Key takeaways:
- HMI-115, a monoclonal antibody, significantly reduced dysmenorrhea and pelvic pain in premenopausal women with endometriosis.
- All 3 HMI-115 dose groups showed greater pain reductions than placebo by week 12, with improvements persisting to week 24.
- Non-menstrual pelvic pain also declined, particularly in the 120 mg and 240 mg groups.
- The treatment demonstrated a favorable safety profile, with only 1 unrelated serious adverse event reported.
- Findings support advancing HMI-115 into larger, longer phase 3 trials to further evaluate its potential as a nonhormonal therapy for endometriosis-associated pain.
A recent study published in The Lancet Obstetrics, Gynecology, and Women’s Health has found tolerability and efficacy for the human monoclonal antibody HM-115 toward reducing pain in endometriosis patients.1
Endometriosis is associated with chronic pelvic pain, dysmenorrhea, infertility, painful sexual intercourse, and psychological distress.2 Inhibiting ovulation or decreasing oestrogen are the methods currently recommended for alleviating symptoms, but these options are limited.1
“A substantial unmet need exists for pharmacological interventions for endometriosis-associated pain that operate via mechanisms independent of sex hormones,” wrote investigators.
Evaluating HMI-115
The study was conducted to evaluate the safety and efficacy of HMI-115 in premenopausal women for reducing endometriosis-associated pain. The first period of the study included washout of hormone treatment if applicable. This was followed by a screening period of up to 75 days.
Baseline blood tests and examinations were performed at visit 1, while eligibility was determined at visit 2. Participants were also given an electronic diary device at this time. No restrictions were implemented for opioids or non-steroidal anti-inflammatory drugs (NSAIDs), with NSAID options including ibuprofen, naproxen, diclofenac, and celecoxib.
Opioid options included hydrocodone, codeine phosphate, and tramadol. Patients and their physicians selected the type of NSAID or opioid to administer.
Treatment protocol and visit schedule
Treatment lasted for 12 weeks in the third period of the study. Participants attended trial visits on day 1 of treatment, followed by every 2 weeks for the next 12 weeks. During these visits, treatment was provided in person at health centers. Finally, a 12-week follow-up period was performed, with the final follow-up visit at week 25.
Premenopausal women aged 18 to 49 years diagnosed with endometriosis through laparoscopy or laparotomy and with moderate to severe endometriosis-associated pain were eligible for inclusion. A total Composite Pelvic Signs and Symptoms Score of at least 6, alongside a score of at least 2 for both dysmenorrhea and non-menstrual pelvic pain, indicated moderate to severe pain.
Participants were required to be taking at least 2 nonhormonal contraceptives and were randomized at visit 3. Randomization was 1:1:1:1 to the HMI-115 60 mg, 120 mg, 240 mg, and placebo groups. These medications were administered by a study nurse through subcutaneous injection at study centers every 2 weeks during the treatment period.
Pain was recorded using the Endometriosis Daily Impact of Pain scale. Scores ranged from 0 to 3, with higher scores indicating greater pain. Additionally, menstrual bleeding was rated on a scale of 0 to 4, with higher scores indicating increased bleeding.
Efficacy outcomes across HMI-115 dose groups
There were 142 participants included in the trial, 34 of whom did not have endometriosis and were only included in an exploratory analysis. Of the remaining 108 participants, 27 received HM-115 60 mg, 27 HMI-115 120 mg, 24 HMI-115 240 mg, and 30 placebo.
Similar baseline characteristics were reported between groups, including a mean patient age of 38 years. Fifty-four percent of patients were White while 45% were Asian, and endometriosis was diagnosed through laparoscopy in 89% vs laparotomy in 11%. Only 2% of patients reported opioid use at baseline, though 81% reported NSAID use.
The following least-squares mean changes in dysmenorrhea numerical rating scale (NRS) scores between baseline and week 12 were reported:
- -2.57 in the HMI-115 60 mg group
- -3.29 in the 120 mg group
- -3.26 in the 240 mg group
- -2.31 in the placebo group
Mean percentage changes in dysmenorrhea NRS scores from baseline to week 12 were -27.35%, -34.72%, and -41.57% among the 60 mg, 120 mg, and 240 mg groups, respectively. Persistent reductions in NRS scores were also reported for these groups at week 24.
Safety and implications
Non-menstrual pelvic pain scores also declined in these groups, with the HMI-115 120 mg and 240 mg groups reporting the greatest reductions. Only 1 serious adverse event of a breast nodule was reported in the HMI-115 240 mg group, which was unrelated to the study treatment. Overall, these results highlighted the safety and efficacy of HMI-115 toward reducing endometriosis-associated pain.
“These findings support further evaluation of HMI-115 in phase 3 studies with more participants and for a longer duration,” wrote investigators.
References
- Zhu L, Chen Z, Liu H, et al. Safety and efficacy of subcutaneous injection with HMI-115 versus placebo in endometriosis-associated pain in premenopausal women: a multicentre, double-blind, randomised, proof-of-concept phase 2 trial. The Lancet Obstetrics, Gynecology, and Women’s Health. 2025;1(3):E174-E188. doi:10.1016/j.lanogw.2025.100032
- Soliman AM, Yang H, Du EX, et al. The direct and indirect costs associated with endometriosis: a systematic literature review. Hum Reprod. 2016;31:712-722.
