FDA approves elagolix (Orilissa), the first and only oral treatment for endometriosis pain

The U.S. Food and Drug Administration (FDA) today approved ORILISSA™ (elagolix), the first and only oral gonadotropin-releasing hormone (GnRH) antagonist especially useful in the management of women with moderate to severe endometriosis pain— announced AbbVie and Neurocrine Biosciences.

Orilissa represents the first FDA approved oral treatment for endometriosis in over a decade and is expected to be available in U.S. retail pharmacies in early August 2018.

The drug is available in two oral dosages-150 mg once daily and 200 mg twice daily, taken with or without food roughly at the same time every day.

The FDA approval is supported by the results of 2 of the largest, randomized, double-blind, placebo-controlled phase 3 trials conducted to date, which evaluated nearly 1,700 women with moderate to severe endometriosis pain. Women either received 150 mg, 200 mg (952 women) or a placebo (734 women) and were evaluated at the end of 3 months.

Of the women in the treatment arm, 475 received a 150-mg daily dose, while and 477 received a 200-mg twice-daily dose.

Clinical trial results demonstrate that Orilissa significantly reduced all the 3 types of pain commonly associated with endometriosis— daily menstrual pelvic pain, non-menstrual pelvic pain, and pain with sex (p <0.001). Furthermore, women on 200 mg dose showed a significant reduction in dyspareunia as compared to placebo.

The most significant side effect observed with elagolix is dose-dependent decreases in bone mineral density; limiting the treatment to either 150 mg daily for up to 24 months or 200 mg twice daily for up to 6 months.

Bone mineral density loss is not entirely reversible on stopping the treatment. Other adverse effects are reported in 5% of patients and include hot flashes/night sweats, headache, and nausea, difficulty sleeping, an absence of periods, anxiety, joint pain, depression and mood changes.

"ORILISSA represents a significant advancement for women with endometriosis and physicians who need more options for the medical management of this disease," said Michael Severino, M.D., Executive Vice President, Research and Development and Chief Scientific Officer, AbbVie. "The approval of ORILISSA demonstrates AbbVie's continued commitment to address serious diseases and unmet needs."

"Endometriosis is often characterized by chronic pelvic pain that can impact women's daily activities," Hugh Taylor, MD, study investigator from Yale University School of Medicine in New Haven, Connecticut, said in the release. "Women with endometriosis may undergo multiple medical treatments and surgical procedures seeking pain relief, and this approval gives physicians another option for treatment based on a woman's specific type and severity of endometriosis pain."

AbbVie is going to role in an application for the approval of elagolix in Uterine Fibroids too; the drug has already shown promising results in initial trials conducted by the drug manufacturer.

AbbVie press release

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News from ACOG 2018: Elagolix promises long-term safety and efficacy in the treatment of Endometriosis

Elagolix, The first oral drug Elagolix showed promising results in the treatment of three types of pain in endometriosis reports the results of a study presented at the annual clinical and scientific meeting of the annual American College of Obstetricians and Gynecologists at Austin, Texas.

Elagolix, is a gonadotropin-releasing hormone (GnRH) receptor antagonist manufactured by AbbVie, a global research and development-based biopharmaceutical company in cooperation with Neurocrine Biosciences, Inc.

“There have been no new medications approved for a long time for systematic endometriosis and there is a huge gap because the current options are expensive, and they are often injectable drugs,” said presenter Dr. Surrey.

In this extension of an earlier phase3 trial, women with moderate to severe endometriosis-related pain who participated in the initial randomized, placebo-controlled trial were given either a 150- or 200-mg dose of Elagolix (NCT01620528).

About 569 women from 149 locations continued the treatment during the extension phase of 12 months to study the safety and efficacy of Elagolix over prolong period.

The average age of each patient group was between 31 and 34 years, and all groups were majority white, with a mean length of time from surgical diagnosis ranging from 45.5 to 56.6 months.

Patients reported a decrease in daily analgesic use by 46%-77% and improvement in dysmenorrhea and chronic pelvic pain by 49%-53% with 150 mg dose and by 82% for those at 200 mg.

Common side effect reported during the extension period was hot flashes, but they were not as severe as GnRH analogs and did not require any additional treatment. GnRH analogs are current gold standard for endometriosis and cause severe hot flashes requiring additional treatment.

The drug is also being evaluated in the treatment of uterine fibroids.

FDA is already on Elagolix and has announced April 2018 that it requires extended time to review additional information regarding the results of liver function tests provided by AbbVie in connection with its New Drug Application (NDA) for Elagolix in endometriosis-associated pain.

" We are pleased with the outcomes of the pivotal trials thus far. AbbVie will continue to pursue Elagolix as a potential new treatment for the disease's most common symptoms, including pain related to menstruation and chronic pelvic pain throughout the menstrual cycle," said Michael Severino, the chief scientific officer at AbbVie, at the time.

Abstract

FDA release 

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Elagolix shows promising results for long term treatment of endometriosis

Elagolix has the potential to be an important treatment option for long term medical treatment for Endometriosis, reports the results of two replicate, randomized double blind, phase III studies. The paper was presented at the 13th World Congress on Endometriosis in Vancouver, Canada and simultaneously published in the New England Journal of Medicine.

Elagolix is an oral gonadotropin-releasing hormone (GnRH) receptor antagonist. It results in rapid, reversible, dose-dependent inhibition of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, leading to reduced ovarian production of the sex hormones, oestradiol and progesterone, while on therapy.

Medical management of Endometriosis requires treatment for extended period and physicians currently have very limited options in this regard. Treatment with gonadotropin-releasing hormone (GnRH) agonists, such as leuprolide acetate cannot be extended beyond 6 months because of osteoporosis and sever vasomotor symptoms.

These two-trial recruited 1,689 premenopausal women between the ages of 18 and 49 years, who had endometriosis and suffered from moderate to severe pain and had a z score of more than -1.5 for bone mineral density at the lumbar spine, femoral neck, or total hip. The study participants were from 151 sites in the United States and Canada from July 2012 through May 2014 and for Elaris EM-II at 187 sites on five continents from November 2013 through July 2015.

Each woman was randomly assigned to receive 150 mg of elagolix once daily (lower-dose group), 200 mg of elagolix twice daily (higher-dose group), or placebo.

The results were evaluated in terms of proportion of women who had clinical response for dysmenorrhea and non-menstrual pain after 3 months of treatment. Other relevant clinical parameters tested were dyspareunia, use of rescue NSAIDs and opioids, dyspareunia and non-menstrual pain at 6 months of treatment.

In both the trials, women showed statistically significant response in terms of dyspareunia and non-menstrual pain at 3 months of treatment as compared to placebo. The response was sustained at 6 months of treatment for these two parameters.

Women who received the higher dose of elagolix (200 mg twice daily) had significantly better results with respect to the use of rescue analgesic agents at 3 months and 6 months, dyspareunia at 3 months, and rescue opioid use at 3 months than did those receiving placebo.

Treatment with Elagolix improved the quality of life based on the 30-item Endometriosis Health Profile dimensions in both groups as compared to placebo.

Because of its hypoestrogenic effect, more than 70% women in the trial reported adverse effect including hot flushes and changes in bone mineral density and lipid levels but the frequency differed significantly between the higher and lower dose groups.

Professor Hugh Taylor, lead author of the resulting paper said, “The idea that we now have choices with regards to the extent of oestrogen suppression is attractive, as it allows us to provide a more personalised and individualised therapy.”

“With elagolix – unlike with Lupron (leuprolide acetate)– we can partially suppress oestrogen, unlike the “all or nothing” current approach,” he further added.

Elagolix is currently being investigated in uterine fibroids and endometriosis, and has been studied in over 40 clinical trials totalling more than 3,000 women. AbbVie, the makers of the drug, plans to submit a New Drug Application to the US Food and Drug Administration (FDA) for endometriosis in 2017. 

Full text of the article in NEJM can be accessed here.