Elagolix

Unassigned

New Medicines

OriahnnMenorrhagia associated with uterine fibroids in premenopausal women (combination with estradiol and norethindrone acetate)

Information

Oriahnn
New formulation
AbbVie
Neurocrine Biosciences

Development and Regulatory status

PII Clinical trials
None
Approved (licensed)
May 20Approved in the US as Oriahnn (an oestrogen and progestin combination product consisting of elagolix, estradiol and norethindrone acetate) capsules, co-packaged for oral use, for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women. Launch planned for Jun 20. Elagolix is also available in the US as Orilissa for treatment of endometriosis [14].
Feb 19Abbvie currently has no plans to launch in UK [13].
Nov 18Company announce plans for FDA New Drug Application submission in mid-2019 [12]
Jan 16PIII trial programme started [5].
Sep 15AbbVie and partner Neurocrine Biosciences are planning to launch a PIII trial of their uterine fibroid treatment elagolix in early 2016 after tracking a positive effect in PIIb [6]

Category

First-in-class oral gonadotropin-releasing hormone (GnRH) antagonist that allows partial oestrogen suppression
At least 1 in 4 women develop one or more fibroids in their lifetime. They usually develop in women aged 30-50. Fibroids are more common in women from Afro-Caribbean origin and in women who weigh over 70 kg (11 stones)
Menorrhagia associated with uterine fibroids in premenopausal women (combination with estradiol and norethindrone acetate)
Oral

Trial or other data

Mar 19An extension safety and efficacy study initiated in Sep 2016 in the US, Canada and Puerto Rico, ELARIS UF-EXTEND (NCT02925494; n=433) was completed. Topline results from the trial were reported in Aug 2018 by AbbVie. The primary and secondary endpoint data from the extension study were consistent with that observed in the two pivotal phase III studies [15].
Nov 18Additional data from 2 x PIII clinical trials (ELARIS UF-1 and ELARIS UF-2) for elagolix in women with uterine fibroids. After 6 months, elagolix (300mg BD + lestradiol 1.0 mg / norethindrone acetate 0.5 mg) reduced heavy menstrual bleeding associated with uterine fibroids vs. placebo. In ELARIS UF-1 and ELARIS UF-2, 68.5% and 76.2% (both p<0.001) of pts achieved clinical response vs. 8.7% and 10.1% on placebo respectively. Clinical response was defined as menstrual blood loss volume 50% reduction in menstrual blood loss volume. Around 50% of women in both studies achieved amenorrhea after 6 months treatment and pts reported improvement in symptom severity and quality of life. The overall safety profile was consistent with that observed in PII studies and no new safety signals were identified. Frequent adverse effects were hot flush, nausea, headache, night sweats and fatigue.[12]
Mar 18PIII ELARIS UF-II trial (NCT02654054) meets primary endpoint. Study showed 76.2% of women achieved a clinical response (defined as menstrual blood loss volume of less than 80 mL during month six and a 50% or greater reduction in menstrual blood loss volume from baseline to month six) compared to 10.1% for placebo (p<0.001) [11].
Feb 18PIII ELARIS UF-1 trial (NCT02654054) meets primary endpoint. At six months, elagolix, in combination with low-dose hormone therapy, reduced heavy menstrual bleeding in 68.5% women with fibroids compared to 8.7% in placebo group as measured by alkaline hematin method. AbbVie plan to seek FDA approval once a second study has completed [10].
Jan 18Estimated primary completion date Mar 19 for NCT02925494 and Jan 18 for NCT02654054 [9].
Sep 16Extension safety and efficacy study (NCT02925494) initiatd. Study aims to evaluate elagolix in the treatment of uterine fibroids. Primary endpoint will be percent of patients with reduction in uterine blood flow as measured by the alkaline haematin method. Bone mineral density will be evaluated via DXA scan at baseline, the conclusion of dosing and six months post-dosing. The trial is enrolling participants by invitation only, in the US and Canada. Estimated primary completion date Jan 19 [7,8].
Jan 16Recruitment to second PIII trial (NCT02691494) started. The placebo-controlled randomised trial is expected to enrol approximately 400 patients, following which the participants may enter a six-month safety extension study. Primary efficacy endpoint is an assessment of the change in menstrual blood loss utilising the alkaline hematin method at 6 months compared to baseline. Estimated primary completion date is July 18 [7,8].
Jan 16Recruitment to the first of two planned PIII trials (NCT02654054) started. The placebo-controlled randomised trial aims to to evaluate efficacy, safety and tolerability of elagolix alone and in combination with oestrogen plus progestogen for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women. Primary efficacy outcome is Percentage of Responders based on menstrual blood loss (MBL) volume reduction at 6 months. This study appears to be recruiting in the US only; estimated primary completion is May 2018 [5,6].
Sep 15AbbVie & Neurocrine Biosciences announce completion of a P2b trial evaluating the safety and efficacy of elagolix alone or in combination with add-back therapy compared to placebo. The trial was conducted in women with heavy menstrual bleeding (HMB) associated with uterine fibroids. Preliminary results showed that all of the elagolix treatment arms, with and without add-back therapy, reduced heavy menstrual bleeding vs. placebo (p<0.001). The study´s primary endpoint was a composite design where subjects had to achieve a menstrual blood loss (MBL) volume of less than 80 mL as well as a 50% or greater reduction in MBL volume from baseline at the final study month as measured by the alkaline hematin method [6].
Mar 15Still in PII for uterine fibroids [3].
Mar 13A PIIb clinical trial to evaluate elagolix has started. The 6 month randomized, double-blind, placebo-controlled study will enrol 280 subjects with heavy uterine bleeding due to uterine fibroids. The primary efficacy endpoint is an assessment of the change in menstrual blood loss utilizing the alkaline haematin method. Secondary endpoints include the change in fibroid volume and Hb. BMD will be assessed via DXA scan at baseline, the conclusion of dosing, and six months post-dosing [2].
Sep 11PII study evaluating the effects of elagolix for uterine fibroids started [1]