Linzagolix
Treatment of symptomatic uterine fibroids in adult premenopausal women who are unsuitable for, or have had an inadequate response to prior hormonal therapies.
Decision on record
- Meeting Jul 2024 Not recommended Moderate to severe symptomatic uterine fibroids
From the public summary
The PBAC did not recommend the listing of linzagolix for the treatment of symptomatic uterine fibroids. The PBAC noted that there were safety concerns regarding bone mineral density (BMD) loss, particularly at the higher 200 mg dose without add back hormonal therapy (ABT), and that in the short term, ABT did not fully ameliorate that risk. The PBAC also noted that long-term safety data with ongoing linzagolix treatment is currently limited.PSD · Jul 2024
The primary reason for this outcome was due to the economic evaluation.PSD · Jul 2024
The submission presented a stepped economic evaluation of linzagolix versus BSC, based on results from the linzagolix 200 mg + ABT and placebo arms of pooled PRIMROSE 1 and 2 data plus external sources. As discussed, this was not an accurate representation of a second line setting in Australia which would also include hormone treatments as part of BSC with or without tranexamic acid, both of which were specifically excluded.PSD · Jul 2024
Outcomes Quality-adjusted life years Appropriate. 3 years to 21 years (based on cohort starting The ESC considered that this was not reasonable. The ages 35, 39, 43, 46 with percentages from model did not include patients younger than 35 years.PSD · Jul 2024
The submission described linzagolix (100 mg or 200 mg) ± ABT as superior in terms of effectiveness compared to BSC (consisting of either NSAIDs and/or iron supplementation). The evaluation considered the claim may not be appropriate for patients who have had an inadequate response to prior hormone therapy as patients 27PSD · Jul 2024
Overall, the ESC considered that for the patients enrolled in the trials, the evidence supported the claim that linzagolix was associated with a reduction in menstrual blood loss, haemoglobin/anaemia, pain and improvement to symptom severity compared with placebo.PSD · Jul 2024
The Sponsor indicated willingness to work with the Department of Health and Aged Care on an appropriately formulated and structured RSA. For more detail on PBAC’s view, see section 7 PBAC outcome.PSD · Jul 2024
Cost-effectiveness
ICER value not stated in the publicly available text; economic evaluation was conducted but specific ICER figures are not printed in this PSD extract.
Decision context
PopulationAdult premenopausal women (at least 18 years old) with moderate to severe symptomatic uterine fibroids confirmed by ultrasound (at least one fibroid ≥2 cm in diameter or multiple fibroids) with significant heavy menstrual bleeding negatively affecting quality of life, who are unsuitable for or have had inadequate response to prior hormonal therapies (progestins or progestin-estrogen combinations).
Why it was knocked back
- Significant safety concerns regarding bone mineral density loss with long-term GnRH therapy, particularly in younger women; unclear clinical benefit profile with high placebo response; trial design did not reflect Australian second-line clinical practice; population restrictions lacked clarity and specificity; BMD monitoring requirements not adequately addressed; requested restrictions did not align with trial inclusion/exclusion criteria; limited long-term efficacy and safety data (maximum 1 year); TGA Delegate concluded benefit-risk profile was uncertain
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Jul 2024 | Not recommended | best supportive care | — | RCT · MBL |
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to premenopausal women, moderate-severe HMB, fibroid size ≥2cm, and prior hormonal therapy failure; TGA label has no such restrictions.