First-in-Class Endometriosis Rx Given Green Light by MHRA

The Medicines and Healthcare Products Regulatory Agency (MHRA) has granted a licence for relugolix combination therapy (Ryeqo, Gedeon Richter) for the symptomatic treatment of endometriosis in adult women of reproductive age who have a history of previous medical or surgical treatment for endometriosis.
Relugolix is a GnRH receptor antagonist that selectively binds to the gonadotrophin-releasing hormone (GnRH) receptor to block luteinising hormone (LH) and follicle stimulating hormone (FSH). This results in less production and release of oestrogen and progesterone, in turn leading to the regression of endometriotic lesions and symptoms. The oestradiol and norethisterone acetate, known as “add-back therapy”, minimises the adverse effects of a hypo-oestrogenic state. 
The combination therapy is the first in a new class of treatment and consists of relugolix 40 mg, oestradiol 1 mg, and norethisterone acetate 0.5 mg. It is taken in a single once daily tablet. 
“With limited treatments available in the UK, relugolix combination therapy may help people take control of their endometriosis-associated pain,” said Professor Andrew Horne, director of the Centre for Reproductive Health, The University of Edinburgh, in a press release.
Intense and Crippling Pain
Endometriosis is the second most common gynaecological condition in the UK, and impacts around 1 in 10 women and people with a cervix of reproductive age. It is estimated to affect more than 1.5 million people in the UK and to cost its economy around £8.2 billion every year in healthcare costs, loss of work, and treatments. 
“The intense pain associated with endometriosis can be crippling and have a devastating impact on people’s lives, from their work to intimate relationships and mental health,” Horne said.
In its Women’s Health Strategy for England, the previous government said that NHS England was updating the service specification for severe endometriosis, which would ensure that specialist services had access to the most up-to-date evidence and advice, and would improve standards of care for women with the condition.
Potential to Address Unmet Clinical Need
The outcomes of the phase 3 SPIRIT programme informed the MHRA decision to licence the treatment. This programme comprised two replicate 24-week, multicentre, randomised, double-blind, placebo-controlled phase 3 trials: SPIRIT 1 and SPIRIT 2. 
A total of 834 patients aged between 18 and 50 years, with moderate to severe pain associated with endometriosis confirmed by direct visualisation during surgery and/or histological confirmation were enrolled into either SPIRIT 1 or SPIRIT 2.
Both studies had three treatment groups. Women were randomised to receive relugolix combination therapy for 24 weeks, or placebo for 24 weeks, or relugolix 40 mg for 12 weeks followed by relugolix combination therapy for 12 weeks. 
The researchers found that once daily relugolix combination therapy significantly improved endometriosis-associated pain and was well tolerated. Specifically, in SPIRIT 1, 75% of women responded to relugolix combination therapy for their dysmenorrhoea compared to 27% in the placebo arm. In SPIRIT 2, there were 75% dysmenorrhoea responders compared with 30% in the placebo arm.
The study authors concluded that the oral therapy had the potential to address the unmet clinical need for long-term medical treatment for endometriosis, reducing the need for opioid use or repeated surgical treatment.
In its draft guidance recommendations issued in March this year, the National Institute for Health and Care Excellence (NICE) said that relugolix combination therapy was not recommended, within its anticipated marketing authorisation, for treating symptoms of endometriosis in adults who have had medical or surgical treatment for their endometriosis. 
The manufacturer of relugolix combination therapy said that it had initiated discussions with NICE and the Scottish Medicines Consortium (SMC), with a decision around NHS availability of relugolix combination therapy expected to be published in 2025.
 
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