October 19, 2021: “Myovant Sciences and Pfizer announced the presentation of new data from clinical studies of its once-daily relugolix combination therapy (relugolix 40 mg plus estradiol 1.0 mg and norethindrone acetate 0.5 mg) in premenopausal women with uterine fibroids and in women with endometriosis pain (an investigational use).
The data are being presented in oral sessions during the American Society for Reproductive Medicine (ASRM) 2021 Congress.
“These studies provide important new data for relugolix combination therapy, including detailed two-year efficacy and safety data in women with heavy menstrual bleeding associated with uterine fibroids from the Phase 3 LIBERTY studies,” said Juan Camilo Arjona Ferreira, M.D., Chief Medical Officer of Myovant Sciences, Inc.
“They also provide additional insight into the potential effect of relugolix combination therapy in women with pain associated with endometriosis.”
“These presentations also include the results of the first pooled analysis of data from the LIBERTY and SPIRIT studies, which strengthen our clinical understanding of relugolix combination therapy and its potential benefits for women with these common and often debilitating conditions,” said James Rusnak, M.D., Ph.D., Senior Vice President, Chief Development Officer, Internal Medicine and Hospital, Global Product Development at Pfizer.
Details of the presentations of data from the Phase 3 LIBERTY randomized withdrawal study of women with uterine fibroids are as follows:
- LIBERTY Randomized Withdrawal Study: 2-Year Efficacy and Safety of Relugolix Combination Therapy in Women with Heavy Menstrual Bleeding Associated with Uterine Fibroids (Scientific Congress Prize Paper)
This presentation reports on the results of the Phase 3 LIBERTY randomized withdrawal study, which was designed to evaluate the efficacy and safety of relugolix combination therapy for up to two years in premenopausal women with heavy menstrual bleeding associated with uterine fibroids who completed the 24-week LIBERTY 1 or 2 trials and the 28-week long-term extension study.
- Effects of Relugolix Combination Therapy on Bone Mineral Density through 2 Years in Women with Heavy Menstrual Bleeding Associated with Uterine Fibroids
This presentation shares data on changes in bone mineral density observed in the Phase 3 LIBERTY randomized withdrawal study, which reflects up to 104 weeks of treatment with relugolix combination therapy.
Details of the presentations of data from the SPIRIT 1 and 2 studies of women with pain associated with endometriosis are as follows:
- Relugolix Combination Therapy Improves Multiple Dimensions of Quality of Life in Women with Endometriosis-Associated Pain: Results from the SPIRIT Program
This presentation shares data on the potential effect of relugolix combination therapy on health-related quality of life domains, including emotional well-being, self-image and sense of control, which were assessed using the Endometriosis Health Profile (EHP)-30 questionnaire during the Phase 3 SPIRIT 1 and 2 studies.
Details of the presentations that assessed pooled data from both the LIBERTY and SPIRIT studies are as follows:
- Assessment of Common Adverse Events of Relugolix Combination Therapy in Premenopausal Women Treated for Symptomatic Estrogen-Driven Conditions: LIBERTY and SPIRIT Studies
This presentation shares data on the adverse events observed in premenopausal women on relugolix combination therapy, based on a pooled analysis of data from the LIBERTY 1/2 and SPIRIT 1/2 studies.
- Integrated Long-Term Bone Mineral Density (BMD) Outcomes in Women Receiving Relugolix Combination Therapy in LIBERTY and SPIRIT Studies vs. Non-Treated Women
This presentation reports on the results of a pooled assessment of data from the LIBERTY and SPIRIT studies and the LIBERTY long-term extension study, which analyzed bone mineral density outcomes in premenopausal women with uterine fibroids or endometriosis-associated pain.
In the U.S., relugolix combination tablet (relugolix 40 mg, estradiol 1.0 mg, and norethindrone acetate 0.5 mg) is currently available as MYFEMBREE® for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women, with a treatment duration of up to 24 months.
The U.S. Food and Drug Administration (FDA) approved MYFEMBREE for this indication on May 26, 2021, based on data from the Phase 3 LIBERTY program.
Myovant and Pfizer are jointly developing and commercializing MYFEMBREE in the U.S. Relugolix combination therapy is under investigation for the use of pain in endometriosis; the efficacy and safety for this use have not been demonstrated.
On September 9, 2021, Myovant and Pfizer announced that the FDA accepted for review a supplemental New Drug Application (sNDA) for MYFEMBREE for the management of moderate to severe pain associated with endometriosis with a target action date of May 6, 2022.
About MYFEMBREE®
MYFEMBREE (relugolix 40 mg, estradiol 1.0 mg, and norethindrone acetate 0.5 mg) is the first once-daily oral treatment for heavy menstrual bleeding associated with uterine fibroids in premenopausal women approved by the U.S. Food and Drug Administration, with a treatment duration of up to 24 months.
MYFEMBREE contains relugolix, which reduces the amount of estrogen (and other hormones) produced by ovaries, estradiol (an estrogen) which may reduce the risk of bone loss, and norethindrone acetate (a progestin) which is necessary when women with a uterus (womb) take estrogen.
For full prescribing information including Boxed Warning and patient information, please click here.
Indications and Usage
MYFEMBREE is indicated for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women. Limitations of Use: Use of MYFEMBREE should be limited to 24 months due to the risk of continued bone loss which may not be reversible.
Important Safety Information
BOXED WARNING: THROMBOEMBOLIC DISORDERS AND VASCULAR EVENTS
Estrogen and progestin combination products, including MYFEMBREE, increase the risk of thrombotic or thromboembolic disorders including pulmonary embolism, deep vein thrombosis, stroke and myocardial infarction, especially in women at increased risk for these events.
MYFEMBREE is contraindicated in women with current or a history of thrombotic or thromboembolic disorders and in women at increased risk for these events, including women over 35 years of age who smoke or women with uncontrolled hypertension.
CONTRAINDICATIONS
MYFEMBREE is contraindicated in women with any of the following: high risk of arterial, venous thrombotic, or thromboembolic disorder; pregnancy; known osteoporosis; current or history of breast cancer or other hormone-sensitive malignancies; known hepatic impairment or disease; undiagnosed abnormal uterine bleeding; known hypersensitivity to components of MYFEMBREE.
WARNINGS AND PRECAUTIONS
Thromboembolic Disorders: Discontinue immediately if an arterial or venous thrombotic, cardiovascular, or cerebrovascular event occurs or is suspected.
Discontinue at least 4 to 6 weeks before surgery associated with an increased risk of thromboembolism, or during periods of prolonged immobilization, if feasible.
Discontinue immediately if there is sudden unexplained partial or complete loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis as these have been reported with estrogens and progestins.
Bone Loss: MYFEMBREE may cause a decrease in bone mineral density (BMD) in some patients, which may be greater with increasing duration of use and may not be completely reversible after stopping treatment.
Consider the benefits and risks in patients with a history of low trauma fracture or risk factors for osteoporosis or bone loss, including medications that may decrease BMD.
Assessment of BMD by dual-energy X-ray absorptiometry (DXA) is recommended at baseline and periodically thereafter. Consider discontinuing MYFEMBREE if the risk of bone loss exceeds the potential benefit.
Hormone-Sensitive Malignancies: Discontinue MYFEMBREE if a hormone-sensitive malignancy is diagnosed. Surveillance measures in accordance with standard of care, such as breast examinations and mammography are recommended.
Use of estrogen alone or estrogen plus progestin has resulted in abnormal mammograms requiring further evaluation.
Depression, Mood Disorders, and Suicidal Ideation: Promptly evaluate patients with mood changes and depressive symptoms including shortly after initiating treatment, to determine whether the risks of continued therapy outweigh the benefits.
Patients with new or worsening depression, anxiety, or other mood changes should be referred to a mental health professional, as appropriate.
Advise patients to seek immediate medical attention for suicidal ideation and behavior and reevaluate the benefits and risks of continuing MYFEMBREE.
Hepatic Impairment and Transaminase Elevations: Steroid hormones may be poorly metabolized in these patients.
Instruct women to promptly seek medical attention for symptoms or signs that may reflect liver injury, such as jaundice or right upper abdominal pain.
Acute liver test abnormalities may necessitate the discontinuation of MYFEMBREE use until the liver tests return to normal and MYFEMBREE causation has been excluded.
Gallbladder Disease or History of Cholestatic Jaundice: Discontinue MYFEMBREE if signs or symptoms of gallbladder disease or jaundice occur.
For women with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, assess the risk-benefit of continuing therapy. Studies among estrogen users suggest a small increased relative risk of developing gallbladder disease.
Elevated Blood Pressure: For women with well-controlled hypertension, monitor blood pressure and stop MYFEMBREE if blood pressure rises significantly.
Change in Menstrual Bleeding Pattern and Reduced Ability to Recognize Pregnancy: Advise women to use non-hormonal contraception during treatment and for one week after discontinuing MYFEMBREE.
Avoid concomitant use of hormonal contraceptives. MYFEMBREE may delay the ability to recognize pregnancy because it alters menstrual bleeding. Perform testing if pregnancy is suspected and discontinue MYFEMBREE if pregnancy is confirmed.
Risk of Early Pregnancy Loss: MYFEMBREE can cause early pregnancy loss. Exclude pregnancy before initiating and advise women to use effective non-hormonal contraception.
Uterine Fibroid Prolapse or Expulsion: Advise women with known or suspected submucosal uterine fibroids about the possibility of uterine fibroid prolapse or expulsion and instruct them to contact their physician if severe bleeding and/or cramping occurs.
Alopecia: Alopecia, hair loss, and hair thinning were reported in phase 3 trials with MYFEMBREE. Consider discontinuing MYFEMBREE if hair loss becomes a concern. Whether the hair loss is reversible is unknown.
Effects on Carbohydrate and Lipid Metabolism: More frequent monitoring in MYFEMBREE-treated women with prediabetes and diabetes may be necessary. MYFEMBREE may decrease glucose tolerance and result in increased blood glucose concentrations.
Monitor lipid levels and consider discontinuing if hypercholesterolemia or hypertriglyceridemia worsens.
In women with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations in triglycerides levels leading to pancreatitis. Use of MYFEMBREE is associated with increases in total cholesterol and LDL-C.
Effect on Other Laboratory Results: Patients with hypothyroidism and hypoadrenalism may require higher doses of thyroid hormone or cortisol replacement therapy.
Use of estrogen and progestin combinations may raise serum concentrations of binding proteins (e.g., thyroid-binding globulin, corticosteroid-binding globulin), which may reduce free thyroid or corticosteroid hormone levels. Use of estrogen and progestin may also affect the levels of sex hormone-binding globulin, and coagulation factors.
Hypersensitivity Reactions: Immediately discontinue MYFEMBREE if a hypersensitivity reaction occurs.
ADVERSE REACTIONS
Most common adverse reactions for MYFEMBREE (incidence ≥3% and greater than placebo) were hot flush/hyperhidrosis/night sweats, abnormal uterine bleeding, alopecia, and decreased libido. These are not all the possible side effects of MYFEMBREE.
DRUG INTERACTIONS
P-gp Inhibitors: Avoid use of MYFEMBREE with oral P-gp inhibitors. If use is unavoidable, take MYFEMBREE first, separate dosing by at least 6 hours, and monitor patients for adverse reactions.
Combined P-gp and Strong CYP3A Inducers: Avoid use of MYFEMBREE with combined P-gp and strong CYP3A inducers.
LACTATION
Advise women not to breastfeed while taking MYFEMBREE.”
