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

Atypical haemolytic uraemic syndrome (aHUS)

Balance of Supply - maintenance doses

Patient must have received PBS-subsidised loading dose of ravulizumab for this condition for this current treatment phase; AND

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

Patient must have received insufficient therapy to complete the maximum allowable treatment under their specified treatment phase; AND

The treatment must provide no more than the balance of up to 24 weeks treatment available under the relevant treatment phase; 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.

ADAMTS-13 activity result must have been submitted to Services Australia. In the case that a sample for ADAMTS-13 activity taken prior to plasma exchange or infusion was not available at the time of application for Initial treatment, ADAMTS-13 activity must have been measured 7-10 days following the last plasma exchange or infusion and must have been submitted to Services Australia within 13 days of commencement of ravulizumab. The date and time that the sample for the ADAMTS-13 assay was collected, and the dates and times of the last, if any, plasma exchange or infusion that was undertaken in the 2 weeks prior to collection of the ADAMTS-13 assay must also have been provided to Services Australia.

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

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

Atypical haemolytic uraemic syndrome (aHUS)

Continuing treatment

Patient must have received PBS-subsidised ravulizumab under the initial treatment phase for this condition; or

Patient must have received PBS-subsidised ravulizumab under the switch from eculizumab in the continuing treatment phase for this condition; or

Patient must have received PBS-subsidised ravulizumab under the grandfather restriction for this condition; AND

Patient must have demonstrated ongoing treatment response with PBS-subsidised ravulizumab 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 not receive more than 72 weeks of ravulizumab treatment in total under this restriction; or

Patient must not receive more than 104 weeks supply of a C5 inhibitor under the initial and continuing treatment restrictions if they had switched C5 inhibitors during the course of initial and continuing treatment; AND

Patient must not receive more than 24 weeks of treatment with ravulizumab per continuing treatment course authorised 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.

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 kidney transplant if applicable (especially if required due to aHUS);

(7) An inclusion of the individual consequences of recurrent disease, if applicable;

(8) Evidence that the patient has had a treatment response including haematological results of no more than 1 week old at the time of application (platelet count, haptoglobin and LDH); and an eGFR level of no more than 1 week old at the time of application;

(9) 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;

(10) 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.

This assessment must be submitted no later than 4 weeks from the cessation of the prior treatment. Where a response assessment is not undertaken and submitted within these timeframes, the patient will be deemed to have failed to respond to treatment with ravulizumab.

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

Atypical haemolytic uraemic syndrome (aHUS)

Extended continuing treatment

Patient must have received PBS-subsidised ravulizumab under the continuing treatment phase for this condition; or

Patient must have received PBS-subsidised ravulizumab under the switch from eculizumab in the continuing treatment phase for this condition; or

Patient must have received PBS-subsidised ravulizumab under the switch from eculizumab in the extended continuing treatment phase for this condition; AND

Patient must have demonstrated ongoing treatment response with PBS-subsidised ravulizumab 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 a TMA-related cardiomyopathy as evidenced by left ventricular ejection fraction < 40% on current objective measurement; or

Patient must have severe TMA-related neurological impairment; or

Patient must have severe TMA-related gastrointestinal impairment; or

Patient must have severe TMA-related pulmonary impairment on current objective measurement; or

Patient must have grade 4 or 5 chronic kidney disease (eGFR of less than 30 mL/min); or

Patient must have a high risk of aHUS recurrence in the short term in the absence of continued treatment with ravulizumab; AND

Patient must not receive more than 24 weeks of treatment with ravulizumab per continuing treatment course authorised 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.

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 before commencing ravulizumab treatment, 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 severe TMA-related cardiomyopathy (including current LVEF result), neurological impairment, gastrointestinal impairment or pulmonary impairment;

(10) Evidence that the patient has had a treatment response including haematological results of no more than 4 weeks old at the time of application (platelet count, haptoglobin and LDH); and an eGFR level of no more than 4 weeks old at the time of application;

(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.

This assessment must be submitted no later than 4 weeks from the cessation of the prior treatment. Where a response assessment is not undertaken and submitted within these timeframes, the patient will be deemed to have failed to respond to treatment with ravulizumab.

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

Atypical haemolytic uraemic syndrome (aHUS)

Continuing recommencement of treatment

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

Patient must have received PBS-subsidised ravulizumab under the switch from eculizumab 'Recommencement treatment' restriction for this condition; or

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

Patient must have demonstrated ongoing treatment response to 'Recommencement of treatment' with a 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 not receive more than 24 weeks of treatment with ravulizumab per continuing treatment course authorised 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.

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 before recommencing ravulizumab treatment, 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, if applicable;

(9) Evidence that the patient has had a treatment response including haematological results of no more than 1 week old at the time of application (platelet count, haptoglobin and LDH); and an eGFR level of no more than 1 week old at the time of application;

(10) 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;

(11) 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.

This assessment must be submitted no later than 4 weeks from the cessation of the prior treatment. Where a response assessment is not undertaken and submitted within these timeframes, the patient will be deemed to have failed to respond to treatment with ravulizumab.

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

Atypical haemolytic uraemic syndrome (aHUS)

Transitioning from non-PBS to PBS-subsidised treatment - Grandfather arrangements

Patient must have previously received non-PBS-subsidised therapy with this drug for this condition; AND

Patient must have met all other PBS eligibility criteria that a non-'Grandfather' patient would ordinarily be required to meet, meaning that at the time non-PBS supply of a C5 inhibitor treatment was commenced, the patient: (i) had active and progressing thrombotic microangiopathy (TMA) caused by aHUS; (ii) had ADAMTS-13 activity of greater than or equal to 10% on a blood sample not confounded by any plasma exchange or infusion; (iii) had a confirmed negative STEC (Shiga toxin-producing E.Coli) result if the patient has had diarrhoea in the preceding 14 days of commencing C5 inhibitor treatment; (iv) had clinical features of active organ damage or impairment; AND

Patient must have demonstrated ongoing treatment response with ravulizumab for this condition if received at least 26 weeks of initial non-PBS-subsidised therapy; AND

Patient must not have experienced treatment failure with ravulizumab for this condition if they have received at least 26 weeks of initial non-PBS-subsidised therapy; 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 two weeks prior to collection of the ADAMTS-13 assay;

(6) A confirmed negative STEC result if the patient has had diarrhoea in the preceding 14 days of initiating treatment with non-PBS-subsidised C5 inhibitor treatment;

(7) 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 commencement of non-PBS-subsidised C5 inhibitor treatment;

(8) For patients who have received at least 26 weeks of ravulizumab treatment, 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.