Decision to list bedaquiline (Sirturo) and siltuximab (Sylvant) for rare disorders

Medicines

Decision

PHARMAC is pleased to announce the approval of an agreement with Janssen-Cilag Pty Ltd for the listing of bedaquiline (Sirturo) and siltuximab (Sylvant).

The agreement is the fourth that PHARMAC has reached with a bidder following 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 12 April 2016, available on PHARMAC’s website.

In summary, the effect of the decision is that:

  • bedaquiline (Sirturo) will be funded in the community and in DHB hospitals for treatment of extensively drug resistant tuberculosis (XDR-TB). Listing in the Pharmaceutical Schedule will occur subject to Medsafe approval of the pharmaceutical; and
  • siltuximab (Sylvant) will be funded in the community and in DHB hospitals for treatment of HHV-8 negative idiopathic multicentric Castleman’s disease (iMCD). This listing will occur from 1 June 2016.

The decision is as consulted on, with the exception of the following:

  • changes to the Special Authority/restriction applying to bedaquiline;
  • bedaquiline will be listed as XPharm; and
  • changes to the Special Authority/restriction applying to siltuximab.

Details of the decision

Bedaquiline (Sirturo)

Following Medsafe approval, bedaquiline (Sirturo) 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

Bedaquiline

Tab 100 mg

Sirturo

188

$24,162.00

  • Sirturo will be listed as soon as practicable following Janssen’s notification to PHARMAC that Medsafe has granted registration.
  • Sirturo will be listed XPharm in Section B of the Pharmaceutical Schedule meaning distribution will be arranged by PHARMAC and that community pharmacies will not be able to claim for this pharmaceutical. PHARMAC will undertake further consultation with relevant stakeholders on the most appropriate distribution mechanism for bedaquiline prior to the date bedaquiline is listed. There will also be no patient co-payment for bedaquiline as it is a treatment for tuberculosis.
  • Sirturo 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 from any relevant practitioner. Approvals valid for 6 months for applications meeting the following criteria:

Both:

  1. the patient has extensively drug-resistant tuberculosis (XDR-TB); and
  2. treatment with bedaquiline has been recommended by a multidisciplinary clinical team with expertise in the treatment of tuberculosis, with input from infectious disease and respiratory specialists.

Note: A recommendation from the Ministry of Health’s Tuberculosis Clinical Network would be sufficient to meet criterion 2 of the Special Authority.

  • Sirturo will have subsidy and delisting protection until 30 June 2018.
  • Prior to a listing on the Pharmaceutical Schedule (ie until Medsafe approval is granted) the list price will apply to any individual patient funding applications approved via the Named Patient Pharmaceutical Assessment (NPPA) Policy.

Siltuximab (Sylvant)

From 1 June 2016, siltuximab (Sylvant) will be listed in Section B (the Community) and Part II of Section H (the Hospital Medicines List) of the Pharmaceutical Schedule as follows:

Chemical

Presentation

Brand

Pack size

Price and subsidy

Siltuximab

Inj 100 mg vial

Sylvant

1

$770.57

Siltuximab

Inj 400 mg vial

Sylvant

1

$3,082.33

  • A confidential rebate will apply to Sylvant, which will reduce the net price of the treatment to the Funder.
  • Sylvant will be listed subject to the following Special Authority criteria in the community and equivalent restrictions in the Hospital Medicines List:

Special Authority for Subsidy

Initial application only from a haematologist or rheumatologist. Approvals valid for 6 months for applications meeting the following criteria:

All of the following:

1. Patient has severe HHV-8 negative idiopathic multicentric Castleman’s Disease; and

2. Treatment with an adequate trial ofcorticosteroids has proven ineffective; and

3. Siltuximab is to be administered at doses no greater than 11 mg/kg every 3 weeks.

Renewal only from a haematologist or rheumatologist. Approvals valid for 12 months where the treatment remains appropriate and the patient has sustained improvement in inflammatory markers and functional status.

The following note will apply to siltuximab in the Section B of the Pharmaceutical Schedule:

Note: Siltuximab is to be administered at doses no greater than 11 mg/kg every 3 weeks.

  • Sylvant will have Sole Supply Status in the community, Hospital Supply Status in DHB hospitals (DV limit 1%) and subsidy and delisting protection until 30 June 2018.
  • Prior to 1 June 2016, the contracted net pricing 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 12 April 2016 were considered in their entirety in making a decision on the proposed changes. Most responses were supportive of the proposal, and the following issues were raised in relation to specific aspects of the proposal:

Bedaquiline consultation feedback

Theme Comment
Supportive of access to bedaquiline for patients with XDR-TB. Noted.
Consideration should be given to providing bedaquiline for patients with multi-drug resistant tuberculosis (MDR-TB) as well as extensively drug-resistant tuberculosis (XDR-TB). This was considered by the Rare Disorders Subcommittee of PTAC at its November 2014 meeting and by the Anti-Infective Subcommittee of PTAC at its December 2015 meeting. The clinical advice PHARMAC received was that the indication should be restricted to those with XDR-TB. We note that PHARMAC could consider applications for patients with MDR-TB for whom bedaquiline may be indicated due to reasons such as intolerance to existing treatments via the NPPA Policy.
Patients should be managed via direct observed therapy (DOT). This falls within the remit of the Ministry of Health and DHB regional public health services, and is expected to be unaffected by this proposal.
Models of care and treatment support programmes for people with tuberculosis would need to offer a combination of different models according to local contexts. PHARMAC staff note this relates to the programmes that facilitate the administration of TB agents to patients (e.g. regional public health nurse supervision). This falls within the remit of the Ministry of Health and regional public health services, and is expected to be unaffected by this proposal.
Noted dosing and duration of treatment. A recent case report described continued safe use for 18 months. Noted. PHARMAC considers that, if funding treatment beyond 6 months is desired, this could be considered on a case by case basis via NPPA. PHARMAC notes that the number of patients likely to present in this situation is very small.
Bedaquiline should only be prescribed as part of an “effective” regimen and only after discussion within the MoH expert advisory group on management of XDR-TB.

The SA criteria and HML restrictions have been amended to refer to the MoH expert advisory group as follows (amendments in bold and strikethrough):

Special Authority for Subsidy

Initial application from any relevant practitioner.

Approvals valid for 6 months for applications meeting the following criteria: where:

Both All of the following:

  1. the patient has extensively drug-resistant tuberculosis (XDR-TB); and for whom
    1. treatment with bedaquiline has been recommended by a multidisciplinary clinical team with expertise in the treatment of tuberculosis, with input from infectious disease and respiratory specialists.
Note: A recommendation from the Ministry of Health’s Tuberculosis Clinical Network would be sufficient to meet criterion 2 of the Special Authority.Bedaquiline is indicated for a course of treatment of 24 weeks.
Bedaquiline should only be prescribed by infectious disease physicians and respiratory physicians PHARMAC consider that the requirement for a recommendation from a multidisciplinary clinical team with expertise in the treatment of tuberculosis, with input from infectious disease and respiratory specialists mitigates this concern.
Patients with XDR-TB are initiated on treatment in hospital; once cleared to leave hospital they continue to receive anti-TB medications via DOT, with most patients receiving blister packs for the Public/District Nurse to administer. This may be remote from the initiating hospital.Question whether there needs to be a process for hospitals to claim dispensing (like PCT) and distribute to community pharmacy to repack into DOT packs. Considers that Schedule listing needs to reflect this practice so that community pharmacies do not inadvertently procure a second pack.This in itself would cause issues in that the hospital would have claimed dispensing and the community pharmacy would need reimbursement for time/packing/dispensing in blister pack; and there would be issues related to capturing data. PHARMAC note that this issue appears to vary depending on the region that is treating the patient.Sirturo will be listed XPharm meaning distribution will be arranged by PHARMAC and that community pharmacies will not be able to dispense and claim for this pharmaceutical.PHARMAC will further investigate the best way to manage distribution and intends to resolve this prior to any listing on the Schedule.

Concerns that pharmacies would not want to stock this medicine noting:

  • It’s high cost.
  • small patient numbers who would be initiated in hospital so community pharmacy are unlikely to require a full pack.
  • the packs come in packs for 6 months’ worth of medicine (only 3 months medicine could be legally dispensed from pharmacy).
  • Wastage is a concern
Noted.PHARMAC will further investigate the best way to manage distribution and intend to resolve this prior to any listing on the Schedule.
Bedaquiline should only be dispensed from hospital pharmacies PHARMAC will further investigate the best way to manage distribution and intend to resolve this prior to any listing on the Schedule.
DOT can be provided by community pharmacies PHARMAC will further investigate the best way to manage distribution and intend to resolve this prior to any listing on the Schedule.

Siltuximab consultation feedback

Theme Comment
Supportive of proposal. Noted.
Noted the current accepted terminology is “HHV-8 idiopathic multicentric Castleman’s disease” and this should be accurately reflected in the proposal. Noted. PHARMAC has amended relevant documentation to reflect “HHV-8 idiopathic multicentric Castleman’s disease” or HHV-8 negative iMCD.
Patient estimates are generous, likely to be less patients but some likely to stay on treatment longer (Polynesian variant group).Noted some patients on compassionate supply of tocilizumab and these patients would switch to siltuximab. PHARMAC staff have incorporated feedback regarding patient group size, uptake and dosing into the financial analysis for this funding decision.
Considers the proposed Special Authority criteria should be amended.Noted the proposed criteria restrict access to patients with severe disease, consider this is appropriate but means criteria 2 and 3 do not make sense and should be deleted.

The Special Authority and HML restrictions have been amended as follows (amendments in bold and strikethrough):

Special Authority for subsidyInitial applicationonly from a haematologist or rheumatologist. Approvals valid for 6 months for applications meeting the following criteria:

All of the following:

1. Patient has severe HIV/HHV-8 negative idiopathic multicentric Castleman’s Disease; and

2. Treatment with at least 6 months of an adequate trial of corticosteroids has proven ineffective; and

3. Treatment with chemotherapy is clinically inappropriate; and

4. Siltuximab is to be administered at doses no greater than 11 mg/kg every 3 weeks.PHARMAC staff consider that the amended criteria better reflect the intended patient population and do not consider the changes widen access or change expected patient numbers.

Noted very high cost of siltuximab, and that a confidential rebate would apply. Considered this treatment would exceed current cost-benefit thresholds and noted high costs can be justified for small patient groups. PHARMAC staff note this proposal results from the Rare Disorders RFP and has been assessed following the process outlined in Schedule 2 of the RFP.
Considers there should be monitoring strategies to identify non-responders and those who may benefit from dose titration. Noted there may be additional cost offsets from hospitalisations avoided. PHARMAC note that C-reactive protein and haemoglobin are often used as surrogate markers of treatment efficacy for HHV-8 negative iMCD. We note that therapeutic drug monitoring and antibody testing for biologic agents may be available at some DHBs.
Supportive of proposals to list therapies that specifically target interleukin 6 (IL-6) for the treatment of HHV-8 negative iMCD and other non-infectious diseases where this cytokine pathway has been shown to be pathogenic. Provided summary of clinical evidence supporting siltuximab.Noted PHARMAC and those involved in assessing the evidence of efficacy for this proposal should be commended for speed of assessment and development of proposal. Noted growing recognition that biologic agents may lose efficacy in significant number of patients due to development of anti-drug antibodies. Local experience suggests at least 10% of patients on ant-TNF agents develop neutralising antibodies resulting in loss of drug efficacy.Requests PHARMAC remain open to funding alternative therapies which target the IL6/IL-6 receptor pathway in the future (i.e. tocilizumab). Noted.PHARMAC note tocilizumab for HHV-8 negative iMCD has been ranked by PHARMAC staff and remains an option for investment.We note this decision includes Sole Supply and Hospital Supply Status which applies to the siltuximab molecule, not the indication. This decision would therefore not prevent other alternative therapies for HHV-8 negative iMCD being considered for funding in the future.
Noted high cost of treatment for extremely rare conditions and this poses fiscal risk to community pharmacies in terms of stock holding. Concerns that the proposal was not patient centric to require patients to collect medicine from community pharmacy and take to hospital for infusion. Noted it would be better for it to be managed by hospital pharmacies and cheaper for DHBs. If out-patient infusion treatment with siltuximab devolves to general practice, considered this would be the appropriate time for siltuximab to be available through community pharmacy. PHARMAC consider siltuximab will be administered in the hospital out-patient setting. The listing in Section B will enable DHB hospitals to claim dispensings via the CPB if they choose to. We do not consider it likely that this agent would be administered in a community setting that is not administered by a DHB hospital at this time.

More information

Bedaquiline is approved in Europe and the United States. Janssen has submitted an application for registration to Medsafe, and it is currently under assessment (see http://www.medsafe.govt.nz(external link)).

Siltuximab is registered with Medsafe for the treatment of HIV/HHV-8 negative MCD (http://www.medsafe.govt.nz(external link))

If you have any questions about this decision, you can email us at enquiry@pharmac.govt.nz.