Drawing on data from two large Phase 3 clinical trials of endometriosis-related pain, AbbVie demonstrated that its oral drug candidate elagolix (ABT-620) improved patients’ impressions of pain as well as their quality of life.
In addition, the treatment is likely to be less expensive than surgical interventions for endometriosis, as an additional study by Abbvie showed that total healthcare costs for patients managed with surgery are higher than costs for patients receiving non-surgical care.
The data was presented at the American Society for Reproductive Medicine (ASRM) 2016 Congress, held in Salt Lake City, Utah, on Oct. 15–19.
Elagolix is an oral gonadotropin-releasing hormone blocker, which subdues estrogen production through its actions on other reproductive hormones.
Two trials – one goal
The Phase 3 studies (NCT01620528 and NCT01931670) of elagolix, the largest endometriosis trials to date, included 1,686 premenopausal women who were randomized to receive either 150 mg Elagolix once daily, 200 mg twice daily, or placebo.
Women in the trial, ages 18-49, had been surgically diagnosed with endometriosis in the 10 years before the study’s start, and had moderate-to-severe endometriosis-associated pain.
The first study focused on a North American population and enrolled 871 patients, while the second trial also included patients in North America, Europe, Australia, New Zealand, Brazil, and South Africa, with 815 women participating. In the first study, 75% of participants completed the study. In the second, the proportion was 77%.
Both studies explored how six months of treatment impacted menstrual and non-menstrual pelvic pain — the trials’ main outcome measure. As reported earlier by Endometriosis News, Elagolix effectively lowered both types of pain. Researchers, however, also investigated more personal aspects of pain.
Pain can be measured in numerous ways
For evaluation of the women’s perspective on pain improvement, researchers used three rating scales, allowing women to report how they felt using an electronic diary. Endometriosis-associated pain was reported using a 10-point scale, in which women rated their daily pain from none to worst.
A screening for dyspareunia, or pain related to sexual intercourse, used a three-point grading, ranging from none to severe. Participants also could state that the issue was non-applicable. Finally, the Patient Global Impression of Change was reported once a month, and rated changes in perceived pain on a seven-point scale ranging from very much improved to very much worse.
Both studies showed that endometriosis-associated pain decreased after three and six months of treatment. Also, more women treated with elagolix reported much, or very much, improvement in the Patient Global Impression of Change score than those receiving placebo after three and six months.
Among the 76% of women who had reported pain during intercourse, only those treated with the 200 mg twice daily dose experienced a statistically significant improvement after six months compared to placebo.
As with the majority of the drug’s effects, improvements were dose-dependent, meaning that the higher dose produced more robust effects. This is understandable since studies have shown that the higher dose suppressed estrogen production almost totally.
Quality of life
The pain experienced by women with endometriosis takes its toll on life quality. To explore if the harnessing of pain by elagolix extended to other aspects of daily life, researchers asked participants to complete the Endometriosis Health Profile, also known as EHP30.
This self-administered questionnaire explores pain, control and powerlessness, social support, emotional well-being, self-image, and sexual intercourse. For each question, women report how they perceive a situation on a scale ranging from 0 (never) to 4 (always).
Findings showed that elagolix-treated patients had more quality-of-life benefits at both three and six months, compared to those receiving placebo. The effects, again, were greater with the higher dose that triggered an improvement in all aspects of the survey. The lower dose did not improve ratings of self-image and sexual intercourse.
“Our data showed that elagolix not only reduced pain, but it also improved several measures of quality of life, including emotional well-being and self-image,” Dr. Hugh S. Taylor with Yale Fertility Center of New Haven and the study’s leading author, told Endometriosis News. “There have been few recent scientific advancements for patients suffering from endometriosis, and endometriosis-associated pain is currently managed with treatments such as oral contraceptives, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids and GnRH agonists, many of which are not specifically indicated for the treatment of endometriosis. None have been demonstrated to improve all of these important measures of quality of life.”
The cost of treatment
In contrast to the elagolix data, analyses of healthcare costs did not focus on the two Phase 3 trials. Instead, researchers used claims databases, in which all details that would allow identification of patients had been removed.
Researchers identified 124,530 women, ages 18-49, who had undergone an hysterectomy (removal of the uterus), oophorectomy (removal of ovaries), or a laparotomy or laparoscopy (both abdominal surgery methods) for their endometriosis.
Researchers included only women who had not had surgery but had been diagnosed with endometriosis on at least two occasions, to reduce the risk of including misdiagnosed patients. They identified 37,106 non-surgery patients.
The study assessed both direct costs of surgery, and both direct and indirect costs during a 12-month period before and after surgery.
Before surgery, costs were lower in the group that would be operated on later. The cost of the surgery itself was highest for removal of ovaries, followed by uterus surgery, traditional, and keyhole abdominal surgery.
As patients underwent surgery, the total costs increased, becoming higher than in patients not undergoing surgery. The type of costs varied between different types of surgery, with patients who had an ovary procedure having higher total healthcare, endometriosis-related, and indirect costs due to short-term disability. Indirect costs caused by absence were highest among women having uterine surgery.
The total yearly indirect costs were $8,843 for surgery patients, and $5,603 for non-surgery patients.
“It’s important for patients to speak with their doctor to discuss an appropriate treatment regimen that considers the advantages and disadvantages of each treatment option. Medical therapy can obviate the need for surgery in some instances. There is no cure for endometriosis and, in more extensive cases, surgical interventions (e.g., laparotomy or laparoscopy) are often pursued, and may not be curative for all individuals,” Dr. Taylor said in the interview.
“Elagolix is currently being investigated in diseases that are mediated by sex hormones, such as uterine fibroids and endometriosis. The data presented at ASRM demonstrate that elagolix has the potential to be an important treatment option for women suffering from pain related to endometriosis.”