Proposal to list enzyme replacement therapies for some rare disorders

Medicines Consultation Closed

PHARMAC is seeking feedback on a proposal to list alglucosidase alfa (Myozyme), idursulfase (Elaprase), and laronidase (Aldurazyme) for rare enzyme deficiency disorders, resulting from a provisional agreement formed between Sanofi-Aventis New Zealand Limited (trading as Sanofi-Genzyme) and PHARMAC.

The provisional 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.

In summary, this proposal would result in three enzyme replacement therapies being funded in the community under Special Authority criteria and in DHB hospitals subject to restrictions for the following indications:

  • 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.

Feedback sought

PHARMAC welcomes feedback on this proposal. To provide feedback, please submit it in writing by 5pm Tuesday, 1 November 2016 to:

Caroline De Luca
Senior Therapeutic Group Manager / Team Leader
PHARMAC
PO Box 10 254
Wellington 6143

Email: caroline.deluca@pharmac.govt.nz

Fax:     04 460 4995

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. 

Details of the proposal

Alglucosidase alfa for infantile Pompe disease

From 1 December 2016, alglucosidase alfa (Myozyme) would 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 would 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 disease progression with regular therapy, including but not limited to the development of the need for 24 hour invasive ventilation for 14 days or greater for irreversible and progressive cardiorespiratory failure.

Idursulfase for Hunter Syndrome

From 1 December 2016, idursulfase (Elaprase) would 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 would 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: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
    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 has not required long-term invasive ventilation for respiratory failure prior to starting Enzyme Replacement Therapy (ERT); and
  4. 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.
  • Treatment would be limited to a total duration of 24 weeks around the time of haematopoietic stem cell transplant (HSCT).

Laronidase for Hurler Syndrome

Following Medsafe approval, laronidase (Aldurazyme) would 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 would be listed as soon as reasonably practicable following Sanofi - Genzyme’s - notification to PHARMAC that Medsafe has granted registration.
  • Laronidase would 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 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.
  • Treatment would be limited to a total of 24 weeks duration around the time of haematopoietic stem cell transplant (HSCT).
  • Prior to a listing on the Pharmaceutical Schedule (i.e. until Medsafe approval is granted and the listing has been implemented) the proposed list price would apply to any individual patient funding applications approved via the Named Patient Pharmaceutical Assessment (NPPA) Policy.

Background

PHARMAC’s evaluation of Aldurazyme, Elaprase and Myozyme followed the process described in Schedule 2 of the Request for Proposals (RFP) for the supply of medicines for rare disorders. 

There is still one more product in negotiation, and PHARMAC is looking to wrap up the RFP by the end of 2016; following this we will evaluate this pilot process.

Alglucosidase alfa for infantile Pompe disease

Alglucosidase alfa (Myozyme®) is used in the treatment of glycogen storage disease type 2 (Pompe) disease.  

The infantile form presents very soon after birth and has a very poor prognosis. Treatment of infantile Pompe disease with the enzyme replacement therapy (ERT) alglucosidase alfa has been shown to prolong life and reduce the need for mechanical ventilation.

This proposal is to list alglucosidase alfa for infantile Pompe disease with Special Authority criteria limiting treatment to those patients who are diagnosed prior to 24 months of age. Treatment would be ongoing unless a patient experienced serious adverse events from treatment or required long-term invasive ventilation.

Alglucosidase alfa is a hospital out-patient infusion treatment and is usually given as an intravenous infusion each fortnight; however, the proposal would include a listing in Section B of the Pharmaceutical Schedule to enable hospitals to claim the cost of the medicine from the CPB for out-patients.

Myozyme® is indicated for the long-term treatment of patients with a confirmed diagnosis of Pompe disease and is registered with Medsafe. We expect there would be less than 1 patient per year in New Zealand diagnosed with infantile Pompe disease and hence eligible for treatment. To date there have been no applications for ERT for the treatment of infantile Pompe disease through the NPPA process.

Earlier Schedule Funding assessments of alglucosidase alfa

In 2008, PHARMAC received its first Schedule funding application for alglucosidase alfa for Pompe disease from a clinician.  This was assessed by PTAC a number of times, and recommended for decline. More information regarding the application and links to previous PTAC minutes can be found on PHARMAC’s Application Tracker.

Separately, following an application for funding for an individual patient via its then exceptional circumstances scheme (now NPPA), in 2010 PHARMAC staff sought advice from PTAC on a proposal to list alglucosidase alfa for patients with late onset Pompe disease (LOPD). This was assessed by PTAC a number of times, and recommended for decline. More information regarding this application and links to previous PTAC minutes can be found on PHARMAC’s Application Tracker.

Recently, independent of the RFP process, PHARMAC has 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. PHARMAC continues to review new evidence as it comes to hand. This application can be found on PHARMAC’s Application Tracker here and it will be updated with links to PTAC minutes when these are available.

Idursulfase for Hunter syndrome

Idursulfase (Elaprase) is an ERT used in the treatment of the rare disorder mucopolysaccharidosis II (MPS II), otherwise known as Hunter Syndrome. Like other lysosomal storage disorders there is a disease continuum from mild to severe. Patients with more severe disease usually present at about 2 years of age. The disease can affect the heart, lungs, skeleton, brain, and spinal cord.

Elaprase is indicated for the long-term treatment of patients with Hunter syndrome and is registered with Medsafe.

Haematopoietic stem cell transplantation (HSCT) has been shown to be effective on the non-neurological symptoms of Hunter syndrome. Idursulfase can be used as an adjuvant treatment before HSCT to improve the pre-transplant clinical condition of the patient and assist in reducing the risk of transplant-related morbidity and mortality. The proposed Special Authority criteria would limit treatment to a maximum of 24 weeks around the time of transplant for patients with Hunter syndrome. The proposed criteria would be considered an off-label indication. 

Idursulfase is a hospital out-patient infusion treatment and is usually given as an intravenous infusion every week; however, the proposal would include a listing in Section B of the Pharmaceutical Schedule to enable hospitals to claim prescriptions from the CPB for out-patients.

PHARMAC estimates there would be up to one patient per year that would be eligible for idursulfase under the proposed criteria. To date, PHARMAC has received 2 NPPA applications for the funding of idursulfase for individuals with Hunter syndrome.   

Earlier Schedule Funding assessment of Idursulfase

In 2009, PHARMAC commenced assessment of several Enzyme Replacement Therapies, including idursulfase for the treatment of Mucopolysaccharidosis II (Hunter disease), for funding via the Pharmaceutical Schedule.   This was assessed by PTAC a number of times, and recommended for decline. More information regarding the application and links to previous PTAC minutes can be found on PHARMAC’s Application Tracker.

Laronidase for Hurler’s syndrome

Laronidase is an enzyme replacement therapy (ERT) used in the treatment of the rare disorder mucopolysaccharidosis I (MPS I). There are three variants of MPS I which differ in their severity, Hurler Syndrome (57% of MPS I patients) being the most severe, Scheie Syndrome (20%) being the mildest and Hurler-Scheie Syndrome (23%), being intermediate.

Hurler Syndrome is usually diagnosed at 6-8 months of age. It is associated with skeletal deformities and motor and intellectual impairment. Other manifestations include corneal clouding, organomegaly, short stature, heart disease, hernias, facial dysmorphism and hirsutism.

Medsafe approval for laronidase (Aldurazyme) lapsed in 2011. Sanofi-Aventis New Zealand Limited has resubmitted an application for registration to Medsafe and it is currently under assessment(external link). We note that internationally, Aldurzyme is indicated for the long-term treatment of patients with MPS 1 (Hurler syndrome) to treat the non-neurological manifestations of the disease.

Similar to Hunter Syndrome, HSCT has been shown to be effective and is the treatment of choice in more severely affected patients with Hurler Syndrome with neurological involvement. Treatment with ERT can slow progress but has no effect on neurological disease. Laronidase can be used as an adjuvant treatment before HSCT to improve the pre-transplant clinical condition of the patient and assist in reducing the risk of transplant-related morbidity and mortality. The proposed Special Authority criteria would limit treatment to a maximum of 24 weeks around the time of transplant for patients with Hurler syndrome. The proposed criteria would be considered an off-label indication. 

Laronidase is a hospital out-patient infusion treatment and is usually given as an intravenous infusion every week; however, the proposal would include a listing in Section B of the Pharmaceutical Schedule to enable hospitals to claim prescriptions from the CPB for out-patients.

PHARMAC estimates there would be up to one patient per year that would be eligible for laronidase under the proposed criteria. To date, PHARMAC has received 6 NPPA applications for the funding of idursulfase as a bridge to transplant for individuals with Hunter syndrome.   

Earlier Schedule Funding assessment of Laronidase

In 2009 PHARMAC commenced assessment of several Enzyme Replacement Therapies, including laronidase for the treatment of Mucopolysaccharidosis I (Hurler Syndrome), for funding via the Pharmaceutical Schedule.   This was assessed by PTAC a number of times, and recommended for decline. More information regarding the application and links to previous PTAC minutes can be found on PHARMAC’s Application Tracker.