Appeal type: Formulary Exception
Decision: Overturned

Diagnosis: Endometriosis
Treatment: Formulary exception for Myfembree
The insurer denied: Formulary exception for Myfembree
The denial is overturned.

The patient is an adult female who has pelvic pain from laparoscopic confirmed endometriosis. She had been on Orilissa 150 milligrams for 24 months with management of symptoms, but then the pain returned. She was increased to Orilissa 200 milligrams twice a day, but that did not help. She had surgery last year and was placed on Myfembree. This has been working to control her pain. The request is to continue. The request was denied coverage by the health plan, because she has been on GnRH (gonadotropin-releasing hormone) antagonist/agonist for a total of 24 months. This denial is being appealed.

The health plan should cover the Formulary exception for Myfembree.

The patient has not been able to have pain relief from Orilissa. She has failed the Orilissa and surgical intervention. Orilissa did not control her pain. Medical treatment options include nonsteroidal analgesics, hormonal contraceptives, gonadotropin-releasing hormone (GnRH) analogs, and aromatase inhibitors (AI). As there are no data supporting one treatment or treatment combination over another, the treatment choice involves shared decision-making with the patient and is based upon symptom severity, patient preferences, medication side effects, treatment efficacy, contraceptive needs, costs, and availability. GnRH (gonadotropin-releasing hormone) antagonists suppress pituitary gonadotropin hormone production and create a hypoestrogenic state. They are a treatment option for patients with endometriosis-related pain who do not respond to NSAIDs (nonsteroidal anti-inflammatory drugs), estrogen-progestin contraceptives, or progestins, and they are easier to dose than GnRH (gonadotropin-releasing hormone) analogs (oral versus intramuscular). Unlike GnRH (gonadotropin-releasing hormone) agonists, antagonist agents are effective immediately, do not cause an initial surge in luteinizing hormone and follicle stimulating hormone, and do not require 7 to 14 days for GnRH (gonadotropin-releasing hormone) suppression. The antagonists elagolix and relugolix are available in oral form. The GnRH 
(gonadotropin-releasing hormone) antagonist induces a dose-dependent hypoestrogenic state to inhibit endometriotic cell proliferation. Symptom relief and adverse events such as vasomotor phenomena, vaginal atrophy, and bone loss are also dose-dependent. Relugolix has been studied as a combination therapy (relugolix-estradiol-norethindrone [norethisterone acetate; 40 milligrams/1 mg/0.5 milligrams]) or as monotherapy (40 milligrams dose for 12 weeks) followed by combination therapy for 12 weeks (Giudice et al and Myfebree insert). Two phase-three, multicenter trials, performed across five continents, compared placebo with relugolix combination therapy (relugolix-estradiol-norethindrone [norethisterone acetate; 40 milligrams/1 milligrams/0.5 milligrams]) or delayed relugolix combination therapy (relugolix monotherapy, 40 milligrams dose for 12 weeks, followed by combination therapy for 12 weeks) in individuals with moderate-to-severe endometriosis-related pain [Giudice et al]. Across the two trials, compared with the placebo group, more patients receiving relugolix reported reductions in dysmenorrhea (75 percent versus 27 to 30 percent) and less nonmenstrual pelvic pain (58 to 66 percent versus 40 to 43 percent) at six months of follow-up. While both treatment groups experienced 
reductions in bone mineral density compared with placebo, the reductions were less than 1 percent and not considered clinically significant. Both relugolix treatments were also associated with reduced opioid use. Delayed therapy was associated with similar pain reductions but also with more hot flashes and greater loss of bone mineral density. In summary, the literature does support the use of Myfembree for the management of endometriosis. There is demonstrated safety and efficacy. This is an accepted indication and appropriate for this patient who has failed Orilissa and surgical intervention. This is a different medication that Orilissa with add back to help limit the concern for bone loss. This medication is approved for 24 months. Therefore, the patient has not been on this for 12 months yet, so continuance is supported in the literature. The health plan should cover the formulary exception.