Sunvepra (generic name asunaprevir), developed by Bristol-Myers Sqibb, passed its Common Drug Review with the release of the Canadian Drug Expert Committee (CDEC) Final Recommendation for it.
The Canadian Drug Expert Committee Final Recommendation is important within the Canadian drug approval process as it’s sent to the provinces and territories to help them decide on how they want to cover the treatment through their PharmaCare plans.
The CDEC Final Recommendation for Sunvepra (asunaprevir) when combined with Daklinza (daclatasvir)
The CDEC advocates that Sunvepra, in combination with Daklinza (daclatasvir), be listed by drug plans as a treatment for adults with chronic hepatitis C genotype 1b and with Daklinza, pegylated interferon, and ribavirin, for patients with hep C genotype 1 or 4, if the following criteria/conditions are met:
Recommended Clinical Criteria
- None listed. This is the first CDEC report for a hep C treatment to not recommend that the treatment only be covered for patients who have a liver fibrosis stage of F2 or higher–this is a great omission.
Reasons for the Above Sunvepra Recommendations
A review of clinical trial results suggests that Sunvepra’s treatment response rates are comparable to success/cure rates of other interferon-free hep C treatments. However, it was noted that there are no trial results with direct comparisons to other treatments already covered by public drug programs. This has also been noted in CDEC recommendations for other hep C treatments.
“There is uncertainty regarding the cost-effectiveness of ASV [Sunvepra] combination regimens…” when they are compared with other hepatitis C treatments.(CDEC)
Noted Discussion Points
- Efficacy of these Sunvepra-based treatment combinations for patients with decompensated liver disease, hepatitis B, or HIV coinfection, malignancy, or recent drug use, remains uncertain. However, the current data indicates that Daklinza + Sunvepra is effective and safe for all of these patients.
- The CDEC believes that there will be “limited use” of pegylated interferon with ribavirin-based treatments when there are interferon-free treatments available.
Further research into patients infected with hepatitis C with L31 or Y93 HCV NS5A-resistant variant at baseline is needed. (CDEC)
The Canadian Drug Expert Committee’s Final Recommendation for Sunvepra can be found here.
Sunvepra (asunaprevir) is prescribed with other hepatitis C treatments/direct-acting antivirals (DAAs). It is a treatment for patients with chronic hepatitis C genotype 1 or 4.
Sunvepra, in combination with Daklinza, peginterferon, and ribavirin, has been tested on those with hep C genotype 1 or 4 who were non-responders (patients who tried treatment but it failed to achieve SVR/a cure) with great results. The cure rate when treating patients with hep C genotype 1 is 93.2%. The cure rate when treating patients with hep C genotype 4 is 100%. (Health Canada)
Lastly, doctors are able to prescribe Sunvepra to patients, but the hepatitis C treatment isn’t covered by PharmaCare yet.
“All patients with CHC [a chronic hepatitis C] infection should be considered for treatment, regardless of fibrosis score. Given the potential impact on health system sustainability of treating all patients with CHC infection on a first-come basis, priority for treatment should be given to patients with more severe disease.” (CADTH Canadian Drug Expert Committee, page 2, May 18, 2016)
Updated CADTH Canadian Drug Expert Committee Recommendations
The Canadian Drug Expert Committee (CDEC) updated their recommendations for the hep C treatments: Harvoni, Holkira Pak, Sovaldi, and Daklinza. They now recommend that the liver fibrosis stage F2 or greater requirement for treatment through PharmaCare should be removed. Where once their clinical criteria for treatment with Harvoni, for example, read, “Patients must have a liver fibrosis stage of F2 or greater before they are eligible for PharmaCare coverage“, the same report sections for Harvoni now read:
CDEC recommends that ledipasvir/sofosbuvir (LDV/SOF) be reimbursed for the treatment of chronic hepatitis C virus (CHC) genotype 1 infection in adults, if the following conditions are met.
- Treatment should be initiated by physicians with experience in the management of CHC patients.
- Drug plan costs for LDV/SOF should not exceed the drug plan costs of other interferon (IFN)-free regimens for the treatment of CHC. (CDEC, May 2016)
Additional Noteworthy Updates
The CDEC also recommended/stated that:
A Possible Next Step for Hep C Advocates
A possible next step for hep C advocates may be to highlight these changes and to ask governments, who follow the CDEC recommendations, to follow suit.
The Links to the Updated CADTH Canadian Drug Expert Committee Recommendations and Summary Reports on Drugs for Chronic Hepatitis C Infection
About CADTH’s Canadian Drug Expert Committee (CDEC)
CADTH’s CDEC is an advisory board made up of experts and public members (for a lay perspective) that makes recommendations to the publicly funded drug plans about what and what not to cover and how to cover it.
There is excitement over CADTH’s new hepatitis C treatment recommendations report, CADTH Therapeutic Review, Drugs for Chronic Hepatitis C Infection: Recommendations Report, by the Canadian Drug Expert Committee (CDEC).
The report comes after Canadian patient groups, such as PHCN, CTAC, and Action Hepatitis Canada (AHC), were asked to provide feedback to a draft of the recommendations this summer.
Action Hepatitis Canada has written about the new report and is very pleased that patient groups were asked for input, as are we, and that recommendations are in line with some of their feedback. For example, AHC highlighted the first recommendation which reads:
Recommendation 1: CDEC recommends that all patients with CHC infection should be considered for treatment, regardless of fibrosis score. Given the potential impact on health system sustainability of treating all patients with CHC infection on a first-come basis, priority for treatment should be given to patients with more severe disease.
Recommendation 4 stood out for us as the insufficient evidence seemed surprising. It reads:
Recommendation 4: CDEC considered there to be insufficient evidence to make a recommendation for patients with CHC genotype 5 or 6 infection.
Hep C Treatment Recommendations 2, 3, and 5 are as follows:
||Those with genotype 1 (GT1) hepatitis C who have never tried treatment (treatment naive) regardless of liver cirrhosis stage
||Harvoni or Holkira Pak +/- ribavirin for same duration as approved by Health Canada
|Those with GT1 hep C who have tried treatment (treatment experienced) regardless of cirrhosis stage
||Pegylated interferon + ribavirin (PR) for same duration as approved by Health Canada
Sovaldi + ribavirin (12 weeks)
|Those with GT3 hep C without cirrhosis
||Daklinza + Sovaldi (12 weeks)
|Those with GT3 hep C with cirrhosis
||Sovaldi + ribavirin (12 weeks)
|Those with GT4 hep C who are treatment naive and don’t have liver cirrhosis
||Sovaldi + PR (12 weeks)
|Those with GT4 hep C who are treatment experienced or have liver cirrhosis regardless of treatment history
||Insufficient evidence to make a recommendation
||Those with GT1 hep C who have already tried
a protease inhibitor-PR regimen regardless of cirrhosis stage
|Treatment experienced with an all-oral DAA treatment
||Insufficient evidence to make a recommendation
Recommended condition for all patients being treated for hep C: Treatment should be started by hepatologists or physicians experienced with treating chronic hepatitis C. The report also includes recommendations for liver transplant recipients starting on page 22.
Daklinza (generic name daclatasvir), developed by Bristol-Myers Sqibb, just passed its Common Drug Review with the release of the Canadian Drug Expert Committee (CDEC) Final Recommendation.
The Canadian Drug Expert Committee (CDEC) Final Recommendation is important within the Canadian drug approval process as it is sent to the provinces and territories to help them decide on PharmaCare coverage.
The CDEC’s Final Recommendation advocates for Daklinzain combination with Sovaldi (sofosbuvir) to be listed as a treatment for adults with chronic hepatitis C genotype 1, 2, or 3 if the following criteria is met:
Treatment experienced patients without cirrhosis who have not responded to pegylated interferon with ribavirin (PR).
The report highlighted that this does not mean that patients who haven’t been treated, are treatment-naive, should be treated with pegylated interferon with ribavirin (PR) first.
Reasons for the Daklinza Recommendations
The clinical trial ALLY-3 results showed high rates of sustained virologic response (SVR12), cure, for treatment experienced patients with chronic hep C genotype 3.
The manufacturer’s pharmacoeconomic evaluation showed that Daklinza plus Sovaldi was a cost-effective option, when it was compared with 24 weeks of Sovaldi plus ribavirin for patients with hep C genotype 3 who are treatment experienced and don’t have liver cirrhosis. However, Daklinza plus Sovaldi was not a cost-effective option for patients with hep C genotype 3 who are treatment naive and/or have cirrhosis.
Reported Research Gaps
- There aren’t any comparisons between Daklinza and sofosbuvir and the other hep C direct-acting antivirals that are currently used in Canada.
- There is limited data on patients who have cirrhosis, are co-infected with other diseases, such as AIDS, or who have been treated with other hep C direct-acting antivirals but who weren’t cured.
Other Highlighted Information
- Four groups responded to CADTH’s call for input from patient groups. This input successfully explained what it’s like to have hep C, what stigma surrounds hep C, what side effects are like, and the importance of having access to inferferon free/low toxicity treatments with shorter treatment durations and no drug interactions.
Daklinza is approved for use with Sovaldi (sofosbuvir). It may be combined with other drugs for different results in the future.
Daklinza with Sovaldi is a treatment for those with chronic hep C genotype 1, 2, or 3, including those with cirrhosis. It is an all-oral, short-course (12 or 24 weeks), interferon-free, possibly ribavirin-free treatment. A sustained viral response (SVR12), or ”cure”, has been achieved by more than 90% of the patients who have been treated with Daklinza and Sovaldi.