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

Atypical haemolytic uraemic syndrome (aHUS)

Continuing treatment

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

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

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

Patient must have demonstrated on-going treatment response with PBS-subsidised eculizumab for this condition; AND

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

Patient must not receive more than 80 weeks of eculizumab 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 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.

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 eculizumab will not be permitted if a patient has experienced treatment failure with eculizumab 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) A completed authority prescription form(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 eculizumab is severe extra-renal complications that have significantly improved;

(10) If the indication for continuing eculizumab 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 eculizumab.

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

Atypical haemolytic uraemic syndrome (aHUS)

Extended Continuing treatment

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

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

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

Patient must have demonstrated on-going treatment response with PBS-subsidised eculizumab for this condition; AND

Patient must not have experienced treatment failure with eculizumab 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 eculizumab; AND

Patient must not receive more than 24 weeks of treatment 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.

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 eculizumab will not be permitted if a patient has experienced treatment failure with eculizumab 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) A completed authority prescription form(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 eculizumab 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 eculizumab is severe extra-renal complications that have significantly improved;

(12) If the indication for continuing eculizumab 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 eculizumab.

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 PBS-subsidised eculizumab for this condition; or

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

Patient must not have experienced treatment failure with eculizumab 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

Patient must not receive more than 24 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.

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 eculizumab will not be permitted if a patient has experienced treatment failure with eculizumab 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) A completed authority prescription form(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 eculizumab;

(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 eculizumab is severe extra-renal complications that have significantly improved;

(12) If the indication for continuing eculizumab 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.

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

Atypical haemolytic uraemic syndrome (aHUS)

Continuing recommencement of treatment

Patient must have received PBS-subsidised eculizumab under the recommencement of treatment phase for this condition; or

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

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

Patient must not receive more than 24 weeks of treatment with eculizumab 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.

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 eculizumab will not be permitted if a patient has experienced treatment failure with eculizumab 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) A completed authority prescription form(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 eculizumab 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 eculizumab is severe extra-renal complications that have significantly improved;

(11) If the indication for continuing eculizumab 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 eculizumab.

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

Atypical haemolytic uraemic syndrome (aHUS)

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

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

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

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

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

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

Patient must have previously received PBS-subsidised ravulizumab under the 'Grandfather (transitioning from non-PBS to PBS-subsidised 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 24 weeks of C5 inhibitor supply for this current treatment phase 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.

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) A completed authority prescription form(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.