Talimogene Laherparepvec
Treatment of unresectable stage III or stage IV malignant melanoma without visceral metastases (stage IIIb/c and stage IVM1a).
Decision on record
- Meeting Jul 2016 Not recommended Melanoma
From the public summary
7.1 The PBAC rejected the listing of T-VEC on the basis of highly uncertain magnitude of clinical benefit, and thus highly uncertain cost effectiveness compared to its nominated comparators (pembrolizumab, nivolumab and ipilimumab).PSD · Jul 2016
7.2 The PBAC acknowledged that there may be some short-term unmet clinical need for additional therapies beyond current PBS-subsidised medicines in a small subgroup of previously untreated patients with stage IIIb/c and stage IVM1a melanoma. The PBAC also noted that current clinical trials were evaluating the role of T-VEC as an add-on therapy to current PBS-subsidised medicines. 19PSD · Jul 2016
6.24 The submission presented a cost-minimisation analysis of T-VEC compared to ipilimumab using the full published price for ipilimumab and the proposed published price for T-VEC. The submission anticipated that the effective T-VEC price would be agreed upon if there was a positive PBAC recommendation, with the submission proposing to negotiate an effective price for T-VEC based on cost-minimisation to match the effective price of ipilimumab.PSD · Jul 2016
6.25 The claimed equi-effective doses were estimated as T-VEC 1 mL and ipilimumabPSD · Jul 2016
6.21 Based on restricting the use of T-VEC to patients with stage IIIb/c or stage IVM1a malignant melanoma, the submission described T-VEC as: similar in terms of comparative efficacy to ipilimumab, pembrolizumab, and nivolumab; similar in terms of terms of comparative safety to pembrolizumab and nivolumab; and having a favourable safety profile compared to ipilimumab.PSD · Jul 2016
6.22 The submission’s claims were not adequately supported. Given that the submission did not present statistical comparisons and that the trial populations were considerably different, it was not possible to form any view on the comparative efficacy or safety of T-VEC compared to pembrolizumab, nivolumab or ipilimumab from the data presented.PSD · Jul 2016
6.2 The PBAC noted and welcomed the input from health professionals (2) and organisations (2) via the Consumer Comments facility on the PBS website. The comments described a range of perceived benefits of treatment with T-VEC including the loco-regional control of melanoma, and as an extra treatment option in patient management.PSD · Jul 2016
6.45 The sponsor indicated a willingness to undertake a risk sharing arrangement to account for the uncertainty surrounding the average number of vials of T-VEC that will be used in clinical practice. The submission did not provide any details of the potential risk sharing arrangement.PSD · Jul 2016
Cost-effectiveness
Cost-minimisation analysis presented but PBAC considered there was insufficient basis for it as the submission did not establish whether T-VEC was inferior or non-inferior to ipilimumab. No numeric ICER stated.
Decision context
PopulationAdults with unresectable stage IIIb/c or stage IVM1a (stage III or IV without visceral metastases) malignant melanoma, stratified by BRAF V600 mutation status, who have undergone surgery and have not received prior ipilimumab or PD-1 inhibitor therapy.
Risk sharingSponsor indicated willingness to undertake a risk sharing arrangement to account for uncertainty surrounding the average number of vials of T-VEC that will be used in clinical practice, but no details were provided.
Why it was knocked back
- Highly uncertain magnitude of clinical benefit, highly uncertain cost-effectiveness compared to nominated comparators, insufficient basis for cost-minimisation analysis, inability to establish non-inferiority to ipilimumab, complexity of administration requiring specialist centres
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Jul 2016 | Not recommended | ipilimumab (for pricing purposes); pembrolizumab, nivolumab, BRAF/MEK inhibitors, and intra-lesional BCG also considered | — | RCT · Durable response rate |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| Study 002/03 | Ph 2 | 3 | Number of Participants With Adverse Events | completed |
Consumer voice
Health professionals and organisations highlighted perceived benefits of T-VEC including loco-regional control of melanoma and a new treatment option. Key points noted were good tolerability, novel mode of action, overall survival benefit in early stage metastatic melanoma, and the need for patient education on handling a live virus product.
The comments described a range of perceived benefits of treatment with T-VEC including the loco-regional control of melanoma, and as an extra treatment option in patient management. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to stage III/IV without visceral metastases, first-line, and no prior ipilimumab or PD-1 inhibitor therapy; TGA label is broader.