject(s), respectively. Adverse events of interest were reported as serious in 1 subject (anemia).

The overall safety results from the final analyses of these studies are similar to the previously established safety profile of Galexos. No new safety concerns were identified.

A review of the presented information indicated that the overall benefit-risk assessment is favorable for the use of Galexos in the treatment of genotype 4 CHC in combination with PegINFα-2a and RBV, in adults with compensated liver disease.