A new, safer drug has been developed that could revolutionise the way clinicians treat some of the most common gynaecologic diseases including fibroids and endometriosis. A clinical trial published in the Lancet found that linzagolix, an oral drug that hinders oestrogen production, is an effective and customisable treatment for fibroids. Not only does linzagolix ease symptoms but also shrinks the fibroids themselves.
Professor Hugh S. Taylor, MD, co-author of the paper, said: “No treatments to date for fibroid growth are something I would ever want my patients to take for a prolonged period of time, as they did not treat the underlying cause of the problem. This is an extremely well tolerated class of drugs that can control fibroid growth. We’ve never had anything like that before.”
The suffering and inconvenience caused by uterine fibroids can have a serious impact on quality of life. “This can be an impediment to getting a good night’s sleep and being socially active, and it can even affect job performance,” said Prof Taylor.
As fibroids grow larger, they may begin putting pressure on other organs, resulting in a range of unpleasant symptoms including diarrhoea or constipation and frequent urination. Fibroids can also lead to difficulty in getting pregnant and increased risk of miscarriage. They are more common and aggressive in black patients.
Most drugs commonly used for uterine fibroids, including birth control pills, do not treat the fibroids themselves and just lighten or stop periods. And more aggressive drugs, although they treat the root of the problem are “overkill” Prof Taylor said. For example, leuprolide is an injectable drug that puts patients into a menopausal state by initially overstimulating hormonal receptors, which eventually shuts them down and completely blocks oestrogen production. Although the treatment addresses the fibroids, it also can initially exacerbate symptoms and cause harsh side effects. In more extreme cases, patients may opt for hysterectomy.
Promising clinical trial results
Linzagolix is an oral medication that works similarly to leuprolide by hindering hormone production. However, unlike its predecessor, it works by directly blocking the receptors instead of overstimulating them. The drug is also titratable, allowing reduction of oestrogen production without initiating menopause.
The new drug may however cause menopause symptoms such as hot flashes, with hormonal add-back therapy an option for mitigating these symptoms. For some patients, however, including patients with obesity, hypertension, or diabetes, this therapy has risks and may not be a suitable option. These conditions also tend to be more prevalent in Black patients. In this group, a lower dose of linzagolix without add-back therapy might be preferable.
To test the effectiveness of the drug, Prof Taylor’s team ran two large prospective, randomised, double-blind, placebo-controlled clinical trials known as PRIMROSE 1 and PRIMROSE 2. The studies enrolled patients suffering from substantial bleeding who were randomised to placebo or one of several different doses of the drug: 100mg alone, 100 mg with add-back therapy, 200mg alone, or 200mg with add-back therapy. Patients were followed for one year. The researchers considered the therapy successful if the patient’s bleeding was reduced by half and also stayed in what is considered the normal range.
Patients in all four treatment groups experienced a significant reduction in menstrual bleeding. The 200 mg with add-back therapy group worked with “amazing efficacy,” said Prof Taylor: the clinical trials showed a 75.5% response rate in PRIMROSE 1 and a 93.9% rate in PRIMROSE 2. Even the lower dose of the drug still showed promising results. There were greater than 60% response rates in both trials for the 100mg group with add-back therapy, and the 100mg group without add-back showed better than 50% response rates.
“What is interesting and unique about our trials, that has not been done with other drugs in this class, is that we used a low dose with or without hormones,” said Prof Taylor. “This is a great option for patients who experience severe menopause symptoms from the high dose or have a medical problem where they can’t tolerate hormonal add-back therapy.”
Changing the treatment of gynaecologic disease
Linzagolix is one of several in this new class of drugs in development for the treatment for common gynaecologic diseases. Prof Taylor was also involved in the 2017 clinical trial for elagolix, a medication designed to suppress endometriosis that has recently become available for patients.
Linzagolix has so far been approved in Europe. Taylor says drugs in this class will radically change how clinicians treat fibroids, and he hopes linzagolix will lead to a reduction in future hysterectomies once it becomes available.
“A good medical therapy is finally here for fibroids, and I predict that what was a very common operation will dramatically decrease within the next few years,” he says. “Reducing the need for hysterectomy is very important for patients who don’t want to undergo a major surgery, especially for younger people who may still want to preserve the potential of having children in the future.”
Source: Yale University
