Efalizumab, injection set containing 4 vials powder for injection 125 mg and 4 pre-filled syringes solvent 1.3 mL, Raptiva®, July 2005
Public Summary Document for Efalizumab, injection set containing 4 vials powder for injection 125 mg and 4 pre-filled syringes solvent 1.3 mL, Raptiva®, July 2005.
Page last updated: 24 October 2005
Public Summary Document
Product: Efalizumab, injection set containing 4 vials powder for injection 125 mg and 4 pre-filled
syringes solvent 1.3 mL, Raptiva®
Sponsor: Serono Australia Pty Ltd
Date of PBAC Consideration: July 2005
1. Purpose of Application
This application sought listing on the Pharmaceutical Benefits Scheme (PBS) as a section 100 item (Highly Specialised Drug) for adults with severe chronic plaque psoriasis who met certain criteria. (Highly Specialised Drugs (HSDs) are medicines for the treatment of chronic conditions, which, because of their clinical use or other special features, are restricted to prescribing through public and private hospitals which have appropriate specialist facilities).
2. Background
This is the second application to list efalizumab on the PBS. This application was
designed to address issues arising from the rejection of the first submission and
from the stakeholder meeting which was held in December 2004. The second application
is the subject of this Public Summary Document (PSD).
The Pharmaceutical Benefits Advisory Committee (PBAC), at its meeting in November
2004, rejected the first application to list efalizumab as authority required for
adults with severe plaque psoriasis who have failed to achieve an adequate response
to, or are contraindicated to at least two systemic therapies.
The PBAC considered that there was good evidence of effectiveness of the drug in patients
with severe psoriasis in terms of the reduction in Psoriasis Area and Severity Index
(PASI) score, for up to 12 months of treatment, but was concerned about the long term
safety of the drug, beyond the 12-month time horizon.
Despite good evidence of clinical effectiveness, the base case modelled incremental
cost per extra discounted QALY gained was considered unacceptably high. The PBAC therefore
rejected the submission because of unacceptable cost-effectiveness.
This resulted in a stakeholders meeting to discuss the place of new biological agents
in the treatment of psoriasis that was held on 15 December 2004.
3. Registration Status
Efalizumab was registered for marketing on 6 October 2004 for the “treatment of adult patients with moderate to severe chronic plaque psoriasis, who are candidates for phototherapy or systemic therapy. Safety and efficacy beyond 12 months have not been established.”
4. Listing Requested and PBAC’s View
The submission requested an authority required listing (private and public hospitals)
as a section 100 item (Highly Specialised Drug). Under the requested listing, initial
treatment would have been limited to patients with severe chronic plaque psoriasis
who met certain criteria including a failure to achieve an adequate response to specified
psoriasis therapies and a PASI score > 15. Eligibility for continuing PBS-subsidised
treatment would have been contingent on the achievement and maintenance of a reduction
of at least 50% in the PASI score.
Although not a reason for rejection, the PBAC considered that there were some outstanding
issues with the requested restriction in terms of rigorously identifying both eligible
patients and then adequate responders. In particular, the intention would be for the
baseline PASI to be in the presence of prior therapy in order to demonstrate failure
to achieve an adequate response with that treatment, an intention similar to that
already in place to demonstrate failure to achieve an adequate response to prior disease
modifying antirheumatic drugs (DMARDs) in recent listings for rheumatoid arthritis.
The PBAC also noted advice from the Highly Specialised Drugs Working Party that it
did not consider that efalizumab should be listed as a section 100 drug. Most dermatologists
work in private practice and thus listing under section 100 would be likely to disadvantage
a large number of patients. Although cyclosporin must be initiated in outpatients’
clinics, this is related to its toxicity rather than the need to treat psoriasis in
the setting of outpatients’ clinics.
The PBAC also noted that the National Institute for Clinical Excellence (NICE) in
the UK has released a preliminary consultation report, that considered an alternative
PASI threshold for severe psoriasis, and PASI improvement for determining whether
patients can continue therapy.
5. Clinical Place for the Proposed Therapy
Psoriasis is a chronic, incurable inflammatory disorder that, although not life-threatening, can severely impact on a patient’s quality of life. Current psoriasis therapies reduce the symptoms for this chronic disease. Efalizumab is proposed as a treatment for patients with severe refractory psoriasis who have little or no alternative therapies.
6. Comparator
The submission nominated placebo as the comparator in view of the refractory nature of the proposed treatment population. The choice of comparator was considered appropriate by the PBAC.
7. Clinical Trials
The key clinical trial evidence reflects the specific population of severe psoriasis
sufferers that would be eligible for subsidised treatment. The key clinical trial
evidence came from a single double blind placebo controlled study (24011) of efalizumab
1mg/kg/week in “high needs” patients who were unresponsive, intolerant or contraindicated
to ≥2 systemic therapies and had a baseline PASI >15. Longer term, 24 month, supportive
evidence came from study 2390 and its open label extension 2391.
At the time of submission, the two latter studies had been published as follows:
|
Trial/first author |
Protocol title |
Publication citation |
|---|---|---|
| 2390/ 1. Gordon 2. Papp Ricardo |
Efalizumab for patients with moderate to severe plaque psoriasis. | 1. JAMA 2003; 29: 3073 – 3080 2. Drugs of Today 40 (?) 00- 00 3. Cutis 2004; 74 (Sept): 193 – 200 |
| 2391/ Menter |
Efficacy and safety observed during 24 weeks of efalizumab therapy in patients with moderate to severe psoriasis. | Arch Dermatol 2005; 141: 31-38 |
Results from Study 24011 were presented at the European Association of Dermatology and Venereology (EADV) Conference in Budapest in April 2004.
8. Results of Trials
In trial 24011 there was a statistically significant difference in the proportion
of patients achieving at least a 50% reduction in their PASI score in the efalizumab
group (approximately 50%) compared to the placebo group (approximately 13%).
In trial 24011, infection rates for efalizumab (approximately 20%) were almost twice
those for placebo. Serious adverse events were similar in both groups occurring in
about 5% of both efalizumab and placebo treated patients.
New longer-term toxicity data were presented in the submission based on a randomised
trial comparing 27 months of treatment with efalizumab and topical ointment with efalizumab
alone. In each 12 week treatment cycle, infections occurred on average in approximately
15% of patients, serious adverse events in approximately 3% of patients and skin carcinomas
in 0.7% of patients.
9. Clinical Claim
The submission claimed that efalizumab is significantly more effective than placebo,
but is more toxic, which reflects one of the categories for clinical claims within
the PBAC guidelines.
As previously, the PBAC agreed that efalizumab is an effective drug in terms of a
PASI 50% improvement. Thus the PBAC accepted that efalizumab is significantly more
effective than placebo, but is more toxic.
10. Economic Analysis
An updated (since the previous submission) preliminary economic evaluation was presented.
An updated modelled economic evaluation was presented. The model differed from the previous submission by adjusting a number of key parameters.
The base case modelled incremental discounted cost per extra discounted quality adjusted life year (QALY) fell in the range $45,000 - $75,000.
For PBAC’s view on the economic analysis, see Recommendation and Reasons.
11. Estimated PBS Usage and Financial Implications
The submission estimated that the likely number of patients to be eligible for treatment with efalizumab per year to be <10,000 by Year 4 with a financial cost per year to the PBS of up to $30 - $60 million per year by Year 4 of listing.
12. Recommendation and Reasons
As previously, the PBAC agreed that efalizumab is an effective drug in terms of a
PASI 50% improvement. Thus the PBAC accepted that efalizumab is significantly more
effective than placebo, but is more toxic. The PBAC also noted that by adjusting some
of the parameters modelled in the submission there was a major improvement in the
cost per QALY gained.
The PBAC noted some concerns with the derivation of the utility values used in the
economic model. Despite these concerns, the PBAC considered that the incremental cost
per extra QALY gained was reasonably robust, although it would increase if a recommendation
to list under section 85 of the PBS (i.e. as an authority required item) were made
instead of section 100 prescribing. Although efalizumab is effective and there is
a demonstrated need in this patient group, the PBAC considered that the base case
cost-effectiveness ratio was high.
The PBAC therefore rejected the submission because of unacceptable cost-effectiveness.
13. Context for Decision
The PBAC helps decide whether and, if so, how medicines should be subsidised in Australia. It considers submissions in this context. A PBAC decision not to recommend listing or not to recommend changing a listing does not represent a final PBAC view about the merits of the medicine. A company can resubmit to the PBAC or seek independent review of the PBAC decision.
14. Sponsor’s Comment
Serono has consistently demonstrated its willingness to work constructively with relevant stakeholders to ensure that Raptiva is made available, under reimbursement, as soon as possible. Serono seeks a recommendation for the listing of Raptiva on the PBS for the population of patients suffering severe psoriasis who are uncontrolled by current systemic therapy.
