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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Quick facts about Bone Health: News from ASBMR 2017 annual meeting

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The 2017 annual meeting of American Society for Bone and Mineral Research took place from September 8-11 at Denver, Colorado, USA.

It is world’s largest and most diverse meeting in the bone, mineral and musculoskeletal research field.

Some interesting facts about bone health:

Bone mass peaks around age 30 and slowly starts to decline, the rate of loss accelerated in the first few years after menopause.

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Experts recommend testing for BMD in women who have suffered any fracture at age 45 or older and at age 50 for women who have a family history of hip fractures or other bone-related disease.

All women above the age of 65 should have a baseline BMD testing done. However, after a fracture 4 out of 5 women over 67 are not treated or tested for osteoporosis.

US and other countries round the globe will see a steep rise in osteoporotic fractures because of rise in aging population. Nearly 1 in 3 women and 1 in 5 men over the age of 50 will suffer an osteoporotic fracture.

Osteoporosis affects nearly 10 million Americans while another 34 million have low bone mass predisposing them to fracture risk.

Worldwide a fragility fracture occurs every 3 secs, amounting to more than 8.9 million fractures annually.

Institute of Medicine recommends that adults 19 years of age and older require about 600-800 International Units of vitamin D daily and 1000-1200 mg. of calcium daily through food and with supplements if needed.

By 2050, the worldwide incidence of hip fracture in men is projected to increase by 310% and 240% in women, compared to rates in 1990.

NAMS updates its position statement on HRT, clearing five critical areas of confusion.

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The North American Menopause Society has updated its position statement regarding menopausal and post-menopausal hormone therapy, replacing the earlier statement issued in 2012.

Instead of prescribing, “lowest dose for the shortest period of time” which may be harmful for some women, the new emphasis is on “appropriate dose, duration, regimen, and route of administration that provides the most benefit with the minimal amount of risk.”

The new position statement was published online June 21 in NAMS’s Journal Menopause.

Hormone Replacement Therapy remains the most effective treatment for vasomotor symptoms (VMS) and Genitourinary symptoms of menopause (GSM) and helps prevent osteoporosis and fractures.

The US FDA approved indications for starting HRT are bothersome vasomotor symptoms and genitourinary symptoms, Estrogen deficient states caused by premature ovarian insufficiency (POI), hypogonadism and castration and prevention of bone loss.

Women who are seeking relief for bothersome vasomotor symptoms are offered conjugated equine estrogen (CEE) if they already had hysterectomy or it is paired with a progestogen or with bazedoxifene, a selective estrogen-receptor modulator (SERM), to protect users against endometrial cancer.

The statement authors also suggest that micronized progesterone at a dose of 300 mg at bedtime can be an effective treatment to reduce hot flashes and night sweats and improves sleep.

Low dose, intravaginal estrogen preparation is the treatment of choice for women with vulvovaginal atrophy (VVA), because of minimum systemic absorption. For women who are intolerant to estrogen, ospemifene or intravaginal DHEA is equally effective in relieving the symptoms of atrophy. This preparation also bring relief from urinary symptoms.

Systemic Hormonal therapy is not effective in improving urinary incontinence and on the other hand may exacerbate stress incontinence.

HRT in women who have undergone surgical menopause or POI should be started early and at least continued till the age of 52 years.

An important update in this statement was about starting HRT in women with BRCA 1/2 mutation. Dr. JoAnn V. Pinkerton, NAMS executive director said, "For BRCA-positive women without breast cancer who have undergone risk-reducing bilateral salpingoophorectomy, observational data suggest that systemic HRT to the median age of menopause may decrease health risks associated with premature loss of estrogen without increasing breast-cancer risk. "

Physician should be cautious in starting HRT in women who are 10 years past menopause or 60 years old at the time of initiating HRT. In these group of women, the benefit/risk ration is less favorable than for younger women because of increased risk of stroke, CVD, venous thromboembolism and dementia.

If the women are already on HRT, the therapy need not be discontinued abruptly at age 60 or 65 years. It may be continued past 65 years of age for persistent hot flashes, prevention of osteoporosis, and quality-of-life issues, with an open dialogue with the patients about the risk and benefits of HRT at this age.

Once HRT is stopped, in 50% of women, vasomotor symptoms will recur, irrespective of age of starting the therapy or duration of therapy quoted the authors of the statement.

And, nearly all women, will lose [bone-mineral density], with increased risk of bone fractures and excess mortality from hip fracture," they also point out.

Dr Pinkerton added "And the risks of longer use of HRT may be minimized with the use of lower doses of both estrogen and progestogens, the use of transdermal therapies to avoid hepatic first-pass effect, or the combination of conjugated estrogen paired with the SERM bazedoxifene, which provides endometrial protection without the need for a progestogen."

NAMS has also released a patient information sheet called ‘MenoNote’ that simplify the facts and help women to decide using HRT. The ‘MenoNote’ is available on NAMS website. It can be accessed here.