Two hepatitis C medicines delisted from the PBS

• Two direct-acting antiviral (DAA) medicines for chronic hepatitis C infection will be delisted from the PBS
  Daclatasvir was removed from the PBS on 1 October 2020 and sofosbuvir on 1 November 2020.
• Daclatasvir and sofosbuvir were first listed on the PBS in 2016 to improve access to treatment options for hepatitis C infection
  Daclatasvir was prescribed in combination with sofosbuvir as separate tablets, and sofosbuvir was prescribed alone.
• Since these medicines were listed, newer fixed-dose combination (FDC) DAA options for hepatitis C infection have become available
  The newer treatment options have fewer pills and shorter courses and are recommended as first-line treatment.
• The delisting of daclatasvir and sofosbuvir is not expected to have much impact on current prescribing
  Prescriptions for sofosbuvir plus daclatasvir decreased dramatically after the introduction of new DAA regimens.

On 1 October 2020, daclatasvir 30 mg and 60 mg (Daklinza) tablets were delisted from the PBS.¹

Sofosbuvir 400 mg (Sovaldi) tablets were delisted from the PBS on 1 November 2020, however sofosbuvir will remain available on the PBS as a component of other combinations (eg, sofosbuvir 400 mg + ledipasvir 90 mg). The status of sofosbuvir is now ‘Supply Only’. Supply Only items are available on the PBS Schedule for dispensing, but not for prescribing, usually for a period of up to 12 months after they are deleted.²

These delistings are from both the PBS General Schedule (S85) and Highly Specialised Drugs Program (S100).^1,2

See the PBS website for complete details for each item.

On 1 October 2020, the Therapeutic Goods Administration (TGA) acknowledged the removal of daclatasvir 30 and 60 mg tablets from the Australian market, with a notification of medicine supply shortage.³

The sponsor has stated that daclatasvir is being discontinued in countries where it is no longer routinely prescribed or other therapeutic options are available.⁴

Daclatasvir and sofosbuvir were some of the first DAA medicines made available through the PBS when they were listed in March 2016.⁵

Since these medicines were listed, newer treatment options for chronic hepatitis C have become available. They have fewer pills and may have shorter courses of treatment. Additionally, daclatasvir and sofosbuvir are only indicated for treatment of specific genotypes of hepatitis C.^5,6

The newer DAA regimens are pan-genotypic, meaning they are able to be used with all genotypes of the hepatitis C virus. Pan-genotypic regimens are now recommended as first-line treatment for chronic hepatitis C infection.⁶

Both daclatasvir and sofosbuvir as single agents have been removed from Australian treatment guidelines.⁷

Delisting of daclatasvir and sofosbuvir is expected to have little impact on current prescribing. Prescriptions for sofosbuvir plus daclatasvir decreased dramatically after the introduction of the FDC sofosbuvir + velpatasvir (Epclusa), a single-tablet regimen. This FDC, which was PBS-listed in August 2017,⁸ is first-line for treatment-naïve patients.⁶

The TGA has stated that the deletion of daclatasvir from the market is likely to have only a small impact on patients.³

Daclatasvir and sofosbuvir were listed on the PBS as part of the Australian Government’s National Hepatitis C strategy. Changes to the prescribing rules were made in 2016 to allow the broadest possible access to DAA medicines. PBS listing of DAA medicines allows GPs to initiate treatment in primary care, with the goal of substantially increasing the hepatitis C treatment workforce.⁶ From the time of listing up to mid-2017, approximately 19% of people living with hepatitis C started treatment with a DAA medicine. Prior to this, when interferon with ribavirin was used as treatment, annual subsidised treatment uptake did not exceed 2% of the prevalent population per year.⁹

The proportion of people living with hepatitis C who were prescribed DAA treatment by GPs increased from 8% in March 2016 to 39% in June 2017.⁹ GPs were the main prescribers of DAA treatment in all states except NSW and Victoria.⁶ With this trend, we can assume that prescribing of DAAs by GPs would further continue to increase.

From 1 April 2020, authorised nurse practitioners can prescribe hepatitis C treatments under the Highly Specialised Drugs program. Under previous arrangements, they were only able to prescribe under the PBS General Schedule.⁶ This improves availability of hepatitis C treatment for vulnerable populations, such as people living in remote and regional areas, those experiencing homelessness and those in custodial settings.¹⁰

Pan-genotypic regimens are recommended as first-line treatment for chronic hepatitis C. Virtually all patients are suitable for DAA therapy, including those who were previously intolerant of or not eligible for interferon therapy. Several interferon-free regimens combining DAAs are PBS-listed and there are three pan-genotypic FDC DAA regimens listed on the PBS including:⁶

• sofosbuvir 400 mg + velpatasvir 100 mg (Epclusa)
• sofosbuvir 400 mg + velpatasvir 100 mg + voxilaprevir 100 mg (Vosevi)
• glecaprevir 100 mg + pibrentasvir 40 mg (Maviret).

There are still several genotype-specific regimens are listed on the PBS. The hepatitis C genotype should be determined before prescribing these regimens. They are well tolerated and have 95% efficacy in people with or without cirrhosis. They are:⁶

• elbasvir 50 mg + grazoprevir 100 mg (Zepatier), specific for genotypes 1 or 4.¹²
• ledipasvir 90 mg + sofosbuvir 400 mg (Harvoni), specific for genotypes 1, 4, 5 or 6.¹²

The Therapeutic Guidelines have stated that as a result of the significant changes in the management of hepatitis C, the topic is expected to be updated later in 2020.¹³

Changes to the available treatment options may result in some confusion for people living with hepatitis C. They should contact their health professional for review in case any changes to their treatment regimen are required.

Intense monitoring for people receiving treatment with DAAs is usually not required (compared to interferon regimens), due to the high efficacy of these medicines, the lack of a role for response-guided therapy and an improved side effect profile. A review at 12 weeks after completing therapy will be required to document sustained virologic response.⁶

Patients can use the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) website to find a practitioner trained or experienced in hepatitis C.

For more information about management of hepatitis C, see the Australian recommendations for the management of hepatitis C virus infection.