Poly-l-lactic acid, powder for injection, 150 mg, Sculptra®, March 2009
Public summary document for Poly-l-lactic acid, powder for injection, 150 mg, Sculptra®, March 2009
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Public Summary Document
Product:Poly-l-lactic acid, powder for injection,
150 mg, Sculptra®
Sponsor:Sanofi-Aventis Australia Pty Ltd
Date of PBAC Consideration: March 2009
1. Purpose of Application
The submission sought an Authority Required listing for the
treatment of facial lipoatrophy caused by antiretroviral therapy in
HIV positive patients.
2. Background
An application to list this product was rejected at the November
2008 PBAC meeting. The Committee agreed that it was appropriate to
consider this product for inclusion on the PBS, given that it had a
biological action additional to its mechanical effect. The PBAC
also acknowledged the substantial impact that facial lipoatrophy
had on the quality of life of HIV patients and recognised the
clinical need for treatment options for patients experiencing this
unfortunate side effect of anti-retroviral treatment.
The PBAC concluded that there were a number of assumptions in the
economic model, which resulted in uncertain cost effectiveness, and
the submission was rejected on this basis. The Committee indicated
its willingness to work with the sponsor towards reducing this
uncertainty sufficiently to allow a listing recommendation.
3. Registration Status
Sculptra was originally registered on the ARTG in 2002, it was then
reregistered by TGA in 2008 as part of the new medical device
regulations. The functional description of the device on the
register was for ‘soft tissue augmentation via intradermal or
subcutaneous injection of poly-l-lactic acid. The product requires
hydration and suspension prior to use. It provides a physical
filling effect.
4. Listing Requested and PBAC’s View
Authority Required
Initial PBS-subsidised treatment of facial lipoatrophy caused by
therapy for HIV infection.
Authority Required
Maintenance PBS-subsidised treatment of facial lipoatrophy caused
by therapy for HIV infection.
For PBAC’s view see Recommendation and
Reasons.
5. Clinical Place for the Proposed Therapy
Facial lipoatrophy is one of the adverse effects of highly active
antiretroviral therapy that is of most concern to patients with
HIV. Treatment with poly-l-lactic acid reverses the visible effects
of facial lipoatrophy and improves the quality of life for HIV
patients.
6. Comparator
The submission nominated placebo as the main comparator.
7. Clinical Trials
The submission presented no new clinical data.
See November 2008 Public Summary Document for this
information.
8. Results of Trials
The main clinical results, as presented to PBAC in November 2008 and detailed in the Public Summary document are reproduced below.
The results of change in dermal thickness (in mm) in the randomised trials are shown in the following table
| Poly-L-lactic acid | No treatment | Mean difference (95% CI) | |
| Carey 2007 0–24 weeks | N = 50 mean (95% CI) | N = 50 mean (95% CI) | |
| Nasal septum | 1.3 (0.7, 1.8) | 0.3 (-0.1, 0.6) | 1.0 (0.3, 1.6) |
| Maxilla | 2.3 (1.7, 2.8) | 0.1 (-0.3, 0.4) | 2.2 (1.6, 2.9) |
| Moyle 2004 0–12 weeks | N = 15 mean (SD) | N = 8 mean (SD) | |
| L nasolabial fold | 3.9 (2.1) | 0.1 (0.6) | 3.8 (2.5, 5.1) |
| R nasolabial fold | 4.3 (2.9) | 0.2 (0.7) | 4.1 (2.4, 5.8) |
| L cheek | 4.1 (2.8) | 0.4 (0.4) | 3.7 (2.1, 5.3) |
| R cheek | 3.9 (2.4) | 0.3 (0.4) | 3.6 (2.2, 5.0) |
The results of mean change in quality of life measures, 0-24 weeks (Carey et al, a randomized, multicenter, open-label study of poly-L-lactic acid for HIV-1 facial lipoatrophy, Journal of Acquired Immune Deficiency Syndromes 2007;46(5): 581-589) is shown in the following table
| Carey 2007 | Poly-L-lactic acid N = 50 | No treatment N = 50 | Mean difference | p-value |
| SF-36 General Health Questionnaire sub-scales | ||||
| Social Functioning | 2.0 | – 6.8 | 8.8 | 0.031 |
| Mental Health Component | 3.5 | – 3.4 | 6.9 | 0.047 |
| Multidimensional Body-Self Relations Questionnaire – Appearance Scales* | ||||
| Appearance evaluation | 0.15 | -0.15 | 0.30 | 0.010 |
| Body areas satisfaction | 0.19 | -0.11 | 0.30 | 0.0004 |
* a higher score indicates that the patient is positive and
satisfied with their appearance
Note: standard deviations were not provided in the source article,
so 95% confidence intervals for the mean differences could not be
calculated.
The results of mean change 0-12 weeks in the Hospital Anxiety and
Depression Scale Moyle 2004 (Chelsea and Westminster Study), a
randomized open-label study of immediate versus delayed polylactic
acid injections for the cosmetic management of facial lipoatrophy
in persons with HIV infection, HIV Medicine 2004;5(2): 82-7) are
shown in the following table:
| Moyle 2004 | Poly-L-lactic acid | No treatment | Mean difference | ||||
| n | Baseline: mean (SD) | Change: mean (SD) | n | Baseline: mean (SD) | Change: mean (SD) | ||
| 12 week follow up | |||||||
| Anxiety | 15 | 8.7 (4.7) | -2.7 (4.6) | 14 | 9.9 (5.9) | 0.3 (4.0) | 3.0 (-6.3, 0.3) |
| Depression | 14 | 6.0 (4.3) | -1.9 (3.4) | 14 | 7.2 (5.3) | -0.2 (3.9) | -1.7 (-4.5, 1.1) |
9.Clinical Claim
The submission described poly-l-lactic acid (PLLA) as superior in
terms of comparative effectiveness and equivalent in terms of
comparative safety over no treatment.
The PBAC had previously noted that poly-l-lactic acid was generally
well tolerated in trials; the main adverse effect being the
occurrence of subcutaneous papules or nodules
10. Economic Analysis
The re-submission sought to address key issues that were identified
by the PBAC in the previous submission considered at the November
2008 PBAC meeting. The PBAC’s intent was that the base case
should be re-specified to include more conservative estimates to
the variables listed below. If no changes were to be made, a
justification should be presented by the sponsor.
The issues identified were in regards to quality of life benefit,
cost-effectiveness, consideration of non-responders and MBS cost
implications. The resubmission presented sensitivity analyses
associated with these issues.
The submission conducted a number of multivariate sensitivity
analyses, with a base case of between $15,000 - $45,000/QALY.
The model was very sensitive to changes in the reduction of the
size of the improvements with each re-treatment.
11. Estimated PBS Usage and Financial Implications
The submission estimated between 10,000 – 50,000 vials would
be used at an estimated cost of poly-l-lactic acid to the PBS of
< $10 million in Year 3 of listing.
12. Recommendation and Reasons
The PBAC recommended the listing of poly-L-lactic acid on the PBS
for the treatment of severe facial lipoatrophy caused by therapy
for HIV infection on the basis of clinical need and high and
uncertain but acceptable cost effectiveness compared with
placebo.
The PBAC noted the social and psychological impact that results
from facial lipoatrophy which was highlighted in the submission and
in the consumer comments and also the impact that facial
lipoatrophy has on the quality of life of people with this
condition as a result of their treatment for HIV. The PBAC agreed
that there was a clinical need for this product.
The PBAC noted that the issues identified in relation to the
previous submission considered in November 2008 had been addressed.
However, the Committee did not accept the sponsor’s argument
for not presenting a utility analysis using the SF-36 General
Health Questionnaire Sub-Scale data from the Carey 2007 trial, and
considered that presentation of SF-6D weights from the Carey trial
data would have been informative as a sensitivity analysis.
Multivariate sensitivity analyses conducted during the evaluation
indicated that the incremental cost effectiveness ratio could be in
the $45,000 - $75,000 range per extra Quality Adjusted Life Year
(QALY) gained from a base case of between $15,000 - $45,000/QALY.
The PBAC noted that the model was sensitive to the assumptions in
relation to the size of the quality of life gains and to changes in
the reduction of the size of the improvements with each
re-treatment. The PBAC considered that economic uncertainty
remained because some assumptions in the model were not fully
justified, for example the assumption that all the disutility from
lipodystrophy is associated with facial lipoatrophy. However the
PBAC acknowledged that the trial results demonstrated significant
improvements in social function and mental health.
The PBAC considered, as recommended following its November 2008
PBAC meeting, that the sponsor should continue to manage the
accreditation program, associated administrative records and the
distribution of drug to company approved prescribers to ensure
competency in its injection into patients.
Recommendation
POLY-L-LACTIC ACID, powder for injection, 150 mg
Restriction:
Authority Required:
Initial PBS-subsidised treatment, for facial administration only,
of severe facial lipoatrophy caused by therapy for HIV
infection.
Max. Qty: 2
Repeats: 4
Authority Required:
Maintenance PBS-subsidised treatment, for facial administration
only, of severe facial lipoatrophy caused by therapy for HIV
infection.
Max. Qty: 2
Repeats: 0
NOTE: Maintenance treatment is limited to one re-treatment (2
vials) every 2 years.
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
Sanofi-aventis appreciates the opportunity to work with the PBAC,
to address the unmet need for poly-L-lactic acid in HIV patients
living with facial lipoatrophy.
