Proposal to widen access to rituximab and change the funded brand for all funded indications excluding rheumatoid arthritis

Medicines

Consultation Closed

PHARMAC is seeking your feedback on a proposal to make changes to the funded brand of rituximab, a biologic medicine used to treat a range of cancer, blood and autoimmune conditions, from 1 March 2020.

What we’re proposing

If the proposal is approved, the following changes would occur:  

  • from 1 March 2020, a biosimilar rituximab (Riximyo, supplied by Novartis) would be listed and would be the only funded brand of rituximab for all funded indications excluding rheumatoid arthritis from 1 September 2020 until 30 June 2023.
  • the current funded brand of rituximab (Mabthera, supplied by Roche) would remain fully funded for patients with rheumatoid arthritis only.
  • from 1 March 2020, funded access to rituximab (Riximyo brand only) would be widened to include the following new uses:
    • maintenance for CD20+ low grade or follicular B-cell non-Hodgkin’s lymphoma
    • graft versus host disease
    • antisynthetase syndrome with lung disease
    • some severe neurological conditions
    • amending existing criteria for transplant indications to allow use for any organ.

This proposal results from a competitive process for the supply of funded rituximab. It would release significant funds for PHARMAC to invest in other medicines for the benefit of New Zealanders.

Feedback to this consultation will help us decide if this proposal should be approved. Consultation closes at 12pm on Thursday, 14 November 2019 and feedback can be emailed to procurement@pharmac.govt.nz.

Who we think will be interested

  • People currently using rituximab and their family, whānau or caregivers
  • Consumer support groups for people living with conditions that are treated with rituximab
  • Clinicians who treat people with cancer, blood and autoimmune conditions (haematologists, rheumatologists, neurologists, transplant specialists, general practitioners, nurse specialists)
  • Hospital and community pharmacists, DHBs and wholesalers
  • Suppliers of rituximab and biologic medicines

What would the effect be?

From 1 March 2020, two brands of rituximab would be funded for use in different clinical indications. Each product would have separate Special Authority funding criteria. Prescribers and hospital pharmacists would need to work together to manage the transition in their hospital. PHARMAC would provide information and resources about biosimilar rituximab to support the change.  

Proposed funding of rituximab

Rituximab brand

From 1 March 2020

From 1 September 2020

Mabthera

For all currently funded indications but not new funded indications(external link)

For rheumatoid arthritis only

Riximyo (biosimilar)

For all currently funded indications except for rheumatoid arthritis

For new funded indications

For current and new funded indications, except for rheumatoid arthritis

Current patients

Most patients currently on treatment with rituximab would not be impacted by this proposal. Patients could continue to receive their current brand of rituximab until their treatment course is complete, if this is before 1 September 2020.

Current patients who would require treatment after 1 September 2020, for any indication except rheumatoid arthritis, would need to transition to biosimilar rituximab (Riximyo). We expect that this would only be a small number of current patients.

This change would be carefully supported by the treating clinician, working with the patient and family/caregivers. PHARMAC would communicate with relevant clinicians, pharmacies, support services and DHB services regarding the change process.

Patients with rheumatoid arthritis would continue to receive the Mabthera brand of rituximab. Legal patents on the use of Mabthera for the treatment of rheumatoid arthritis prevent the use of other brands for this condition at this time.

If a patient does not tolerate the new brand of rituximab for a clinical reason, and it is safe to consider further treatment with rituximab, PHARMAC would consider a Named Patient Pharmaceutical Assessment (NPPA application from a clinician to use the Mabthera brand of rituximab for an individual patient.

New patients

From 1 March 2020 patients starting treatment with rituximab for existing funded indications excluding rheumatoid arthritis could receive either the Riximyo or Mabthera brand.

Patients starting treatment with rituximab for rheumatoid arthritis would receive the Mabthera brand.

Patients starting treatment with rituximab for any of the proposed new indications would receive the Riximyo brand.

If DHBs started new patients on Riximyo from 1 March 2020 (for all funded indications except for rheumatoid arthritis), we would expect that only a small number of new patients would need to transition during their treatment course. As noted above, the change would be carefully supported.

For prescribers and hospital pharmacies

From 1 March 2020:

  • Either the Mabthera brand or the Riximyo brand could be prescribed for existing and new patients for all existing funded indications except rheumatoid arthritis
  • Only the Mabthera brand could be prescribed for rheumatoid arthritis
  • Only the Riximyo brand could be prescribed for the new indications

From 1 September 2020:

  • Only the Riximyo brand could be prescribed for all funded indications (current and new), excluding rheumatoid arthritis
  • Only the Mabthera brand could be prescribed for rheumatoid arthritis

To claim a subsidy, the correct brand would need to be used for the correct indication. PHARMAC would take steps to ensure that indication specificity/exclusivity also applied to rituximab procured via Contract Manufacturers.

As noted above, if DHBs started new patients on Riximyo from 1 March 2020 (for all funded indications except for rheumatoid arthritis), we would expect that only a small number of patients would need to transition during their treatment course.

More information would be available during the transition period for prescribers and pharmacists on PHARMAC’s website.

Impact on DHB services

From 1 March 2020, the confidential net price would reduce for rituximab for all funded indications excluding rheumatoid arthritis.

There would be some impact on DHB infusion services if access to rituximab is widened to include maintenance treatment for patients with non-Hodgkin’s lymphoma. Rituximab would be given by intravenous infusion once every two months for two years after completion of induction with first-line systemic chemotherapy.

We estimate that the impacts to DHB infusion services, if this proposal was progressed, would be:

  FYE 2020 * FYE 2021 FYE 2022 FYE 2023 FYE 2024
Additional rituximab patients on treatment (2 years duration) 32 131 209 229 252
Additional infusions  64  788  1,252  1,376  1,512
Additional infusion (hours) 128 1,576 2,504 2,752 3,024
4 months

The above estimated impacts assume a two-hour infusion time comprised of a 90-minute infusion plus premedication and observation time(external link). For the purposes of above, we have not modelled any reduction in the use of currently funded rituximab for Non-Hodgkin’s Lymphoma due to delayed progression, or early cessation of maintenance treatment.

About rituximab and its uses

Rituximab is a monoclonal antibody (a biologic medicine), that destroys B cells by acting against CD20 proteins on their surface. Rituximab is funded for a range of cancer, blood and autoimmune conditions, which include both approved and unapproved indications.

Rituximab is usually dosed infrequently, often in cycles and is not given again for some months. For some indications it is only used for a fixed amount of time. This includes patients with blood cancers who receive treatment for up to 6 months, and patients with autoimmune conditions who receive one course of treatment (of between 1 to 4 doses) and then may receive further treatment in 6 to 12 months only if needed. 

Rituximab is given by an extended intravenous infusion (approximately 1.5 to 3 hours, longer for first infusion) usually in a DHB Hospital outpatient clinic setting. Dosing and the number of infusions varies depending on the indication. 

Current funding

Rituximab (Mabthera, supplied by Roche) is funded for a range of indications(external link). Mabthera has several NZ patents relating to its use for treatment of rheumatoid arthritis that expire in 2024 and 2026. This prevents the use of any other brand of rituximab for rheumatoid arthritis at this time.

Rituximab has been listed on the Pharmaceutical Schedule since 2005, subject to Special Authority funding restrictions. From 1 April 2019, DHBs are now required to submit subsidy claims for all rituximab patients. This previously only applied to rituximab for use in blood cancers.

Dispensing data indicate that approximately 1000 patients received rituximab for a cancer indication in 2018. We estimate that approximately 850 patients receive rituximab for non-cancer indications.

There is also a number of individual patients that use rituximab for various indications through the Named Patient Pharmaceutical Assessment (NPPA) funding pathway. In 2018, there were 52 initial applications (30 approvals) through NPPA for rituximab.

Proposed biosimilar rituximab

Riximyo is Medsafe approved for the same indications as the reference rituximab (Mabthera). This includes:

  • CD20 positive, previously untreated low-grade or follicular, B-cell non-Hodgkin’s lymphoma in combination with chemotherapy
  • CD20 positive, relapsed or chemoresistant low grade or follicular, B-cell non-Hodgkin's lymphoma
  • CD20 positive, diffuse large B-cell non-Hodgkin’s lymphoma in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy
  • maintenance treatment of patients with CD20 positive, low grade or follicular, B-cell non-Hodgkin’s lymphoma
  • chronic lymphocytic leukaemia (CLL)
  • rheumatoid arthritis
  • granulomatosis with polyangiitis and microscopic polyangiitis

The comparability of Riximyo with Mabthera has been demonstrated with regard to physicochemical characteristics and pharmacology, efficacy and safety outcomes. The evidence for comparability supports the use of Riximyo for the approved indications (see Australian datasheet(external link)).

Riximyo has been used in in many European countries since 2017 and is used in the United Kingdom and Australia. Real-world evidence supports the use of biosimilar rituximab. See below for summary of clinical advice for biosimilar rituximab. 

Compounding

DHBs are able to procure rituximab prepared for infusion from a third-party compounder (a Contract Manufacturer) provided that the DHB ensures that the all of the component pharmaceuticals used in its manufacture are listed on the Pharmaceutical Schedule and comply with any national contracting obligations. The “Inj 1 mg for ECP” formulation of rituximab listed in Section B of the Schedule allows DHBs to claim a subsidy for the correct number of mg provided by the compounder.

We are aware of extended stability data that supports a prolonged shelf life of rituximab infusions prepared with Mabthera. There is published data to support similar extended stability with Riximyo (Lamanna et al. J Oncol Pharm Practice 2017;25(2):269-78(external link)).

Why we’re proposing this

PHARMAC released a Request for Proposal (RFP) for the supply of rituximab in the community and DHB hospitals on 16 July 2019.

Several biosimilar rituximab products are now approved by Medsafe for use in New Zealand. A biosimilar is a highly similar, comparable version of an approved biologic medicine. The availability of biosimilars provided PHARMAC with the opportunity to promote competition and reduce the cost of rituximab.

As a result of the RFP, PHARMAC has entered into a provisional agreement with Novartis New Zealand Limited for the sole supply of rituximab (Riximyo) for all funded indications excluding rheumatoid arthritis.

This proposal would release significant funds for PHARMAC to invest in other medicines for the benefit of New Zealanders. It would also allow widening access to rituximab for other uses. Feedback from this consultation will help us decide if this agreement should be confirmed.

We understand there is interest in funding for other uses of rituximab. If this proposal is approved, PHARMAC intends to seek further clinical advice from the relevant Subcommittees to determine if there are other changes to rituximab criteria that could be considered at a later date. We welcome funding applications for rituximab for treatment in other areas of unmet health need.

PHARMAC remains supportive of, and will continue to consider, funding other biosimilar medicines in the future. We remain committed to implementing changes to introduce biosimilar medicines where they would release additional funds for PHARMAC to invest in other medicines for the benefit of New Zealanders.

Clinical advice

In February 2019, the Pharmacology and Therapeutics Advisory Committee (PTAC) reviewed a funding application for a biosimilar rituximab and recommended that PHARMAC run a competitive process for the supply of rituximab for currently funded indications. Overall, PTAC considered that biosimilar rituximab (CT-P10 brand, Truxima or Ritemvia, supplied by Celltrion) would provide the same or similar quality, safety and efficacy to rituximab (Mabthera) and that patients could be changed to biosimilar rituximab with implementation support. PTAC advised that it would be possible to consider a dual listing of a biosimilar rituximab alongside the reference product for separate indications with appropriate implementation support. The full record of the meeting is available on our website [PDF, 796 KB].

In October 2019, the Cancer Treatments Subcommittee of PTAC (CaTSoP), reviewed clinical data for Riximyo (biosimilar rituximab supplied by Novartis). CaTSoP advised that it would be clinically acceptable for Riximyo to be listed and be the only available rituximab product for all funded indications, if the cost saving is worthwhile and supply is secured. The Subcommittee recommended that PHARMAC should consider widening access to rituximab as part of the biosimilar transition, which should include a review of commonly approved rituximab NPPA applications. The Subcommittee considered the comparability of Riximyo and Mabthera has been sufficiently demonstrated with regard to physicochemical characteristics, pharmacology, efficacy and safety outcomes. The clinical evidence for comparability is of good quality and supports the use of Riximyo for all funded indications.

The record of this meeting is not yet available and will be published on our website in the future once finalised. 

Widening access

We propose to widen funded access to rituximab for a range of uses. This includes an application previously considered for Pharmaceutical Schedule listing and several other uses we have considered and approved for a small number of a patients considered through our exceptions process (NPPA). 

A funding application for the widening of access to rituximab for maintenance treatment in CD20+ low grade or follicular B-cell non-Hodgkin's lymphoma following initial treatment induction was reviewed by CaTSoP in April 2018. The Subcommittee recommended that rituximab be listed for this indication with a medium priority. A proposal for this indication has been ranked against other funding options.

More information, including links to the PTAC and Subcommittee minutes, can be found in the Application Tracker records for rituximab for CD20+ low grade or follicular B-cell non-Hodgkin’s lymphoma.

The following table provides an estimate of patient numbers and required dosing for the proposed new or amended criteria: 

New or amended criteria

Patient numbers

Maintenance treatment in CD20+ low grade or follicular B-cell Non-Hodgkin's Lymphoma

Approximately 100 additional new patients per year on 2 years maintenance

Transplant indications

  • ABO incompatible*
  • Antibody mediated transplant rejection*
  • Graft versus host disease*

Less than 5 patients per year for each

Severe antisynthetase syndrome*

Less than 5 patients per year

Anti NMDA receptor encephalitis*

Less than 20 patients per year

Severe chronic inflammatory demylelinating neuropathy*

Less than 5 patients per year

*unapproved indication

 

Details about our proposal

From 1 March 2020, Riximyo would be listed in Section B and Part II of Section H of the Pharmaceutical Schedule as follows:

Chemical Formulation Brand Pack size
Rituximab (Riximyo) Inj 100 mg per 10 ml vial Riximyo 2
Rituximab (Riximyo) Inj 500 mg per 50 ml vial Riximyo 1
Rituximab (Riximyo) Inj 1 mg for ECP Baxter 1 mg

Rituximab (Riximyo) would be listed as a PCT only-Specialist pharmaceutical in Section B of the Pharmaceutical Schedule.

The price and subsidy would be notified should PHARMAC decide to progress the proposal following consideration of consultation feedback. A confidential rebate would apply to all presentations of Riximyo, which would reduce the net price to the funder.

From 1 March 2020, new Special Authority criteria would apply to biosimilar rituximab (Riximyo), based on current rituximab criteria with amendments and additions. The proposed changes are to remove the criteria for rheumatoid arthritis and to include the following new or amended uses (additions in bold and deletions in strikethrough – relevant criteria only shown):Amended criteria

Maintenance treatment in CD20+ low grade or follicular B-cell Non-Hodgkin's Lymphoma

Initial application - indolent, low-grade lymphomas or hairy cell leukaemia*

Applications from any relevant practitioner. Approvals valid for 9 months.

Either:

1.  Both:

1.1   The patient has indolent low grade NHL or hairy cell leukaemia* with relapsed disease following prior chemotherapy; and
1.2   To be used for a maximum of 6 treatment cycles; or

2.  Both :

2.1   The patient has indolent, low grade lymphoma or hairy cell leukaemia* requiring first-line systemic chemotherapy; and
2.2   To be used for a maximum of 6 treatment cycles

Note: 'Indolent, low-grade lymphomas' includes follicular, mantle, marginal zone and lymphoplasmacytic/Waldenstrom macroglobulinaemia. *Unapproved indication. 'Hairy cell leukaemia' also includes hairy cell leukaemia variant.

Renewal - indolent, low-grade lymphomas or hairy cell leukaemia*

Applications from any relevant practitioner. Approvals valid for 912 months.

Either:

1.  All of the following:

1.1   The patient has indolent, low-grade NHL or hairy cell leukaemia* with relapsed disease following prior chemotherapy; and
1.2   The patient has had a rituximab treatment-free interval of 12 months or more; and\
1.3   To be used for no more than 6 treatment cycles; or

2.  Both:

2.1   Rituximab is to be used for maintenance in CD20+ low grade or follicular B-cell NHL following induction with first-line systemic chemotherapy, and
2.2   Patient is intended to receive rituximab maintenance therapy for 2 years at a dose of 375 mg/m2 every 8 weeks (maximum of 12 cycles).

Note: 'Indolent, low-grade lymphomas' includes follicular, mantle, marginal zone and lymphoplasmacytic/Waldenstrom macroglobulinaemia. *Unapproved indication. 'Hairy cell leukaemia' also includes hairy cell leukaemia variant.

ABO incompatible organ transplant

Initial application – (ABO-incompatible renal organ transplant) from any relevant practitioner only from a nephrologist or Practitioner on the recommendation of a nephrologist. Approvals valid without further renewal unless notified where patient is to undergo an ABO-incompatible renal solid organ transplant*. Note: Indications marked with * are unapproved indications

Antibody mediated organ transplant rejection

Initial application – (Antibody-mediated renal organ transplant rejection) from any relevant practitioner. only from a nephrologist or Practitioner on the recommendation of a nephrologist. Approvals valid without further renewal unless notified where patient has been diagnosed with antibody-mediated renal organ transplant rejection*. Note: Indications marked with * are unapproved indications.

New criteria

Severe antisynthetase syndrome

Initial application – (severe antisynthetase syndrome) from any relevant practitioner. Approvals valid for 12 months for applications meeting the following criteria:

All of the following:

1. Patient has confirmed antisynthetase syndrome; and

2. Patient has severe, immediately life or organ threatening disease, including interstitial lung disease; and

3. Either

3.1   Treatment with at least 3 immunosuppressants (oral steroids, cyclophosphamide, methotrexate, mycophenolate, ciclosporin, azathioprine) has not be effective at controlling active disease; or
3.2   Rapid treatment is required due to life threatening complications; and

4. Maximum of four 1000mg infusions of rituximab.

Renewal – (severe antisynthetase syndrome) from any relevant practitioner. Approvals valid for 12 months for applications meeting the following criteria:

All of the following:

  1. Patient’s disease has responded to the previous rituximab treatment with demonstrated improvement in inflammatory markers, muscle strength and pulmonary function; and
  2. The patient has not received rituximab in the previous 6 months; and
  3. Maximum of two cycles of 2 x 1000mg infusions of rituximab given two weeks apart.

    Graft versus host disease

    Initial application – (graft versus host disease) from any relevant practitioner. Approvals valid without further renewal unless notified for applications meeting the following criteria.

    All of the following:

    1. Patient has refractory graft versus host disease following transplant; and
    2. Treatment with at least 3 immunosuppressants (oral steroids, ciclosporin, tacrolimus, mycophenolate, sirolimus) has not be effective at controlling active disease; and
    3. The total rituximab dose used would not exceed the equivalent of 375 mg/m² of body surface area per week for a total of 4 weeks.

    Severe chronic inflammatory demylelinating neuropathy

    Initial application – (severe chronic inflammatory demyelinating polyneuropathy) only from a neurologist or any other medical practitioner on the recommendation of a neurologist. Approvals valid for 6 months for applications meeting the following criteria.

    All of the following

    1. Patient has severe chronic inflammatory demyelinating polyneuropathy (CIPD); and

    2. Either

    2.1   Treatment with at least 3 immunosuppressants (oral and intravenous steroids, cyclophosphamide, ciclosporin, tacrolimus, mycophenolate) has not been effective at controlling active disease; or
    2.2   Rapid treatment is required due to life threatening complications; and

    3. One of the following dose regimens is to be used: 375 mg/m2 of body surface area per week for a total of four weeks, or 500 mg once weekly for four weeks, or two 1,000 mg doses given two weeks apart.

    Renewal – (severe chronic inflammatory demyelinating polyneuropathy) only from a neurologist or any other medical practitioner on the recommendation of a neurologist. Approvals valid for 6 months for applications meeting the following criteria.

    All of the following:

    1. Patient’s disease has responded to the previous rituximab treatment with demonstrated improvement in neurological function compared to baseline; and
    2. The patient has not received rituximab in the previous 6 months; and
    3. One of the following dose regimens is to be used: 375 mg/m2 of body surface area per week for a total of four weeks, or 500 mg once weekly for four weeks, or two 1,000 mg doses given two weeks apart.

    Anti-NMDA receptor autoimmune encephalitis

    Initial application – (anti-NMDA receptor autoimmune encephalitis) only from a neurologist or any other medical practitioner on the recommendation of a neurologist. Approvals valid for 6 months for applications meeting the following criteria.

    All of the following

    1. Patient has severe anti-NMDA receptor autoimmune encephalitis; and

    2. Either

    2.1   Treatment with at least 3 immunosuppressants (oral and intravenous steroids, cyclophosphamide, ciclosporin, tacrolimus, mycophenolate) has not been effective at controlling active disease; or
    2.2   Rapid treatment is required due to life threatening complications; and

    3. One of the following dose regimens is to be used: 375 mg/m2 of body surface area per week for a total of four weeks, or 500 mg once weekly for four weeks, or two 1,000 mg doses given two weeks apart.

    Renewal – (anti-NMDA receptor autoimmune encephalitis) only from a neurologist or any other medical practitioner on the recommendation of a neurologist. Approvals valid for 6 months for applications meeting the following criteria.

    All of the following:

    1. Patient’s disease has responded to the previous rituximab treatment with demonstrated improvement in neurological function; and
    2. The patient has not received rituximab in the previous 6 months; and
    3. The patient has experienced a relapse and now requires further treatment; and
    4. One of the following dose regimens is to be used: 375 mg/m2 of body surface area per week for a total of four weeks, or 500 mg once weekly for four weeks, or two 1,000 mg doses given two weeks apart.

    The same restrictions for the Riximyo brand of rituximab would apply in Part II of Section H of the Pharmaceutical Schedule (the Hospitals Medicine List; HML).

    From 1 September 2020, Riximyo would be awarded Sole Subsidised Supply status in the Pharmaceutical Schedule (the only available brand of rituximab in DHB hospitals) for all funded indications except for rheumatoid arthritis until 30 June 2023.

    Changes to the listing of Mabthera

    From 1 March 2020, the Pharmaceutical Schedule listing for the Mabthera brand of rituximab would be amended to specify the brand at the chemical level as follows (additions in bold):

    Chemical

    Formulation

    Brand

    Pack size

    Rituximab (Mabthera)

    Inj 100 mg per 10 ml vial

    Mabthera

    2

    Rituximab (Mabthera)

    Inj 500 mg per 50 ml vial

    Mabthera

    1

    Rituximab (Mabthera)

    Inj 1 mg for ECP

    Baxter

    1 mg

    From 1 March 2020, the current Special Authority criteria for Mabthera would continue to apply. Mabthera would not be able to be used for the new/amended indications outlined above for the Riximyo brand.

    From 1 September 2020, the Special Authority criteria for Mabthera would be amended to only include the currently funded rheumatoid arthritis uses. 

    To provide feedback

    Send us an email: procurement@pharmac.govt.nz by 12pm on Thursday 14 November 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.

    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.