Obseva’s linzagolix blooms but safety questions remain

Snippets

Obseva is further behind the competition in uterine fibroids but the company’s gonadotropin-releasing hormone (GnRH) antagonist linzagolix could have the edge clinically. Results from the phase III Primrose 2 trial showed a placebo-adjusted 65% response rate for a high dose of linzagolix in combination with hormonal add-back therapy (ABT), putting it in the same league as Abbvie’s Orilissa, and slightly better than Myovant’s Relugolix, cross-trial caveats notwithstanding. The pull for linzagolix is a low dose option without ABT; ABT is needed to counteract the menopause-like symptoms associated with GnRH inhibition but has side effects of its own and is not advised in patients with high BMI, diabetes and cardiovascular disease. The company described a 27% placebo adjusted response rate for the low dose as “clinically relevant”, saying it could open up linzagolix as a first-line treatment. One potential hurdle is safety: bone loss points to greater levels than with competing projects, though Obseva claims that patient demographics could explain this. A second pivotal study, Primrose 1, will need to confirm this profile for a filing to occur next year. Tiny Obseva has its work cut out to catch up in this space, however. 

Cross-trial comparison of GnRH inhibitors in uterine fibroids

  Linzagolix (Obseva) Orilissa (Abbvie) Relugolix (Myovant)
  Primrose 2 Elaris UF-1 Elaris UF-2 Liberty 1 Liberty 2
  100mg daily w/o ABT 200mg daily* 300mg bid* 300mg bid* 40mg daily* 40mg daily*
Placebo-adjusted response rate 27% 65% 60% 66% 55% 57%
Placebo-adjusted bone mineral density change -2.50% -1.81% -0.55% -0.55% -0.41% -0.45%
*Doses with ABT; bid=twice daily. Source: company press releases, Leerink.
Responders were defined as patients with menstrual blood loss volume of less than 80mL and ≥ 50% reduction from baseline in menstrual blood loss volume at 24 weeks

 

GnRH antagonists in uterine fibroids
Product Company 2024e fibroid sales ($m) Indication status
Orilissa (elagolix) AbbVie 657 Filed in August 2019
Relumina (relugolix) Myovant/Takeda/Aska Pharmaceutical 458 Phase III (Marketed in Japan)
Linzagolix ObsEva 209 Phase III
Source: EvaluatePharma

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