Proposal to fund venetoclax (Venclexta) for chronic lymphocytic leukaemia

Medicines

Consultation Closed

We are seeking feedback on a proposal to fund venetoclax (Venclexta) for the treatment of chronic lymphocytic leukaemia (CLL) from 1 December 2019 through a provisional agreement with AbbVie Limited (AbbVie).

In summary, from 1 December 2019:

  • venetoclax would be funded, in combination with rituximab, for the treatment of CLL that has relapsed within 36 months of previous treatment
  • venetoclax would be funded as monotherapy for the treatment of previously untreated CLL with a specific genetic mutation (17p deletion or TP53 mutation).  

The funding criteria for rituximab would be amended to allow for its use in combination with venetoclax.

Consultation closes at 5 pm on Monday, 16 September 2019 and feedback can be emailed to consult@pharmac.govt.nz.

Who we think will be interested

  • People who have CLL (a type of blood cancer) and their whānau
  • Leukaemia & Blood Cancer New Zealand
  • Haematologists/oncologists
  • Community and hospital pharmacies
  • DHB infusion service providers
  • Other organisations with an interest in cancer treatment

What would the effect be?

Venetoclax in combination with rituximab would be funded for a fixed two-year treatment duration for patients with relapsed/refractory CLL that has relapsed within 36 months of previous treatment. This funding would be irrespective of 17p deletion or TP53 mutation status upon relapse.

Venetoclax monotherapy would also be funded until disease progression for treatment of patients with previously untreated CLL with specific genetic mutations (17p deletion or TP53 mutation).  

Evidence has shown that both venetoclax in combination with rituximab for two years and venetoclax monotherapy until progression are treatment approaches that increase the amount of time a person lives with their disease without it getting worse (called progression free survival or PFS), and are likely to increase overall survival compared with currently funded treatments.

We estimate that approximately 150 patients would be eligible for venetoclax treatment under the proposed criteria in the first year, rising to 230 on treatment by the end of year two and dropping back to approximately 170 on treatment in subsequent years.  

Impact on DHB services

We understand that there would not be an increased demand for genetic testing services as a result of this proposal as patients with CLL currently undergo routine genetic testing for 17p deletion or TP53 mutation prior to treatment to determine eligibility for existing funded treatment options.

Venetoclax is orally administered; however, there would be an impact on DHB infusion services when venetoclax is given in combination with rituximab. Rituximab would be given by intravenous infusion once-monthly for six months duration after completion of the initial dose ramp-up period for venetoclax in relapsed/refractory CLL. We estimate that the impacts to DHB infusion services, if this proposal was progressed, would be:

 

FYE 2019*

FYE 2020

FYE 2021

FYE 2022

FYE 2023

Additional rituximab patients

84*

102

72

72

72

Additional infusions

312*

665

410

410

410

Additional infusion (hours)

624*

1330

820

820

820

*Assumes 7 months of use from proposed implementation date of 1 December 2019
The above estimated impacts assume a two-hour infusion time comprised of a 90-minute infusion plus premedication and observation time(external link). We have not modelled any reduction in the use of currently funded rituximab for CLL.

About chronic lymphocytic leukaemia and venetoclax

CLL is a type of slow-growing blood cancer affecting a type of white blood cell called B-cells. These B-cells cells multiply too quickly, live too long and are unable to function properly. For many people with CLL, the condition can remain stable for many months or even years and may have little if any impact on lifestyle or general health. Over time, an excess number of B-cells crowd the bone marrow and interfere with normal blood cell production which can result in anaemia (causing persistent tiredness), recurrent infections and easy bruising.

Once the disease has progressed to the stage where symptoms become problematic, treatment is usually required. CLL is not usually curable and it typically comes back (relapses) after treatment, meaning that subsequent lines of treatment are often required. Those who have the unfavourable genetic mutations of 17p deletion or TP53 mutation have a considerably worse prognosis and are resistant to usual chemotherapy-based treatments. Our clinical advice indicates that people who have an early relapse or those who have 17p deletion or TP53 gene mutation have a high health need given limited alternative funded treatments.

Venetoclax works by blocking a protein in the body called BCL-2 that helps the abnormal B-cell cells survive. Blocking this protein helps to kill and reduce the number of cancer cells, and may slow the spread of CLL. Our clinical advice is that venetoclax has shown efficacy in the treatment of CLL with 17p deletions or TP53 mutations, which are traditionally resistant to treatment.

Venetoclax is Medsafe approved in combination with rituximab for the treatment of patients with CLL who have received at least one prior therapy. This includes people with 17p deletion or TP53 gene mutations.

Venetoclax is also Medsafe approved as monotherapy for the treatment of relapsed or refractory CLL with 17p deletion or relapsed or refractory CLL for whom there are no other suitable treatment options, but this is not proposed for funding.

Use of venetoclax as monotherapy in patients with previously untreated CLL with 17p deletion or TP53 mutation would be as an unapproved indication.

Venetoclax is given initially as a 5-week schedule of gradual dose increases regardless of whether monotherapy or combination use is intended.

For relapsed/refractory CLL, rituximab would be given by intravenous infusion once-monthly for six months after completion of the initial venetoclax dose ramp-up period. Venetoclax would continue to be given from the first rituximab dose for a total duration of up to two years.

Further information regarding venetoclax dosing and administration in relapsed/refractory CLL can be found in the Medsafe datasheet(external link).

Why we’re proposing this

A funding application for venetoclax in combination with rituximab for the treatment of relapsed or refractory CLL was considered by the Cancer Treatments Subcommittee of PTAC (CaTSoP) in April 2019 [PDF, 710 KB]. CaTSoP recommended that two years’ duration of venetoclax in combination with six cycles of rituximab for the treatment of patients with relapsed/refractory CLL be funded with a high priority subject to certain clinical criteria being met.

A funding application for venetoclax as monotherapy for the treatment of relapsed or refractory CLL with 17p deletion was considered by CaTSoP in September 2018 [PDF, 692 KB]. CaTSoP recommended that venetoclax monotherapy be funded for CLL with 17p deletion or TP53 mutations until disease progression with a high priority subject to certain clinical criteria being met. PHARMAC is not proposing to fund venetoclax monotherapy for relapsed or refractory CLL as we consider the above combination with rituximab (which includes those with 17p deletion or TP53 mutations) would be preferable for this patient group.

CaTSoP in September 2018 also considered that it would be reasonable to fund venetoclax monotherapy until progression for the small number of people (7-10 per year) requiring treatment for previously untreated CLL with 17p deletion or TP53 mutations. This was based on expert opinion, the available data for venetoclax and ibrutinib (another treatment similar to venetoclax), and the few effective funded treatment options in this population. CaTSoP expected a similar benefit in this setting to that expected at relapse.

PTAC has accepted the CaTSoP recommendations relevant to the groups proposed for funding (note that August 2019 PTAC minutes are not yet published).

More information, including links to the PTAC and Subcommittee minutes, can be found in the Application Tracker records for venetoclax(external link).

Details about our proposal

Venetoclax would be listed in Section B and in Part II of Section H of the Pharmaceutical Schedule from 1 December 2019 at the following prices (ex-manufacturer, excluding GST):

Chemical

Formulation

Brand

Pack size

Proposed price and subsidy

Venetoclax

Tab 10 mg

Venclexta

14

$95.78

Venetoclax

Tab 50 mg

Venclexta

7

$239.44

Venetoclax

Tab 100 mg

Venclexta

120

$8,209.41

Venetoclax

Tab 14 x 10 mg, 7 x 50 mg, 21 x 100 mg

Venclexta

42

$1,771.86

A confidential rebate would apply to Venclexta that would reduce the net price to the Funder.

Venetoclax would be listed in Section B of the Pharmaceutical Schedule subject to the following Special Authority criteria (initial approval valid for 7 months to account for dose ramp-up):

Special Authority for Subsidy – Retail Pharmacy – Specialist

Initial application (relapsed/refractory chronic lymphocytic leukaemia) - only from a relevant specialist or medical practitioner on the recommendation of a relevant specialist. Approvals valid for 7 months for applications meeting the following criteria:

All of the following:

  1. Patient has chronic lymphocytic leukaemia requiring treatment; and
  2. Patient has received at least one prior therapy for chronic lymphocytic leukaemia; and
  3. Patient has not previously received venetoclax; and
  4. The patient’s disease has relapsed within 36 months of previous treatment; and
  5. Venetoclax to be used in combination with six 28-day cycles of rituximab commencing after the 5-week dose titration schedule with venetoclax; and
  6. Patient has an ECOG performance status of 0-2.

Renewal application (relapsed/refractory chronic lymphocytic leukaemia) - only from a relevant specialist or medical practitioner on the recommendation of a relevant specialist. Approvals valid for 6 months for applications meeting the following criteria:

Both:

  1. Treatment remains clinically appropriate and the patient is benefitting from and tolerating treatment; and
  2. Venetoclax is to be discontinued after a maximum of 24 months of treatment following the titration schedule unless earlier discontinuation is required due to disease progression or unacceptable toxicity. 

Initial application (previously untreated chronic lymphocytic leukaemia with 17p deletion or TP53 mutation*) - only from a relevant specialist or medical practitioner on the recommendation of a relevant specialist. Approvals valid for 6 months for applications meeting the following criteria:

All of the following:

  1. Patient has previously untreated chronic lymphocytic leukaemia; and 
  2. There is documentation confirming that patient has 17p deletion by FISH testing or TP53 mutation by sequencing; and
  3. Patient has an ECOG performance status of 0-2.


Renewal application (previously untreated chronic lymphocytic leukaemia with 17p deletion or TP53 mutation*) - only from a relevant specialist or medical practitioner on the recommendation of a relevant specialist. Approvals valid for 6 months for applications meeting the following criteria:

  1. Treatment remains clinically appropriate and the patient is benefitting from and tolerating treatment.

Note: ‘Chronic lymphocytic leukaemia (CLL)’ includes small lymphocytic lymphoma (SLL). Indication marked with * is an unapproved indication.

The same restrictions would apply in Part II of Section H of the Pharmaceutical Schedule (the Hospital Medicines List; HML).

Venclexta would have protection from delisting and subsidy reduction until 30 November 2022.

The following changes would be made to the rituximab Special Authority criteria for CLL in Section B of the Pharmaceutical Schedule to allow concurrent use (changes in bold and strikethrough). Note that all other criteria that currently apply to rituximab would remain unchanged.

Special Authority for Subsidy

Initial application — (Chronic lymphocytic leukaemia) from any relevant practitioner. Approvals valid for 12 months for applications meeting the following criteria:

All of the following:

Renewal — (Chronic lymphocytic leukaemia) from any relevant practitioner. Approvals valid for 12 months for applications meeting the following criteria:

Both:

Note: 'Chronic lymphocytic leukaemia (CLL)' includes small lymphocytic lymphoma. A line of chemotherapy treatment is considered to comprise a known standard therapeutic chemotherapy regimen and supportive treatments. 'Good performance status' means ECOG score of 0-1, however, in patients temporarily debilitated by their CLL disease symptoms a higher ECOG (2 or 3) is acceptable where treatment with rituximab is expected to improve symptoms and improve ECOG score to < 2.

To provide feedback

Send us an email: consult@pharmac.govt.nz by 5 pm on Monday, 16 September 2019.

All feedback received before the closing date will be considered by PHARMAC’s Board (or its delegate) prior to making a decision on this proposal.

We particularly seek your feedback on the following areas:

  1. Do you consider it reasonable to fund venetoclax monotherapy for the treatment of previously untreated CLL with 17p deletion or TP53 mutations?
  2. Do you consider that the proposed Special Authority criteria for venetoclax and rituximab are appropriate?

Feedback we receive is subject to the Official Information Act 1982 (OIA) and we will consider any request to have information withheld in accordance with our obligations under the OIA. Anyone providing feedback, whether on their own account or on behalf of an organisation, and whether in a personal or professional capacity, should be aware that the content of their feedback and their identity may need to be disclosed in response to an OIA request.

We are not able to treat any part of your feedback as confidential unless you specifically request that we do, and then only to the extent permissible under the OIA and other relevant laws and requirements. If you would like us to withhold any commercially sensitive, confidential proprietary, or personal information included in your submission, please clearly state this in your submission and identify the relevant sections of your submission that you would like it withheld. PHARMAC will give due consideration to any such request.