Proposal to fund vedolizumab for inflammatory bowel disease and brentuximab for rare lymphomas

Medicines Consultation Closed

What we're proposing

We are seeking feedback on a proposal to fund two new treatments: vedolizumab for inflammatory bowel disease and brentuximub for rare lymphomas. In summary: 

  • vedolizumab (brand name Entyvio) would be funded for the treatment of people with inflammatory bowel disease (ulcerative colitis or Crohn’s disease) that has not responded to prior treatments, from 1 February 2023 
  • brentuximab vedotin (brand name Adcetris) would be funded for the treatment of people with Hodgkin and anaplastic large cell lymphoma that has relapsed or not responded to treatment, at a date to be determined following Medsafe approval. Prior to Medsafe approval, Pharmac would create a mechanism to consider funding applications for brentuximab vedotin (Adcetris) via our Exceptional Circumstances Framework for people who meet the proposed eligibility criteria.

The provisional agreement with the supplier of vedolizumab and brentuximab, Takeda New Zealand Limited (Takeda), also includes a price reduction for a currently funded treatment for hereditary angioedema, icatibant (Firazyr).

This proposal would not prevent Pharmac from funding additional treatment options for patients with IBD or rare lymphomas. We are still considering the funding of these other treatments.

Further details on this proposal, including how to provide feedback, can be found below.

We welcome your feedback on this proposal. Consultation closes at 4 pm on Wednesday, 5 October 2022 and feedback can be emailed to consult@pharmac.govt.nz.

Vedolizumab for inflammatory bowel disease

What would the effect be?

From 1 February 2023 vedolizumab (Entyvio) would be funded for people with ulcerative colitis or Crohn’s disease that has not responded to, or are intolerant of, conventional therapies and/or anti-tumour necrosis factor (TNF) alpha therapy (ie adalimumab and infliximab, subject to eligibility criteria.

Our clinical advisors have told us that evidence suggests that vedolizumab offers clinically significant health benefit in terms of response and remission in patients with these conditions, which are forms of inflammatory bowel disease (IBD).

We estimate that approximately 450 people with IBD would benefit in the first year increasing up to 1200 people after a few years.

We are unsure of the relative proportion of Māori or Pacific people that would benefit from treatment, as there is an absence of data on the prevalence of moderate-to-severe IBD in these populations. The advice we have received suggests that Māori and Pacific people make up a small but increasing proportion of all IBD cases.

Who we think will be interested

  • People with IBD and their whānau, and caregivers
  • Gastroenterologists, specialist nurses, and other health professionals involved in the care of people with IBD.
  • Hospital and community pharmacists, Te Whatu Ora and wholesalers
  • Pharmaceutical suppliers
  • Other organisations with an interest in IBD and its treatment

About inflammatory bowel disease

IBD is a chronic inflammatory condition of the gastrointestinal tract. It encompasses two types of intestinal disease, Crohn’s disease and ulcerative colitis. These conditions are differentiated by the location of intestinal inflammation, as well as the depth of involvement of the bowel wall.

In Crohn’s disease, inflammation can occur in any part of the gastrointestinal tract, tends to have a patchier distribution, and can penetrate deep into the bowel wall, causing abscesses and fistulae. In contrast, inflammation in ulcerative colitis is typically confined to the large colon, is more continuous in its presentation, and impacts the top layers of the bowel wall.

Both conditions are characterised by a relapsing and remitting pattern of symptoms which commonly include diarrhoea, abdominal pain and cramping, blood in the stool, reduced appetite, weight loss and fatigue. In some patients with IBD, inflammation can also extend beyond the bowel and include dermatological, ophthalmic, musculoskeletal, and renal involvement.

While the management of IBD is individualised, periods of relapse are typically treated with conventional therapies such as immunosuppressants and glucocorticoids, followed by anti-TNF agents. In some patients, IBD requires surgical management.

About vedolizumab

For patients that have experienced a loss of response to conventional therapies and/or anti-TNF agents, vedolizumab offers an alternative method of action to control periods of intestinal inflammation.

Vedolizumab is a humanised monoclonal antibody (ie biologic therapy) which selectively binds to immune cells that are unique to the gastrointestinal tract involved in the characteristic inflammation seen in IBD. By binding to these immune cells, vedolizumab selectively interrupts the inflammatory processes that cause IBD.

Vedolizumab has recently received Medsafe approval(external link) for:

  • the treatment of adult patients with moderate to severe ulcerative colitis who have had an inadequate response with, or lost response to, either conventional therapy or anti-TNF therapy, or for whom this treatment is not tolerated 
  • the treatment of adult patients with moderate to severe Crohn's disease who have had an inadequate response with, or lost response to, either conventional therapy or anti-TNF therapy or for whom this treatment is not tolerated. 

Vedolizumab is not registered for treatment of adolescents and children below the age of 18. The paediatric criteria for Crohn’s disease in this proposal reflect the advice that we have received from our advisors that separate criteria would be preferable for those aged 18 and below given the differences in the disease activity scoring indices between the age groups. 

Vedolizumab is administered as an intravenous infusion at 0, 2 and 6 weeks and then every 8 weeks thereafter at a flat dose of 300mg over 30 minutes. Our advisors have told us that funding vedolizumab would lead to a reduction in overall hospital infusion hours given the shorter infusion time compared with infliximab.

Why we’re proposing this

A funding application for vedolizumab for the treatment of ulcerative colitis and Crohn’s disease was reviewed by Pharmac’s Gastrointestinal Subcommittee (now Gastrointestinal Advisory Committee) in April 2017(external link) and it recommended that vedolizumab be funded with a high priority(external link) for patients that have not experienced response to infliximab or adalimumab; and if cost-neutral(external link) to the currently listed anti-TNF agents in patients that that do not respond to conventional therapy.

Pharmac’s Pharmacology and Therapeutics Advisory Committee (PTAC) reviewed this funding application in November 2020(external link) and recommended that vedolizumab funded with a high priority(external link) for the treatment of patients who have either had failure of, become refractory to, or experienced severe and intractable side effects from anti-TNF agents. PTAC also recommended that vedolizumab be funded in patients that that have experienced non-response or intolerance to conventional therapy with a medium priority(external link) in the setting of ulcerative colitis and if cost-neutral(external link) to anti-TNF agents in the setting of Crohn’s disease.

Our advisors have told us that there is a need for additional funded biologic therapies for patients with IBD and that vedolizumab offers clinical benefit for these patients in terms of disease response and remission.

We have now reached an agreement with the supplier, Takeda, to fund vedolizumab for patients in Aotearoa New Zealand.

Enabling clinician and patient choice

We are proposing to fund vedolizumab for patients whose disease has not responded to or who are intolerant of conventional therapy, to enable clinician and patient choice earlier in the treatment paradigm for IBD. This approach would enable clinicians and patients to choose the biological therapy that best meets the patient’s circumstances, and aligns with the advice that we have received that vedolizumab is a safe and effective therapy in both anti-TNF naïve and experienced patients.

Details about our proposal

Vedolizumab (Entyvio) would be listed in Section B and Part II of Section H of the Pharmaceutical Schedule from 1 February 2023 at the following prices and subsidies (ex-manufacturer, excluding GST):

Chemical

Formulation

Brand

Pack size

Price and subsidy

Vedolizumab

Inj 300 mg vial

Entyvio

1

$3,313.00

A confidential rebate would apply to vedolizumab (Entyvio) that would reduce the net price to the Funder. Entyvio would have protection from delisting and subsidy reduction until 01 February 2026.

Entyvio would be listed as a PCT only pharmaceutical in Section B of the Pharmaceutical Schedule, meaning that only DHB hospitals would be able to make a subsidy claims.

Crohn’s disease

Entyvio would be listed in Section B and Part II of Section H subject to the following eligibility criteria:

Special Authority for Subsidy/Hospital Indication Restrictions

Initial application – (Crohn’s disease – Adult) from any relevant practitioner. Approvals valid for 6 months for application meeting the following criteria:

All of the following:

  1. Patient has active Crohn’s disease; and
  2. Any of the following:
    1. Patient has a CDAI score of greater than or equal to 300, or HBI score of greater than or equal to 10; or
    2. Patient has extensive small intestine disease affecting more than 50 cm of the small intestine; or
    3. Patient has evidence of short gut syndrome or would be at risk of short gut syndrome with further bowel resection; or
    4. Patient has an ileostomy or colostomy, and has intestinal inflammation; and
  3. Patient has tried but had an inadequate response to, or has experienced intolerable side effects from, prior therapy with immunomodulators (unless contraindicated) and corticosteroids; and
  4. Surgery (or further surgery) is considered to be clinically inappropriate.

Renewal – (Crohn’s disease – Adult) any relevant practitioner. Approvals valid for 6 months for application meeting the following criteria:

Both:

  1. Any of the following:
    1. CDAI score has reduced by 100 points, or HBI score has reduced by 3 points, from when the patient was initiated on vedolizumab; or
    2. CDAI score is 150 or less, or HBI is 4 or less; or
    3. The patient has demonstrated an adequate response to treatment, but CDAI score and/or HBI score cannot be assessed; and
  2. Vedolizumab to administered at a dose no greater than 300 mg every 8 weeks. 

Initial application – (Crohn’s disease – children*) any relevant practitioner. Approvals valid for 6 months for application meeting the following criteria:

All of the following:

  1. Paediatric patient has active Crohn’s disease; and
  2. Either:
    1. Patient has a Paediatric Crohn’s Disease Activity Index (PCDAI) score of greater than or equal to 30; or
    2. Patient has extensive small intestine disease; and
  3. Patient has tried but had an inadequate response to, or has experienced intolerable side effects from, prior therapy with immunomodulators and corticosteroids; and
  4. Surgery (or further surgery) is considered to be clinically inappropriate.

Note: Indication marked with * is an unapproved indication

Renewal – (Crohn’s disease – children*) any relevant practitioner. Approvals valid for 6 months for application meeting the following criteria:

Both:

  1. Any of the following:
    1. PCDAI score has reduced by 10 points from when the patient was initiated on vedolizumab; or
    2. PCDAI score is 15 or less; or
  2. The patient has demonstrated an adequate response to treatment, but CDAI score cannot be assessed; and
  3. Vedolizumab to administered at a dose no greater than 300mg every 8 weeks.

Note: Indication marked with * is an unapproved indication

Ulcerative colitis

Entyvio would be listed in Section B and Part II of Section H subject to the following eligibility criteria:

Initial application – (ulcerative colitis) from any relevant practitioner. Approvals valid for 6 months for application meeting the following criteria:

All of the following:

  1. Patient has histologically confirmed ulcerative colitis; and
  2. Either
    1. Patient has a SCCAI score is greater than or equal to 4; or
    2. Patient’s PUCAI score is greater than or equal to 65*; and
  3. Patient has tried but had an inadequate response to, or has experienced intolerable side effects from, prior therapy with immunomodulators and corticosteroids; and
  4. Surgery (or further surgery) is considered clinically inappropriate.
  5. Note: Indication marked with * is an unapproved indication

Renewal – (moderate to severe ulcerative colitis) from any relevant practitioner. Approvals valid for 6 months for application meeting the following criteria:

Both:

  1. Either
    1. The SCCAI score has reduced by 2 points or more from the SCCAI score since initiation on vedolizumab; or
    2. The PUCAI score has reduced by 30 points or more from the PUCAI score since initiation on vedolizumab*; and
  2. Vedolizumab will be used at a dose no greater than 300 mg intravenously every 8 weeks. 

Note: Indication marked with * is an unapproved indication

Other treatments for inflammatory bowel disease

We understand that there would remain a clinical need for additional funded treatment options for patients with IBD. This proposal would not prevent Pharmac from considering the funding of these. 

We currently have active funding applications for the biologic therapy ustekinumab for the treatment of patients with Crohn’s disease(external link) or ulcerative colitis(external link). These applications have been ranked on the Options for Investment list. We are still considering the funding of ustekinumab and are in conversation with the supplier. 

We also have also received a funding application for the small molecule upadacitinib for the treatment of ulcerative colitis(external link). The Gastrointestinal Advisory Committee considered this funding application at their August meeting and the record of this meeting is currently in development.

Brentuximab vedotin for the treatment of Hodgkin and anaplastic large-cell lymphoma

What would the effect be?

Following Medsafe approval, Brentuximab vedotin would be listed on the Pharmaceutical Schedule, subject to eligibility criteria, for the treatment of:

  • relapsed or refractory Hodgkin lymphoma after, or for those that are ineligible for, autologous stem cell transplant; and
  • CD30-positive systemic anaplastic large-cell lymphoma

We estimate that approximately 20-30 people with relapsed or refractory Hodgkin or anaplastic large cell lymphoma would benefit from treatment each year.

We are unsure of the relative proportion of Māori or Pacific people that would benefit from treatment, as there is an absence of data due to the rarity of these cancers and the size of the patient group expected to be eligible for treatment.

Who we think will be interested

  • People with lymphoma and their whānau and caregivers
  • Oncologists, specialist nurses, and other health professionals involved in the care of people with Hodgkin’s or anaplastic large cell lymphoma
  • Hospital and community pharmacists, Te Whatu Ora and wholesalers
  • Pharmaceutical suppliers
  • Other organisations with an interest in the treatment of lymphoma

About Hodgkin and anaplastic large cell lymphoma

Hodgkin lymphoma is a cancer of the lymphatic system (a part of the immune system), and mainly affects the lymphocytes. People with relapsed or refractory disease are those who have not benefitted from treatment or have deteriorated after a response to chemotherapy. They typically go on to be treated with further chemotherapy and, if eligible, autologous stem cell transplant, which is curative approximately half of the time. For those patients with relapsed or refractory Hodgkin lymphoma that are ineligible to receive, or have already received, an autologous stem cell transplant, there are currently limited treatment options.

Anaplastic large cell lymphoma is a rare type of non-Hodgkin lymphoma. People with relapsed or refractory anaplastic large cell lymphoma are those who have not benefitted from or relapsed after chemotherapy. They typically receive a second line of chemotherapy and an autologous stem cell transplant if eligible, however, their prognosis is poor.

About brentuximab vedotin

Brentuximab vedotin is a targeted cancer therapy. Targeted cancer therapies work by ‘targeting’ the changes in cancer cells that help a cancer cell to survive and multiply within the body. Brentuximab vedotin is made up of a monoclonal antibody (brentuximab) that recognises the CD30 cell surface antigen, attached to a chemotherapy agent (vedotin). Brentuximab vedotin binds to the CD30 receptor of CD30-positive cancer cells where it is internalised. Within the cancer cell, the chemotherapeutic agent is released resulting in cell death.

Brentuximab vedotin is administered as an intravenous infusion at a dose of 1.8mg/kg over 30 minutes every 3 weeks.

Our advisors have told us that brentuximab vedotin increases the likelihood of remission and reduces the likelihood of progression or death.

Why we’re proposing this

A funding application for brentuximab vedotin for the treatment of relapsed or refractory Hodgkin’s and anaplastic large-cell lymphoma was reviewed by our Cancer Treatment Subcommittee (now called Cancer Treatments Advisory Committee) in September 2018 [PDF, 692 KB], which recommended funding brentuximab vedotin for:

The Pharmacology and Therapeutics Advisory Committee (PTAC noted) and agreed with these recommendations in February 2019 [PDF, 796 KB].

We have now reached an agreement with the supplier, Takeda, to fund brentuximab vedotin for patients in Aotearoa New Zealand.

Details about our proposal

Brentuximab vedotin (Adcetris) would be listed in Section B and Part II of Section H of the Pharmaceutical Schedule as soon as practicable following Medsafe approval at the following prices and subsidies (ex-manufacturer, excluding GST): 

Chemical

Formulation

Brand

Pack size

Price and subsidy

Brentuximab vedotin

Inj 50 mg vial

Adcetris

1

$5,275.18

A confidential rebate would apply to Adcetris that would reduce the net price to the Funder. Adcetris would have protection from delisting and subsidy reduction until 1 December 2025.

This proposal would not prevent Pharmac from considering the funding of additional therapies for patients with rare lymphomas.

Adcetris would be listed as a PCT only pharmaceutical in Section B of the Pharmaceutical Schedule, meaning that only DHB hospitals would be able to make a subsidy claims.

Adcetris would be listed in Section B and Part II of Section H subject to the following eligibility criteria:

Special Authority for Subsidy/Hospital Indication Restrictions

Initial application - (relapsed/refractory Hodgkin lymphoma) from any relevant practitioner. Approvals valid for 6 months for applications meeting the following criteria:

All of the following:

  1. Either:
    1. Both:
      1. Patient has relapsed/refractory CD30-positive Hodgkin’s lymphoma after two or more lines of chemotherapy; and
      2. Patient is ineligible for autologous stem cell transplant; or
    2. Both:
      1. Patient has relapsed/refractory CD30-positive Hodgkin’s lymphoma; and
      2. Patient has previously undergone autologous stem cell transplant; and
  2. Patient has not previously received funded brentuximab vedotin; and
  3. Response to brentuximab vedotin treatment is to be reviewed after a maximum of 6 treatment cycles; and
  4. Brentuximab vedotin to be administered at doses no greater than 1.8 mg/kg every 3 weeks. 

Renewal - (relapsed/refractory Hodgkin lymphoma) - from any relevant practitioner. Approvals valid for 9 months for applications meeting the following criteria:

All of the following:

  1. Patient has achieved a partial or complete response to brentuximab vedotin after 6 treatment cycles; and
  2. Treatment remains clinically appropriate and the patient is benefitting from treatment and treatment is being tolerated; and
  3. Patient is to receive a maximum of 16 total cycles of brentuximab vedotin treatment.

Initial application - (anaplastic large cell lymphoma) - from any relevant practitioner. Approvals valid for 6 months for applications meeting the following criteria:

All of the following:

  1. Patient has relapsed/refractory CD30-positive systemic anaplastic large cell lymphoma; and
  2. Patient has an ECOG performance status of 0-1; and
  3. Patient has not previously received brentuximab vedotin; and
  4. Response to brentuximab vedotin treatment is to be reviewed after a maximum of 6 treatment cycles; and
  5. Brentuximab vedotin to be administered at doses no greater than 1.8 mg/kg every 3 weeks. 

Renewal - (anaplastic large cell lymphoma) - from any relevant practitioner. Approvals valid for 9 months for applications meeting the following criteria:

All of the following:

  1. Patient has achieved a partial or complete response to brentuximab vedotin after 6 treatment cycles; and
  2. Treatment remains clinically appropriate and the patient is benefitting from treatment and treatment is being tolerated; and
  3. Patient is to receive a maximum of 16 total cycles of brentuximab vedotin treatment.

Enabling applications via our Exceptional Circumstances Framework prior to Medsafe approval

If the proposal to fund brentuximab vedotin subject to Medsafe registration is approved, we would look to establish a simple pathway under our Exceptional Circumstances Framework to consider applications for funded access to brentuximab vedotin prescribed and used in accordance with Section 29 of the Medicines Act 1981(external link) for patients who consent to treatment and meet eligibility criteria, from 1 December 2022 until brentuximab vedotin is listed on the Pharmaceutical Schedule. 

This would enable funded access to Adcetris prior to Medsafe approval for a small group of patients with a high unmet health need. We would provide details of this process at the same time as we notify a positive funding decision. 

Other changes associated with this proposal

Icatibant

Icatibant is funded for the treatment of hereditary angioedema, a rare disease that can present as attacks of swelling that can occur anywhere in the face, larynx (throat), gut or limbs.

As part of this proposal, the net price for Icatibant (Firazyr) would reduce via confidential rebate from 1 December 2022 and Firazyr would have protection from delisting and subsidy reduction until 1 December 2024.

There would be no changes to the current eligibility criteria for Firazyr as part of this proposal.

To provide feedback

Send us an email: consult@pharmac.govt.nz by 4pm on Wednesday, 5 October 2022.

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). Please be aware that we may need to share your feedback, including your identity, in response to an OIA request. This applies to anyone providing feedback, whether they are providing feedback themselves or for an organisation, in a personal or professional capacity.

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