Orilissa (elagolix) has won U.S. regulatory approval as the first oral therapy in a decade for moderate to severe pain linked to endometriosis — a disease that plagues 10 percent of all women of reproductive age.
The therapy, developed by Chicago-based AbbVie in cooperation with Neurocrine Biosciences, was approved by the U.S. Food and Drug Administration and is expected to be available in retail pharmacies early next month.
The FDA based its decision on data from two studies in the largest endometriosis Phase 3 clinical trial program ever conducted. The two nearly identical studies (NCT01620528 and NCT01931670) included 1,689 women with moderate to severe endometriosis pain.
They showed that three out of four women on 200 mg of Orilissa twice a day — the higher of two doses compared with placebo — saw a significant reduction in the three most common types of pain associated with the disease: daily menstrual pelvic pain, non-menstrual pain, and pain during sex.
But both doses given in the trials — 150 mg once daily and 200 mg twice daily — eased these types of pain with clinical significance. The FDA approved the use of both doses, the higher dose for up to six months of use and the lower dose for up to 24 months.
Another Phase 3 trial, (ELARIS UF-II; NCT02691494), evaluated Orilissa’s potential to treat uterine fibroids. Its researchers reported that, when combined with low-dose hormone therapy, the experimental drug reduced heavy menstrual bleeding.
“Orilissa represents a significant advancement for women with endometriosis and physicians who need more options for the medical management of this disease,” Michael Severino, MD, AbbVie’s executive vice president of research and development, said in a press release.
Severino, also the company’s chief scientific officer, noted that endometriosis affects one in 10 women of childbearing age, and that women can suffer for up to 10 years and visit multiple physicians before receiving a proper diagnosis.
Orilissa is a nonpeptide small-molecule gonadotropin-releasing hormone (GnRH) receptor antagonist that prevents endogenous GnRH signaling by binding to GnRH receptors in the pituitary gland.
The treatment is not without risks, however. AbbVie noted that Orilissa can cause serious side effects, including decreased bone mineral density and suicidal thoughts, actions, or behaviors, as well as mood swings.
In the pivotal Phase 3 studies, Orilissa was linked in a dose-dependent manner to lower bone mineral density after six months of use, a likely reason for the FDA to more strictly limit the 200 mg dose — it caused a larger drop in bone density. The higher dose also gave rise to a larger proportion of patients who had a more than a 3 percent drop in spine bone density.
Its use may also lead to liver problems, but the most common side effects are hot flashes, night sweats, headaches, nausea, difficulty sleeping, absence of periods, and joint pain.
Tamer Seckin, MD, founder and medical director of the Endometriosis Foundation of America, called the FDA’s approval of Orilissa “truly incredible news.”
But he also offered a few caveats in a phone interview from New York.
“We should be cautiously optimistic on how it will benefit these patients,” he told Endometriosis News. “We know that when the disease has lasted for many years, at that advanced stage if the disease is not removed, these medications do not have very good outcomes.”
Seckin stressed that Orilissa is “not a treatment, it’s a management medicine” — and that the general public needs to know the difference.
“Pain is an incredibly complex issue, because it’s perceived in our cortex. These medications don’t really eradicate the disease or make the lesions disappear,” he said. “However, I’m optimistic that they will have some effect on some groups of patients who will find relief.”
“As a clinician and a surgeon, I want to emphasize that the primary step [in eradicating endometriosis] is removing the lesions as completely as possible. There’s no exception to this,” Seckin added.
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