Decision to widen access to rituximab and award sole supply

Medicines

Decision

PHARMAC has made a decision to make changes to the funding of rituximab, including widening access and changing brands.

From 1 March 2020

  • A biosimilar rituximab (Riximyo, supplied by Novartis) will be funded.
  • The Riximyo brand will be funded for:
    • all new and existing patients requiring rituximab except patients with rheumatoid arthritis
    • new indications:
      • maintenance for CD20+ low grade or follicular B-cell non-Hodgkin’s lymphoma
      • graft versus host disease
      • antisynthetase syndrome with lung disease
      • anti NMDA receptor encephalitis
      • severe chronic inflammatory demyelinating neuropathy
      • amending existing criteria for transplant indications to allow use for any organ.
  • The currently funded brand of rituximab (Mabthera, supplied by Roche) will be funded for:
    • existing patients for all indications except the new indications shown above
    • new and existing patients with rheumatoid arthritis.

From December 2020

  • The Riximyo brand will be funded for all indications, including the new indications listed above, except for rheumatoid arthritis, and will be the only funded brand of rituximab for these indications until 30 September 2023.
  • The Mabthera brand will be funded for patients with rheumatoid arthritis only.

Any changes to the original proposal

This decision was subject to a consultation letter dated 31 October 2019

Following consultation, the following changes were made to the original proposal:

  • the transition period has been extended from six months to nine months, commencing on 1 March 2020 and ending on 1 December 2020.
  • the sole supply period will start on 1 December 2020 and has been extended to end on 30 September 2023.
  • new patients will need to start on Riximyo for all funded indications except for rheumatoid arthritis from 1 March 2020.
  • the funding criteria for the new neurological indications for anti-NMDA receptor encephalitis and severe chronic inflammatory demyelinating neuropathy have been amended to include a trial of immunoglobulin and plasma exchange prior to rituximab.

Who we think will be most 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

Details about the decision

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

Summary of funding of rituximab

Rituximab brand

From 1 March 2020

From 1 December 2020

Riximyo (biosimilar)

For new and existing patients for all currently funded indications except for rheumatoid arthritis

For new funded indications

For all current and new funded indications, except for rheumatoid arthritis

Mabthera

For new and existing patients with rheumatoid arthritis

For renewals (but not for initials) for existing patients for all currently funded indications but not for new funded indications

For rheumatoid arthritis only

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

Patients who have started on Mabthera and require treatment after 1 December 2020, for any indication except rheumatoid arthritis, will need to transition to biosimilar rituximab (Riximyo). Given the 9-month transition period we expect that this would only be a very small number of current patients. This change will be carefully supported by the treating clinician, working with the patient and family/caregivers. PHARMAC will communicate with relevant clinicians, pharmacies, support services and DHB services regarding the change process.

Patients with rheumatoid arthritis will 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 is unable to use the new brand of rituximab for a clinical reason, and it is safe to consider further treatment with rituximab, PHARMAC will consider a Named Patient Pharmaceutical Assessment (NPPA) application from a clinician to use the Mabthera brand of rituximab for an individual patient.

New listing for Riximyo

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

Chemical

Formulation

Brand

Pack size

Price & Subsidy

Rituximab (Riximyo)

Inj 100 mg per 10 ml vial

Riximyo

2

$275.33

Rituximab (Riximyo)

Inj 500 mg per 50 ml vial

Riximyo

1

$688.20

Rituximab (Riximyo)

Inj 1 mg for ECP

Baxter

1 mg

$1.38

Rituximab (Riximyo) will be listed as a PCT only-Specialist pharmaceutical in Section B of the Pharmaceutical Schedule. A confidential rebate applies to all presentations of Riximyo, which reduces the net price to the funder. 

Changes to listing for Mabthera

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

Chemical

Formulation

Brand

Pack size

Price & Subsidy

Rituximab
(Mabthera)

Inj 100 mg per 10 ml vial

Mabthera

2

$1,075.50

Rituximab
(Mabthera)

Inj 500 mg per 50 ml vial

Mabthera

1

$2,688.30

Rituximab
(Mabthera)

Inj 1 mg for ECP

Baxter

1 mg

$5.64

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

Special Authority and hospital restriction changes

Changes for Riximyo

The Special Authority criteria and hospital indication restrictions will be amended from 1 March 2020 to widen access to 7 new or amended indications for the Riximyo brand.

For full details of the changes to the Special Authority criteria please refer to the consultation letter

Following consultation, we have made some changes to the original proposed criteria for anti-NMDA receptor encephalitis and severe chronic inflammatory demyelinating neuropathy. Changes are outlined below (changes to the original proposal in bold and strikethrough):

Special Authority for Subsidy

Initial application – (severe chronic inflammatory demyelinating polyneuropathy) only from a neurologist or 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
Both

2.1.1   Treatment with steroids and intravenous immunoglobulin and/or plasma exchange has not been effective at controlling active disease; and
2.1.2   At least one other immunosuppressant (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 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.

Initial application – (anti-NMDA receptor autoimmune encephalitis) only from a neurologist or 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;
Both

2.1.1   Treatment with steroids and intravenous immunoglobulin and/or plasma exchange has not been effective at controlling active disease; and
2.1.2   At least one other immunosuppressant (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 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 will apply in Part II of Section H of the Pharmaceutical Schedule (the Hospitals Medicine List; HML).

Changes for Mabthera

From 1 March 2020, the current Special Authority criteria for Mabthera will change. Mabthera will only be funded for patients already on treatment (no new patients) for all funded indications excluding rheumatoid arthritis. Initial applications will be removed from the Special Authority application form. Mabthera will not be funded for the new/amended indications outlined above for the Riximyo brand.

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

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

Support for the changes

PHARMAC staff will work with health care professionals and consumer organisations to provide information on biosimilar rituximab.  This is likely to include education sessions for clinical DHB staff and patient information on rituximab.  PHARMAC staff will work with DHB staff in the development of these resources.

Information will also be available during the transition period for prescribers and pharmacists on PHARMAC’s website.

Our response to what you told us

We’re really grateful for the time people took to respond to this consultation. Responses were generally supportive of the proposal and of widening access to rituximab. A summary of the main themes raised in feedback and our responses to the feedback received is provided below. All consultation responses received have helped inform our decisions and will continue to guide us as we implement this brand change across the country.

Theme

PHARMAC Comment

Concerns that the proposal changes the dose that is available for Neuromyelitis Optica Spectrum Disorder (NMOSD). 

 

There is no change to the dosing of rituximab that is currently available for people with NMOSD. The same vial strengths will be available for both Riximyo and Mabthera and dosing can be adjusted as appropriate for the patient.

Request to consider including dermatology indications including severe bullous disorders, particularly pemphigus.

 

We would welcome a funding application for these indications. PHARMAC has considered several NPPA indications for severe skin disorders; however, we consider that additional clinical advice would be required to develop appropriate funding criteria.

Request to consider changes to the restrictions for the new neurological indications, because there is limited evidence for standard immunosuppressants for these conditions and use of intravenous immunoglobulin and/or plasma exchange (PLEX) would be more suitable alternatives so should be included in the criteria.

The Special Authority criteria for anti-NMDA receptor encephalitis and severe chronic inflammatory demyelinating neuropathy have been amended to include these changes. Immunoglobulin and plasma exchange are included in the list of other treatments to try prior to rituximab.

Query about extrapolation to other indications where there is not data with Riximyo.

Riximyo is approved by Medsafe for the same indications as Mabthera. Extrapolation of indications is considered by Medsafe. We are aware that this is important and we will ensure that there are appropriate resources to reassure patients and advocacy groups of the regulatory framework for biosimilars and the processes involved in extrapolating indications from the data available.

Stability information provided in the consultation indicates stability of Riximyo once diluted. There would be no impact on ability to compound and prepare Riximyo.

PHARMAC is aware this is an important consideration with considering intravenous biologic agents. There is published data to support extended stability with Riximyo.

Request for consideration of pharmacovigilance requirements following the listing of Riximyo.

Medsafe is responsible for pharmacovigilance and post-marketing surveillance of medicines in New Zealand. PHARMAC will work with Medsafe to develop educational materials regarding biosimilars that will help inform healthcare professionals and patient advocacy groups about pharmacovigilance monitoring and reporting of biosimilars in New Zealand.  

Request for patient focussed information available regarding biosimilars.

PHARMAC plans to develop resources that will help support healthcare professionals and advocacy groups to provide information to patients. We will also develop some specific information for patients.

Concerns that new infusion treatments have additional costs and resource impacts for DHBs.

 

We acknowledge that widening access to an infusion treatment creates additional cost and resource impacts for DHB services. PHARMAC provided estimates of these impacts when consulting on the proposal, to help DHBs with planning. 

Concern that there will be additional costs associated with updating clinical pathways and educational materials for healthcare professionals and patients.

There will be some costs to DHBs to update existing resources that discuss rituximab by brand name. We intend to discuss this issue further with DHBs through our implementation activities to explore how we can support this.

Concern about the logistical requirements for pharmacy to review prescribing, dispensing and ordering systems required for the requirement of having two brands of rituximab.

 

We agree there will need to be good systems in place to manage different brands for separate indications. PHARMAC intends to work with DHBs where possible to support any work required to address this, particularly regarding how the rituximab changes are made in PHARMAC systems (Schedule listing, Special Authority naming) and how these are communicated. PHARMAC will be organising a working group with DHB staff to develop resources to support the change. However, PHARMAC consider it will be up to individual DHBs to make their own system decisions.

If you have any questions about this decision, you can email us at enquiry@pharmac.govt.nz; or call our toll free number (9 am to 5 pm, Monday to Friday) on 0800 66 00 50.