Coal Tar Prepared , emulsion, 10 mg per g (1%), Exorex® , July 2005
Public Summary Document forCoal Tar Prepared , emulsion, 10 mg per g (1%), Exorex® July 2005
Page last updated: 24 October 2005
Public Summary Document
Product: Coal Tar Prepared , emulsion, 10 mg per g (1%), Exorex®
Sponsor: EpiPharm Pty Limited
Date of PBAC Consideration: July 2005
1. Purpose of Application
This application sought listing on the Pharmaceutical Benefits Scheme (PBS) as an unrestricted benefit of a 1% coal tar preparation (Exorex) for the treatment of chronic psoriasis.
2. Background
This is the second application for PBS listing of Exorex.
The Pharmaceutical Benefits Advisory Committee (PBAC) rejected a submission for Exorex at its November 2004 meeting.
3. Registration Status
Exorex penetrating emulsion psoriasis medication is registered by the Therapeutic Goods Administration for the relief of symptoms of psoriasis of the skin and scalp.
4. Listing Requested and PBAC’s View
The submission requested listing as an unrestricted benefit.
The PBAC agreed this was appropriate.
5. Clinical Place for the Proposed Therapy
The submission claimed that patients have a preference for ready-prepared coal tar products compared with extemporaneous coal tar products (those prepared by a pharmacist), due to cosmetic properties such as smell, staining of clothing or skin and ease of application.
In addition the submission claimed that pharmacists have indicated that the major disadvantages of supplying extemporaneous coal tar preparations are time, mess and cost.
6. Comparator
The submission nominated extemporaneous coal tar preparations as the comparator.
This was accepted as appropriate by PBAC.
7. Clinical Trials
The submission presented the results of two randomised clinical trials, both of which have been published as follows:
|
Trial/first author |
Protocol title |
Publication citation |
|---|---|---|
| Goodfield M, Kownacki S, Berth-Jones J. | Double-blind, randomised, multicentre, parallel group study comparing a 1% coal tar preparation** (Exorex® ) with a 5% coal tar preparation** (Alphosyl® ) in chronic plaque psoriasis. | J Dermatol Treatment 2004; 15:14–22. |
| van der Valk PGM | A new coal tarextract (Exorex ® lotion) in the treatment of psoriasis and atopic dermatitis; experiences in the Netherlands. (Exorex® vsextemporaneous preparation containing coal tar (liquor carbonis detergens 10% in lannette wax cream, white petrolatum ana) | Available at: http://www.exorex.de/doc/clinical-studie.pdf (Last accessed: 3 March 2005) |
**Both Exorex® and Alphosyl® contain 5% alcoholic extract of coal tar. The final concentration of coal tar in Exorex® and Alphosyl® is approximately 1%. Alphosyl® also contains 0.5% hydrocortisone and 2% allantoin.
A third study, Smith CH et al(a double-blind, randomised, controlled clinical trial to assess the efficacy of a new coal tar preparation (Exorex® ) in the treatment of chronic, plaque-type psoriasis (n = 20), Clin Exp Dermatol 2000; 25:580-3), was excluded from the re-submission by the sponsor. The exclusion of this small trial was accepted by the PBAC on the basis that Exorex was compared with another coal tar product whose vehicle contained a polyunsaturated fatty acid in its formulation.This compound may have influenced outcomes in ways similar to that of the Exorex formulation, which also contained un-esterified free fatty acids.
The van der Valk et al trial involved the most appropriate comparator, but little information was provided.
The Goodfield et al trial for which details were available did not use the appropriate comparator and compared Exorex® with another commercial product of coal tar which contains 0.5% hydrocortisone and 2% allantoin (Alphosyl® ). The primary efficacy endpoint for this trial was the change in psoriasis severity from baseline, assessed using the Total Sign Score (TSS), also known as Psoriasis Severity Index (PSI), a commonly accepted clinical measure of psoriasis severity.
8. Results of Trials
The results of the Goodfield et al trial are reported in the table below.
Mean change in TSS scores from baseline and until the end of 12-week treatment in Goodfield et al (2004)
|
Psoriasis severity outcomes |
Number of patients 1 |
Mean change in TSS scores from baseline |
Treatment difference (95% CI) |
p-value 2 |
||
|---|---|---|---|---|---|---|
|
Exorex® (N) |
Control (N) |
Exorex® Mean % (SD) |
Control Mean % (SD) |
|||
| Mean percentage change in TSS score Goodfield et al (2004) |
158 (ITT: 167) |
166 (ITT: 171) |
- 39.8% (48.39) |
- 29.3% (49.73) |
- 10.6 ( - 20.6, - 0.5) |
0.04 |
Statistically significant differences are presented in bolded typeface.
CI, confidence interval; N, number of patients in each treatment arm who received ?1 application of treatment; SD, standard deviation (calculated for the original submission using Review Manager 4.2)
1 Patients who had taken ?1 dose of medication. 2 Statis tical analysis as reported in Goodfield et al (2004)
The Goodfield et al trial showed a greater improvement in TSS scores (approximately 40% improvement) as compared toAlphosyl® (approximately 30% improvement).
The results of the trial reported by van der Valk et al (1998) are summarised below. This trial used the Psoriasis Area and Severity Index (PASI) as a measure of improvement. For comparison, the PASI outcomes in Goodfield et al (2004) trial are also presented however, as noted by the PBAC in November 2004, these are of a limited value because only selected plaques were treated in patients enrolled in this trial.
Mean percentage change in PASI scores from baseline and until the end of 12-week treatment in Goodfield (2004), and the end of each 3-week interval of the cross-over trial by van der Valk (1998)
|
Psoriasis severity outcomes |
Number of patients 1 |
Mean change in PASI scores |
Treatment difference (95% CI) |
p-value 2 |
||
|---|---|---|---|---|---|---|
|
Exorex®
(N)
|
Coal tar
(N)
|
Exorex ®
Mean % (SD)
|
Control
Mean % (SD
|
|||
| Mean percen tage change in PASI score Goodfield (2004) |
158 (ITT: 167) |
166 (ITT: 171) |
- 33.4% (58.07) |
- 21.7% (59.91) |
- 11.7 ( -23.8, 0.4) |
0.06 |
|
Mean (95% CI)
|
Mean (95% CI)
|
|||||
| Mean percentage change in PASI score van der Valk (1998) |
12 |
12 |
-33% |
- 7.5% |
- 25.5% |
NR |
CI, confidence interval; N, number of patients in each treatment arm who received ?1 application of treatment; NR, not reported; SD, standard deviation (calculated for the original submission using Review Manager 4.2)
1 Patients who had taken ?1 dose of medication. 2 Statistical analysis as reported in Goodfield et al (2004).
The van der Valk trial showed a 33% improvement in PASI scores for Exorex compared to a 7.5% improvement for the comparator.
No new toxicity data were presented in the re-submission.
9. Clinical Claim
The submission claimed that Exorex had significant clinical advantages over other coal tar preparations, had superior effectiveness to other coal tar preparations, and similar toxicity.
10. Economic Analysis
A preliminary economic evaluation was performed comparing Exorex with extemporaneous coal tar preparations based on the pivotal clinical trial.
The submission also provided a modelled economic evaluation in which Exorex was dominant (more effective and less costly) in the base case modelled incremental cost per extra month not on systemic therapies.
11. Estimated PBS Usage and Financial Implications
The likely number of prescriptions dispensed per year was estimated by the submission to be in the range 10,000 – 50,000 in Year 3, with the net financial costs to the PBS of less than < $10 million per year by Year 3.
The PBAC considered that this estimate is sensitive to assumptions of the extent of market expansion should Exorex® be listed on the PBS.
12. Recommendation and Reasons
The PBAC recommended listing on the basis of acceptable cost-effectiveness compared with extemporaneous preparations containing coal tar.
While recognising the limitations of the evidence presented, the PBAC accepted that the Goodfield et al (2004) trial demonstrated advantages in efficacy for Exorex compared with another commercial coal tar product, Alphosyl® . The 10.6% increment in percentage change in TSS from baseline over 12 weeks favouring Exorex was accepted by the PBAC as clinically relevant.
Recommendation:
List
| Restriction: | Unrestricted |
| Maximum Quantity:
Repeats: |
1
2 |
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
EpiPharm Pty Ltd were pleased that the PBAC recognised the clinical need for listing a pre-prepared, bottled coal tar treatment in Exorex.
