Follitropin AlfaBemfola
Not recommended Women's healthAuthority Required 💬 consumer voice
Treatment of women undergoing assisted reproductive technology (ART) requiring controlled ovarian stimulation. Also approved for anovulatory infertility in women unresponsive to clomiphene citrate and for stimulation of spermatogenesis in gonadotrophin-deficient men.
4
Submissions
2 resub
2016–21
On the record
—
ICER range
Not modelled
Cost basis
Decisions on record
- Meeting Nov 2021 Not recommended Assisted reproductive technology
- Meeting Jul 2021 Recommended Assisted reproductive technology, anovulatory infertility
- Meeting Nov 2018 Recommended Stimulation of follicular development
- Meeting Mar 2018 Recommended Assisted Reproductive Technology (ART); Anovulatory infertility; Infertility due to hypogonadotrophic hypogonadism
- Meeting Mar 2016 Recommended Assisted reproduction
- Meeting Mar 2015 Recommended Stimulation of follicular development
Access path
- TGA registered · Bemfola
TGA label narrower than the PBS population
- Mar 2016Recommended · restricted
vs Gonal-f (follitropin alfa)
- Mar 2018Recommended · restricted
Evidence: RCT → Cost-minimisation
- Jul 2021Recommended · restricted
Evidence: Cost-minimisation → RCT
- Nov 2021Not recommended
PBAC considered the submission's claim of superior effectiveness contradictory to TGA's biosimilar regulatory…
RecommendedDeferredNot recommended
From the public summary
PBAC outcome
The PBAC did not recommend an increase to the price of Gonal-f as it considered that the clinical claim of superior comparative effectiveness of Gonal-f to all of the follitropin alfa biosimilars was not adequately supported by the data presented in the submission. The PBAC also reaffirmed its previous advice that Gonal-f and Ovaleap should be treated as equivalent for the purposes of substitution (i.e. ‘a’ flagged in the Schedule).PSD · Nov 2021
The PBAC noted that a claim of superior effectiveness of the reference brand to the biosimilar brand would be contradictory to the decision made by the TGA and other Regulatory Agencies (e.g., EMA) under the biosimilar regulatory framework.PSD · Nov 2021
Economic analysis
The type of economic evaluation presented was a cost-effectiveness analysis, of Gonal-f versus the biosimilars for ovarian stimulation. Bemfola was used as a proxy for all the biosimilars. The evaluation considered that the use of Bemfola solely as the proxy for all biosimilars might not be appropriate.PSD · Nov 2021
The PBAC considered that the submission’s clinical evidence did not support the cost- effectiveness analysis, because there was insufficient evidence to conclude that Gonal-f is superior in terms of comparative effectiveness to biosimilar preparations of follitropin-alfa.PSD · Nov 2021
Clinical claim
The submission described Gonal-f as superior in terms of effectiveness for fertility treatment compared with biosimilar preparations of follitropin alfa, and non-inferior in terms of safety compared to the biosimilars. More specifically, the submission stated that Gonal-f resulted in significantly greater rates of clinical pregnancy, ongoing pregnancy and live birth compared with the biosimilar preparations of follitropin alfa.PSD · Nov 2021
The submission described Gonal-f as non-inferior in terms of safety compared to the biosimilar preparations of follitropin alfa.PSD · Nov 2021
Consumer comments
The PBAC noted and welcomed the input from individuals (1), health care professionals (6) and organisations (2) via the Consumer Comments facility on the PBS website. The PBAC noted the advice received from Fertility First and Access Australia as well as the other consumer comments that did not support the ‘a’-flagging of Ovaleap with Gonal-f.PSD · Nov 2021
Cost-effectiveness
Requested prices are redacted; no explicit ICER calculation was presented or discussed in the document
As a Category 3 submission, the economic analysis was not independently evaluated. PBAC · 2021
ICER uncertainEconomic model disputed
Decision context
PopulationWomen undergoing assisted reproductive technology requiring controlled ovarian stimulation; receiving medical services as described in Medicare Benefits Schedule items 13200, 13201, 13202 or 13203
Why it was knocked back
- PBAC considered the submission's claim of superior effectiveness contradictory to TGA's biosimilar regulatory framework; lack of in-vitro characterisation data; claimed superiority not biologically or clinically plausible given the mechanism of action relates to oocyte retrieval, not live birth; trials not powered to detect differences in live birth rates; inadequate patient population details; average trial participant age (32.3 years) significantly younger than Australian ART population
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Nov 2021 | Not recommended | Biosimilar preparations of follitropin alfa (Bemfola used as proxy in economic evaluation) | — | Meta-analysis · Live birth rate |
| Jul 2021 | Recommended · restricted | Gonal-f | — | RCT · Surrogate |
| Mar 2018 | Recommended · restricted | — | — | Cost-minimisation |
| Mar 2016 | Recommended · restricted | Gonal-f (follitropin alfa) | — | RCT · Other |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| NCT01121666 | Ph 3 | 460 | Number of Oocytes Retrieved (Per Protocol Population) | completed |
| NCT01687712 | Ph 3 | 1,100 | Clinical Pregnancy Rate After One Cycle of Treatment - ITT Population | completed |
| NCT03088137 | Ph 3 | 118 | Oocytes (Intention-to-Treat, ITT) | completed |
| NCT03506243 | Ph 3 | 451 | The total number of oocytes retrieved | completed |
Consumer voice
Consumer input expressed concerns about pharmaceutical and clinical differences between Ovaleap and Gonal-f, and raised issues about 'a'-flagging including administrative burden on prescribers and potential for medication errors.
The comments described a range of concerns about the pharmaceutical and clinical differences affecting patient outcomes, and quality use of medicine issues. Consumer comments · PSD
quality use of medicineaccess barrierstreatment burden on prescriberspharmaceutical differencesmedication safety
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts ART indication to women with specific MBS items (13200-13203), narrowing the broad TGA label.