For these patients who have few effective treatment options, there is great opportunity for novel drugs to have a big impact on outcomes and quality of life. With Relugolix, patients have an effective, oral choice, although with long-term hypoestrogeneic side effects that will need to be taken into consideration and potentially managed.
Relugolix for prostate cancer
Relugolix for endometriosis
Relugolix for uterine fibroids
Patients with prostate cancer would benefit from therapies with greater effectiveness, targeting predictive biomarkers with new MOAs and that prevent or delay progression to CRPC.
“Relugolix could be a huge game changer. …with Firmagon, there was a retrospective paper that showed less cardiovascular toxicity. Giving an agonist increases risks of heart attacks and cardiac death, but Firmagon will reduce this. To have an oral antagonist sounds amazing. I don’t think you could use relugolix for everybody…it is going to be more expensive than current therapies…a lot of men like having a three- or six-monthly injection over a daily tablet, but for those who have had a cardiovascular event or high-risk cardiac, I think you could probably…work out that you are actually saving money.”
There are few safe, long-term medical treatments, particularly non-hormonal or non-invasive options, for the management of endometriosis-related pain.
Many treatments have undesirable menopause-like side effects (hot flashes, headache, nausea). Due to an increasing proportion of women delaying childbearing until later in life, there is also demand for uterus-sparing treatments.
“Using birth control pills continuously can help the majority of the endometriosis-related pain. GnRH antagonists are likely to be used in the second line following birth control pills, and they have the potential for long-term use.”
There are few safe, long-term medical treatments for uterine fibroid management, and rebound fibroid growth can occur once treatment ends.
Patients are reliant on therapies that are safe but less effective, are effective but with a suboptimal safety profile, or have menopause-like side effects (hot flashes, headache, nausea).
Due to an increasing proportion of women delaying childbearing until later in life, there is also demand for uterus-sparing treatments.
“I guess the only real benefit for GnRH antagonists is the fact that you can give them orally, as compared with the agonist where you have to usually use an injection. So, I think that’s the real benefit of the antagonists.”
Its potential use for three indications increases its chances of success.
The oral formulation (daily administration) provides advantages over the injectable (administered every 3 months) GnRH agonist competitors, including convenience and better management of side effects.
Demonstrated to be efficacious and comparatively safe, relugolix provides another option for medical management and might prevent or delay the need for surgical treatment.
For women with few effective medical management options for uterine fibroids and endometriosis, relugolix is promising for its efficacy and ease of use. However, long-term use of GnRH antagonists is hampered by hypoestrogenic side effects, including bone loss.
As the second-to-market GnRH antagonist for both endometriosis and uterine fibroids in the U.S., it will compete with AbbVie’s Orilissa/Oriahnn, which had combined sales of $125M in 2020.
Although it will be first to market in the E.U., it is a smaller commercial opportunity.
Its uptake for prostate cancer will likely be modest, despite its entry as the first and only GnRH antagonist approved for prostate cancer, owing to fierce competition from the well-established GnRH agonists and Firmagon (injectable GnRH antagonist), and sales will be further constrained by the expected entry of generic alternatives.
Numerous questions remain about the launch prospects for agents in this class, but signals of therapeutic potential from completed studies indicate clinical success in early Alzheimer’s disease remains possible with optimized treatment dosing and duration.