Decision to list enzyme replacement therapies for some rare disorders

Medicines Decision

PHARMAC is pleased to announce the approval of an agreement with Sanofi-Aventis New Zealand Limited (trading as Sanofi-Genzyme) for the listing of alglucosidase alfa (Myozyme), idursulfase (Elaprase), and laronidase (Aldurazyme) for rare enzyme deficiency disorders.

The agreement is the sixth that PHARMAC has reached with a bidder in a Request for Proposals we ran in 2014, related to the supply of medicines for rare disorders. This was the subject of a consultation letter dated 17 October 2016.

In summary, the effect of the decision is that the following three enzyme replacement therapies will be funded in the community under Special Authority criteria and in DHB hospitals, subject to restrictions, for the following indications and listing dates:

  • alglucosidase alfa (Myozyme) for patients with infantile Pompe disease, from 1 December 2016;
  • idursulfase (Elaprase) for patients with Hunter syndrome receiving a haematopoietic stem cell transplant, from 1 December 2016, and
  • laronidase (Aldurazyme) for patients with Hurler syndrome receiving a haematopoietic stem cell transplant. Listing in the Pharmaceutical Schedule would occur following Medsafe approval of the pharmaceutical.

The decision is as consulted on, with the exception of some changes to the alglucosidase alfa renewal criteria. 

Details of the decision

Alglucosidase alfa for infantile Pompe disease

From 1 December 2016, alglucosidase alfa (Myozyme) will be listed in Section B (the Community) and Part II of Section H (the Hospital Medicines List, HML) of the Pharmaceutical Schedule as follows:

Chemical

Presentation

Brand

Pack size

Price and subsidy

Alglucosidase alfa

Inj 50 mg vial

Myozyme

1

$1,142.60
  • Alglucosidase alfa will be listed subject to the following Special Authority criteria in the community and equivalent restrictions in the HML:

Special Authority for Subsidy

Initial application only from a metabolic physician.  Approvals valid for 12 months for applications meeting the following criteria:

All of the following:

  1. The patient is aged up to 24 months at the time of initial application and has been diagnosed with infantile Pompe disease; and
  2. Any of the following:
    1. Diagnosis confirmed by documented deficiency of acid alpha-glucosidase by prenatal diagnosis using chorionic villus biopsies and/or cultured amniotic cells; or
    2. Documented deficiency of acid alpha-glucosidase, and urinary tetrasaccharide testing indicating a diagnostic elevation of glucose tetrasaccharides; or
    3. Documented deficiency of acid alpha-glucosidase, and documented molecular genetic testing indicating a disease-causing mutation in the acid alpha-glucosidase gene (GAA gene); or
    4. Documented urinary tetrasaccharide testing indicating a diagnostic elevation of glucose tetrasaccharides, and molecular genetic testing indicating a disease-causing mutation in the GAA gene; and
  3. Patient has not required long-term invasive ventilation for respiratory failure prior to starting enzyme replacement therapy (ERT); and
  4. Patient does not have another life-threatening or severe disease where the prognosis is unlikely to be influenced by ERT or might be reasonably be expected to compromise a response to ERT; and
  5. Alglucosidase alfa to be administered at doses no greater than 20 mg/kg every 2 weeks.

Renewal only from a metabolic physician. Approvals valid for 12 months for applications meeting the following criteria:

All of the following:

  1. The treatment remains appropriate for the patient and the patient is benefiting from treatment; and
  2. Alglucosidase alfa to be administered at doses no greater than 20 mg/kg every 2 weeks; and
  3. Patient has not had severe infusion-related adverse reactions which were not preventable by appropriate pre-medication and/or adjustment of infusion rates; and
  4. Patient has not developed another life threatening or severe disease where the long term prognosis is unlikely to be influenced by ERT; and
  5. Patient has not developed another medical condition that might reasonably be expected to compromise a response to ERT; and
  6. There is no evidence of life threatening progression of respiratory disease as evidenced by the need for >14 days of invasive ventilation; and
  7. There is no evidence of new or progressive cardiomyopathy.

Idursulfase for Hunter Syndrome

From 1 December 2016, idursulfase (Elaprase) will be listed in Section B (the Community) and Part II of Section H (the Hospital Medicines List, HML) of the Pharmaceutical Schedule as follows:

Chemical Presentation Brand Pack size Price and subsidy
Idursulfase Inj 2 mg per ml, 3 ml vial Elaprase 1 $4,608.30
  • Idursulfase will be listed subject to the following Special Authority criteria in the community and equivalent restrictions in the HML:

Special Authority for Subsidy

Initial application only from a metabolic physician.  Approvals valid for 24 weeks for applications meeting the following criteria:

All of the following:

  1. The patient has been diagnosed with Hunter Syndrome (mucopolysaccharidosis II); and
  2. Either:
    1. Diagnosis confirmed by demonstration of iduronate 2-sulfatase deficiency in white blood cells by either enzyme assay in cultured skin fibroblasts; or
    2. Detection of a disease causing mutation in the iduronate 2-sulfatase gene; and
  3. Patient is going to proceed with a haematopoietic stem cell transplant (HSCT) within the next 3 months and treatment with idursulfase would be bridging treatment to transplant; and
  4. Patient has not required long-term invasive ventilation for respiratory failure prior to starting Enzyme Replacement Therapy (ERT); and
  5. Idursulfase to be administered for a total of 24 weeks (equivalent to 12 weeks pre- and 12 weeks post-HSCT) at doses no greater than 0.5 mg/kg every week.

Laronidase for Hurler Syndrome

Following Medsafe approval, laronidase (Aldurazyme) will be listed in Section B (the Community) and Part II of Section H (the Hospital Medicines List, HML) of the Pharmaceutical Schedule as follows:

Chemical Presentation Brand Pack size Price and subsidy
Laronidase Inj 100 U per ml, 5 ml vial Aldurazyme 1 $1,335.16
  • Laronidase will be listed as soon as reasonably practicable following Sanofi- Genzyme’s notification to PHARMAC that Medsafe has granted registration.
  • Laronidase will be listed subject to the following Special Authority criteria in the community and equivalent restrictions in the

Special Authority for Subsidy

Initial application only from a metabolic physician.  Approvals valid for 24 weeks for applications meeting the following criteria:

All of the following:

  1. The patient has been diagnosed with Hurler Syndrome (mucopolysacchardosis I-H); and
  2. Either:
    1. Diagnosis confirmed by demonstration of alpha-L-iduronidase deficiency in white blood cells by either enzyme assay in cultured skin fibroblasts; or
    2. Detection of two disease causing mutations in the alpha-L-iduronidase gene and patient has a sibling who is known to have Hurler syndrome; and
  3. Patient is going to proceed with a haematopoietic stem cell transplant (HSCT) within the next 3 months and treatment with laronidase would be bridging treatment to transplant; and
  4. Patient has not required long-term invasive ventilation for respiratory failure prior to starting Enzyme Replacement Therapy (ERT); and
  5. Laronidase to be administered for a total of 24 weeks (equivalent to 12 weeks pre- and 12 post-HSCT) at doses no greater than 100 units/kg every week.
  • Prior to a listing on the Pharmaceutical Schedule (i.e. until Medsafe approval is granted and the listing has been implemented) the above list price will apply to any individual patient funding applications approved via the Named Patient Pharmaceutical Assessment (NPPA) Policy.

Feedback received

We appreciate all of the feedback that we received and acknowledge the time people took to respond. All consultation responses received by 1 November 2016 were considered in their entirety in making a decision on the proposed changes. All responses were supportive of the proposal, and the following issues were raised in relation to specific aspects of the proposal:

Theme

Comment

Alglucosidase alfa for infantile Pompe disease

Infantile Pompe disease is a devastating condition with high mortality if untreated. Early treatment with alglucosidase alfa can be life-saving and prevent muscle damage. This not only impacts the patient but also their parents and families. A number of respondents provided detail of their own personal experience with the disease.

PHARMAC appreciates the significant amount of consultation feedback received from people who have Pompe disease and their families, and in particular their candor and honesty about how Pompe disease has impacted them and their families.

Alglucosidase alpha would be a difficult treatment to start. Would support use of a Panel of clinicians that determines use (such as the Gaucher Panel).

Noted. We also appreciate the difficult situation clinicians are in regarding the complex decisions that are needed to start treatment. In this case, due to the very low expected number of patients with Infantile Pompe disease we consider it would be manageable via a standard Special Authority process.

Concerns that the criteria are too loose, particularly renewal criterion 6. Expect that patients will decline to some degree, but there is a huge difference between being ambulatory and requiring ventilation. Cardiomyopathy is a sign that treatment is not working. The heart and breathing are the most important indicators of disease progression or poor response, much more so than physical development.

The Special Authority and HML renewal criterion 6 has been amended in light of the feedback as follows:

  1. There is no evidence of life threatening progression of respiratory disease as evidenced by the need for >14 days of invasive ventilation; and
  2. There is no evidence of new or progressive cardiomyopathy.

PHARMAC considers the changes more clearly set out the intent of criteria and would ensure that ongoing funded is targeted to patients that are responding to treatment.

Is there a definition of “life-threatening or severe disease” as it would apply in criterion 4 of the Special Authority? Considered it would be inappropriate and unfair to limit treatment for budgetary reasons, rather than clinical reasons.

The Special Authority (SA) criteria are based on the Australian Life Saving Drug Programme (LSDP) criteria. The role of SA criteria is to target treatment to those patients that would benefit most from treatment, and this includes managing the overall cost of treatment.

Noted ERT works differently for everyone and slowing progression of disease is still a very good outcome.

Noted. The SA criteria have been amended following consideration of consultation feedback to more clearly indicate the intent of the renewal criteria with regard to disease progression.

Noted that the best way to diagnose Pompe disease is through blood spot testing. It could be included in the standard Guthrie card for newborn screening. Muscle biopsies are often inclusive or incorrect.

The diagnostic criteria included in the Special Authority are derived from the Australian LSDP criteria and based on current available diagnostic testing for Pompe disease. We note newborn screening for Infantile Pompe disease is not currently included in the NZ screening programme. However, the SA criteria could be reviewed in the future if newborn screening for lysosomal diseases was implemented in NZ. 

Noted an application for Late-Onset Pompe disease (LOPD) is being considered for funding. Questioned where Juvenile Pompe disease fits within LOPD and this proposal for funding treatment for infantile disease.

Juvenile Pompe disease is a sub-group of LOPD. In the Australian LSDP criteria, juvenile disease is separated out from infantile Pompe disease and LOPD. However in the NZ context, LOPD would include any patient diagnosed after the age of 1 year who does not meet the eligibility criteria for infantile Pompe disease funding.

Concerns regarding the small number of Metabolic Physicians in New Zealand, and that restricting the Special Authority to Metabolic Physicians only would limit and delay access to treatment with alglucosidase alfa. Considered other specialists (eg neurologists) should be able to initiate and review treatment. 

PHARMAC considers that Metabolic Physicians from the National Metabolic Service (NMS) are best placed to initiate enzyme replacement therapy for infantile Pompe disease. The NMS is based at Starship Children’s Health and provides a national service for all children with metabolic conditions, with regional clinics and teleconference support in place. The NMS would be involved in any discussions to start or stop treatment with alglucosidase alfa for infantile Pompe disease across the country.

We note that any prescriber could write repeat prescriptions for alglucosidase alfa, however a Metabolic Physician would need to apply for a Special Authority renewal annually. We note these applications can be made electronically. Clinician feedback was supportive of this requirement and considered it was appropriate.

PHARMAC notes it may be possible to review this restriction sometime in the future if there is increased awareness of infantile Pompe disease amongst specialist paediatricians.

We note that patients with LOPD may have other specialists as their lead clinician and, the application for funding of alglucosidase alfa for patients with LOPD would not necessarily result in the same access criteria as have been decided for infantile Pompe disease.

A positive step forward for infantile Pompe disease patients.

Concerns that there is still a large inequitable gap for the 10 adult patients living with Pompe disease in New Zealand who do not have access to funded treatment. Noted treatment is funded in 76 other countries for LOPD.

Patients with LOPD should also receive funded treatment. Noted recent evidence that has been published regarding LOPD.

 

PHARMAC appreciates there is a strong desire for funding of alglucosidase alfa to be extended to patients with LOPD.

We note that PTAC has assessed alglucosidase alfa for patients with LOPD a number of times, and on each occasion has recommended the application be declined. PHARMAC continues to review new evidence as it comes to hand and discuss the funding option with the supplier.  In May 2016 PHARMAC received a Schedule funding application from Sanofi Genzyme for alglucosidase alfa for LOPD. This application is due to be considered by PTAC in November 2016 and remains under consideration. Information about the application can be found on PHARMAC’s Application Tracker here(external link) and it will be updated with links to PTAC minutes when these are available.

Idursulfase for Hunter Syndrome & laronidase for Hurler Syndrome

What about patients where transplant cannot be performed or transplant is not successful?

Noted patients with the Hurler-Sheie variant of MPS-I are not eligible for treatment.

Would these patients be eligible for funding via NPPA?

 

Patients with Hunter syndrome or Hurler syndrome who do not receive a transplant, or where transplant has been unsuccessful, and patients with the Hurler-Sheie variant of MPS-I would not be eligible for funded ERT via this decision.

 

PHARMAC has considered funding applications for ERT for these indications, and PTAC has previously recommended the applications for funding  ERT for these conditions be declined, so it seems unlikely that any application for funding via NPPA would meet the core principles of the NPPA Policy. 

More information

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.