Listing of Pharmaceutical Benefits (NHL) - Schedule 4 part 1

Atypical haemolytic uraemic syndrome (aHUS)

Initial treatment - Initial (new patient) loading dose

Patient must have active and progressing thrombotic microangiopathy (TMA) caused by aHUS; AND

Patient must have ADAMTS-13 activity of greater than or equal to 10% on a blood sample taken prior to plasma exchange or infusion; or, if ADAMTS-13 activity was not collected prior to plasma exchange or infusion, patient must have platelet counts of greater than 30x10^9/L and a serum creatinine of greater than 150 mol/L; AND

Patient must have a confirmed negative STEC (Shiga toxin-producing E.Coli) result if the patient has had diarrhoea in the preceding 14 days; AND

Patient must have clinical features of active organ damage or impairment; AND

Patient must not receive more than 2 weeks of treatment under this restriction; AND

Must be treated by a prescriber who is either: (i) a haematologist, (ii) a nephrologist; or

Must be treated by a medical practitioner who has consulted at least one of the above mentioned specialist types, with agreement reached that the patient should be treated with this pharmaceutical benefit on this occasion; AND

Patient must be undergoing treatment with one C5 inhibitor therapy only at any given time.

This drug is not PBS-subsidised if it is prescribed to an in-patient in a public hospital setting.

Evidence of active and progressing TMA is defined by the following:

(1) A platelet count of less than 150x10^9/L; and evidence of at least two of the following:

(i) presence of schistocytes on blood film;

(ii) low or absent haptoglobin;

(iii) lactate dehydrogenase (LDH) above normal range; or

(2) In recipients of a kidney transplant for end-stage kidney disease due to aHUS, a kidney biopsy confirming TMA; and

(3) Evidence of at least one of the following clinical features of active TMA-related organ damage or impairment is defined as below:

(a) kidney impairment as demonstrated by one or more of the following:

(i) a decline in estimated Glomerular Filtration Rate (eGFR) of greater than 20% in a patient who has pre-existing kidney impairment;

(ii) a serum creatinine (sCr) of greater than the upper limit of normal (ULN) in a patient who has no history of pre-existing kidney impairment;

(iii) a sCr of greater than the age-appropriate ULN in paediatric patients;

(iv) a renal biopsy consistent with aHUS;

(b) onset of TMA-related neurological impairment;

(c) onset of TMA-related cardiac impairment;

(d) onset of TMA-related gastrointestinal impairment;

(e) onset of TMA-related pulmonary impairment.

Claims of non-renal TMA-related organ damage should be made at the point of application for initial PBS-subsidised ravulizumab (where possible), and should be supported by objective clinical measures.

The prescriber's cover letter should establish that the observed organ damage is directly linked to active and progressing TMA, particularly when indirect causes such as severe thrombocytopenia, hypertension and acute renal failure are present at the time of the initial organ impairment.

Serial haematological results (every 3 months while the patient is receiving treatment) must be provided with every subsequent application for treatment.

The authority application must be in writing and must include all of the following:

(1) Details of the proposed prescription(s);

(2) A completed authority application form relevant to the indication and treatment phase (the latest version is located on the website specified in the Administrative Advice);

(3) A detailed cover letter from the prescriber;

(4) A measurement of body weight at the time of application;

(5) The result of ADAMTS-13 activity on a blood sample taken prior to plasma exchange or infusion; the date and time that the sample for the ADAMTS-13 assay was collected, and the dates and times of any plasma exchanges or infusions that were undertaken in the 2 weeks prior to collection of the ADAMTS-13 assay;

(6) In the case that a sample for ADAMTS-13 assay was not collected prior to plasma exchange or infusion, measurement of ADAMTS-13 activity must be taken 7-10 days following the last plasma exchange or infusion. The ADAMTS-13 result must be submitted to Services Australia within 13 days of commencement of ravulizumab treatment in order for the patient to be considered as eligible for further PBS-subsidised C5 inhibitor treatment, under Initial balance of supply;

(7) A confirmed negative STEC result if the patient has had diarrhoea in the preceding 14 days;

(8) Evidence of active and progressing TMA, including pathology results where relevant. Evidence of the onset of TMA-related neurological, cardiac, gastrointestinal or pulmonary impairment requires a supporting statement with clinical evidence in patient records. All tests must have been performed within 4 weeks of application;

(9) For all patients, a recent measurement of eGFR, platelets and two of either LDH, haptoglobin or schistocytes of no more than 1 week old at the time of application.

Two authority prescription forms will be required to cover for the 26 weeks of initial therapy with ravulizumab, one for the loading dose and one for the 24 week balance which can be sought under the Balance of Supply.

Listing of Pharmaceutical Benefits (NHL) - Schedule 4 part 1

Atypical haemolytic uraemic syndrome (aHUS)

Switch from PBS-subsidised eculizumab (all phases) - loading dose

Patient must have previously received PBS-subsidised eculizumab under the 'Initial treatment' restriction for this condition; or

Patient must have previously received PBS-subsidised eculizumab under the 'Continuing treatment' restriction for this condition; or

Patient must have previously received PBS-subsidised eculizumab under the 'Extended continuing treatment' restriction for this condition; or

Patient must have previously received PBS-subsidised eculizumab under the 'Recommencement of treatment' restriction for this condition; or

Patient must have previously received PBS-subsidised eculizumab under the 'Continuing recommencement of treatment' restriction for this condition; AND

Patient must have/had ADAMTS-13 activity of greater than or equal to 10% on a blood sample; AND

Patient must not receive more than 2 weeks of treatment under this restriction; AND

Must be treated by a prescriber who is either: (i) a haematologist, (ii) a nephrologist; or

Must be treated by a medical practitioner who has consulted at least one of the above mentioned specialist types, with agreement reached that the patient should be treated with this pharmaceutical benefit on this occasion; AND

Patient must be undergoing treatment with one C5 inhibitor therapy only at any given time.

This drug is not PBS-subsidised if it is prescribed to an in-patient in a public hospital setting.

The application must indicate the most recent treatment phase that the patient is switching from.

For patients who are switching C5 inhibitors, the next application should be sought under the next relevant treatment phase.

Serial haematological results (every 3 months while the patient is receiving treatment) must be provided with every subsequent application for treatment.

The authority application must be in writing and must include all of the following:

(1) Details of the proposed prescription(s);

(2) A completed authority application form relevant to the indication and treatment phase (the latest version is located on the website specified in the Administrative Advice);

(3) A measurement of body weight at the time of application;

(4) Results of genetic testing, if not previously submitted.

Listing of Pharmaceutical Benefits (NHL) - Schedule 4 part 1

Atypical haemolytic uraemic syndrome (aHUS)

Recommencement of treatment

Patient must have demonstrated treatment response to previous treatment with a PBS-subsidised C5 inhibitor for this condition; AND

Patient must not have experienced treatment failure with ravulizumab for this condition in the most recent treatment phase; AND

Patient must have the following clinical conditions prior to recommencing C5 inhibitor treatment: (i) either significant haemolysis as measured by low/absent haptoglobin; or presence of schistocytes on the blood film; or lactate dehydrogenase (LDH) above normal; AND (ii) either platelet consumption as measured by either 25% decline from patient baseline or thrombocytopenia (platelet count <150 x 10^9/L); OR (iii) TMA-related organ impairment including on recent biopsy; AND

Must be treated by a prescriber who is either: (i) a haematologist, (ii) a nephrologist; or

Must be treated by a medical practitioner who has consulted at least one of the above mentioned specialist types, with agreement reached that the patient should be treated with this pharmaceutical benefit on this occasion; AND

Patient must be undergoing treatment with one C5 inhibitor therapy only at any given time.

This drug is not PBS-subsidised if it is prescribed to an in-patient in a public hospital setting.

A treatment response is defined as:

(1) Normalisation of haematology as demonstrated by at least 2 of the following: (i) platelet count, (ii) haptoglobin, (iii) lactate dehydrogenase (LDH); and

(2) One of the following:

a) an increase in eGFR of > 25% from baseline, where the baseline is the eGFR measurement immediately prior to commencing treatment with a C5 inhibitor; or

b) an eGFR within +/- 25% from baseline; or

c) an avoidance of dialysis-dependence but worsening of kidney function with a reduction in eGFR > 25% from baseline.

PBS-subsidised treatment with ravulizumab will not be permitted if a patient has experienced treatment failure with ravulizumab in the most recent treatment phase prior to the treatment phase where this application is sought.

A treatment failure is defined as a patient who is:

(1) Dialysis-dependent at the time of application and has failed to demonstrate significant resolution of extra-renal complications if originally presented; or

(2) On dialysis and has been on dialysis for 4 months of the previous 6 months while receiving a PBS-subsidised C5 inhibitor, and has failed to demonstrate significant resolution of extra-renal complications if originally presented.

The authority application must include the following measures of response to the prior course of treatment, including serial haematological results (every 3 months while the patient is receiving treatment).

The authority application must be in writing and must include all of the following:

(1) Details of the proposed prescription(s);

(2) A completed authority application form relevant to the indication and treatment phase (the latest version is located on the website specified in the Administrative Advice);

(3) A measurement of body weight at the time of application;

(4) Results of genetic testing, if not previously submitted;

(5) A family history of aHUS if applicable;

(6) A history of multiple episodes of aHUS following the treatment break, if applicable;

(7) A history of kidney transplant if applicable (especially if required due to aHUS);

(8) An inclusion of the individual consequences of recurrent disease;

(9) A supporting statement with clinical evidence of TMA-related organ damage including current (within one week of application) haematological results (platelet count, haptoglobin and LDH), eGFR level, and, if applicable, on recent biopsy;

(10) Evidence that the patient has had a treatment response to their previous treatment with a C5 inhibitor;

(11) Evidence that the patient has not experienced treatment failure, including a supporting statement with clinical evidence that the patient does not require dialysis, unless the indication for continuing ravulizumab is severe extra-renal complications that have significantly improved;

(12) If the indication for continuing ravulizumab is severe extra-renal complications, then a supporting statement with clinical evidence that any initial extra-renal complications of TMA have significantly improved is required.

Two authority prescription forms will be required to cover for the 26 weeks of recommencement therapy with ravulizumab, one for the loading dose and one for the 24 week balance which can be sought under the Balance of Supply.