Monthly News Roundup - May 2023
Medically reviewed by Drugs.com.
FDA Approves Once-Daily SGLT Inhibitor Inpefa to Treat Heart Failure
Over 6 million Americans suffer from heart failure, with the prevalence expected to rise to 8 million by 2030. In response, the US Food and Drug Administration (FDA) has given the thumbs up to Lexicon’s Inpefa (sotagliflozin), a once-daily oral tablet to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors.
- The indications include a broad range for left ventricular ejection fraction (LVEF), including preserved ejection fraction and reduced ejection fraction, and for patients with or without diabetes.
- Inpefa is both a sodium-glucose co-transporter type 2 (SGLT2) and type 1 (SGLT1) inhibitor. SGLT2 is responsible for glucose reabsorption by the kidney and SGLT1 is responsible for glucose absorption in the gastrointestinal tract.
- This class is recommended in guidelines as a first-line treatment for the management of heart failure from the American Heart Association (AHA), the American College of Cardiology (ACC), and the Heart Failure Society of America (HFSA).
- Approval was based on two Phase 3 studies in about 12,000 patients. Results showed that Inpefa significantly reduced risk of the composite of hospitalizations for heart failure, urgent visits for heart failure, and cardiovascular death by 33% compared to placebo in patients who had been recently hospitalized for worsening heart failure.
- Warnings include increased risk of ketoacidosis (high ketones which can make blood acidic), volume depletion, genital mycotic (fungal) infections and serious urinary tract infections, among others. The most commonly reported adverse reactions (incidence ≥ 5%) were urinary tract infection, volume depletion, diarrhea, and hypoglycemia (low blood sugar).
- Inpefa is expected to be commercially available by the end of June 2023.
Rexulti Label Expanded for Agitation Associated with Dementia Due to Alzheimer’s Disease
This past month, the FDA approved Rexulti (brexpiprazole) for use in the treatment of agitation associated with dementia due to Alzheimer’s disease. It is not indicated for as needed (“prn”) treatment for agitation associated with dementia due to Alzheimer’s disease and is not approved to treat patients with dementia-related psychosis without agitation associated with dementia due to Alzheimer’s disease.
- Rexulti, from Otsuka / Lundbeck, is an oral atypical antipsychotic also approved for use in the treatment of major depressive disorder (MDD) and schizophrenia. It works by adjusting the imbalance of natural chemicals (called neurotransmitters) in the brain, such as dopamine and serotonin, to help lower symptoms of these diseases.
- Agitation associated with dementia due to Alzheimer’s disease is a common neuropsychiatric symptom in Alzheimer’s dementia, can be stressful caregivers and may lead to early nursing home placement. A person with agitation of Alzheimer's dementia may feel irritable, restless, make repetitive movements, walk up and down, or try to leave the house. Other behavioral symptoms may include profanity, shouting, shoving, and hitting.
- In two 12-week long, placebo-controlled studies, patients receiving the Rexulti 2 mg/day or 3 mg/day dose achieved a 31% greater reduction from baseline in frequency of agitation symptoms vs. placebo. The 1 mg/day dose did not demonstrate significantly greater mean changes at baseline from the placebo group and this dose is not approved as a maintenance dose.
- The starting dose for this indication is 0.5 mg taken once daily on Days 1 to 7; then 1 mg once daily on Days 8 through 14; on Day 15 increase to 2 mg once daily (the target dose).
- Rexulti still carries a Boxed Warning for the treatment of patients with dementia-related psychosis without agitation associated with dementia due to Alzheimer’s disease. The most common side effects of Rexulti (≥4%) for this use include: nasopharyngitis (common cold symptoms) and dizziness. Other common side effects include: weight gain, sleepiness and restlessness or feeling like you need to move (akathisia).
AbbVie’s Rinvoq is First Daily Pill Approved to Treat Crohn’s Disease
In May, the FDA approved Rinvoq (upadacitinib) for the treatment of adults with moderately to severely active Crohn's disease who have had an inadequate response or intolerance to one or more TNF blockers. Rinvoq is a Janus kinase (JAK) inhibitor also approved to treat rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis.
- Approval was supported by data from two induction studies, U-EXCEED and U-EXCEL, as well as the U-ENDURE maintenance study. The co-primary endpoints and key secondary endpoints with Rinvoq were achieved when compared to placebo. In U-EXCEED and U-EXCEL, the co-primary endpoints were the proportion of patients achieving clinical remission (by CDAI) at Week 12, and the proportion of patients achieving endoscopic response (by SES-CD) at Week 12. In the U-ENDURE study, the co-primary endpoints of clinical remission (by CDAI) and endoscopic response (by SESCD) were assessed at Week 52.
- Rinvoq extended-release tablets are administered orally once daily. The recommended induction dosage for Rinvoq for this use is 45 mg once daily for 12 weeks. The recommended maintenance dosage is 15 mg once daily.
- Rinvoq carries a boxed warning for the risk of serious infections, an increased rate of all-cause mortality, malignancies, adverse cardiovascular events (MACE), and thrombosis.
- In Crohn’s disease studies, the most common side effects were upper respiratory tract infections, anemia (low red blood cells), pyrexia (fever), acne, herpes zoster (shingles), and headache.
Epkinly Gains Accelerated Approval for Diffuse Large B-Cell Lymphoma (DLBCL)
The FDA has cleared Epkinly (epcoritamab-bysp), AbbVie’s bispecific CD20-directed CD3 T-cell engager, as a treatment for adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), after two or more lines of systemic therapy. Epkinly was approved under the FDA's Accelerated Approval program based on response rate and durability of response. Continued approval for this use may be dependent upon additional studies.
- DLBCL is a type of aggressive, fast-growing non-Hodgkin's lymphoma (NHL), a blood cancer that develops in the lymphatic system and affects B cells, a type of white blood cell. It is the most common type of NHL.
- Epkinly works by binding to the CD3 receptor expressed on the surface of T-cells and CD20 expressed on the surface of lymphoma cells and healthy B-lineage cells. It induces T-cell mediated killing of CD20+ cells.
- In the EPCORE NHL-1 trial, Epkinly delivered an overall response rate of 61%, a complete response rate of 38% and median duration of response of 15.6 months in heavily pretreated R/R DLBCL patients.
- Epkinly is available as an off-the-shelf vial and given as an injection under the skin (subcutaneous injection) by a healthcare provider. It’s typically given in cycles that are usually 28 days long, and given every week during Cycles 1 to 3, every 2 weeks during Cycles 4 to 9, and every 4 weeks starting with Cycle 10.
- Epkinly carries a Boxed Warning for serious or life-threatening cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Warnings and precautions include infections, cytopenias (low blood cells), and the risk of harm to an unborn baby.
- The most common (≥ 20%) adverse reactions were cytokine release syndrome, fatigue, musculoskeletal pain, injection site reactions, pyrexia (fever), abdominal (stomach area) pain, nausea, and diarrhea.
Opvee Nasal Spray Cleared to Reverse Opioid Overdose
In May, the FDA approved Opiant Pharmaceuticals’ Opvee (nalmefene hydrochloride), a nasal spray formulation for use in the treatment of opioid overdose induced by natural or synthetic opioids in people 12 years of age and older with signs of breathing problems and severe sleepiness or not being able to respond. Opvee provides fast onset and long duration reversal of opioid-induced respiratory depression.
- Nalmefene is an opioid antagonist approved in 1995. Opioid antagonists work by blocking opioid receptors found in the brain to reverse respiratory depression, sedation, and hypotension.
- Opvee nasal spray is given as a single spray into the nose and does not take the place of emergency medical care. Additional doses may be administered, if needed, until emergency medical assistance arrives.
- In studies, Opvee had an onset of action of 2.5 to 5 minutes and fully reversed respiratory depression as early as 5 minutes. While the duration of action of nalmefene is as long as most opioids, a recurrence of respiratory depression is still possible.
- Opvee may cause serious side effects, including sudden opioid withdrawal symptoms or risk of opioid overdose in someone who tries to overcome its opioid-blocking effects.
- Common side effects include nasal discomfort or pain, vomiting, headache, anxiety, decreased appetite, nausea, tiredness, dizziness, nasal congestion, taste changes, hot flush, skin redness and increased sweating.
- Opvee is expected to be on the market in the 4th quarter of 2023.
Yuflyma is FDA-Approved as the Ninth Biosimilar to Humira
The FDA has approved Celltrion’s Yuflyma (adalimumab-aaty), a tumor necrosis factor (TNF) blocker biosimilar to Humira, now approved for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis, and hidradenitis suppurativa. It does not carry the uveitis indication like Humira (the reference product), and is not currently interchangeable at the pharmacy level.
- Yuflyma comes as a citrate-free and high-concentration (100mg/mL) product and is available as a pre-filled syringe and autoinjector option for subcutaneous injection.
- The approval of Yuflyma was based on clinical data showing that Yuflyma is comparable to the reference product in terms of efficacy, safety, pharmacokinetics, and immunogenicity up to 24 weeks and one year following treatment.
- Warnings include a risk of: serious infections, invasive fungal infections, cancer, serious allergies, and hepatitis B reactivation, among others. The most common adverse reactions (>10%) are: infections (e.g., upper respiratory, sinusitis), injection site reactions, headache and rash.
- Yuflyma is the ninth FDA-approved Humira biosimilar, and includes the recent approvals of Idacio (adalimumab-aacf) in 2022, Yusimry (adalimumab-aqvh) in 2022, Hulio (adalimumab-fkjp) in 2020, and Abrilada (adalimumab-afzb) in 2019.
- Yuflyma will be commercially available starting July 2023. Celltrion is also seeking an interchangeability designation from the FDA for Yuflyma, which is tentatively expected Q4 2024.
FDA Approves Xacduro for the Treatment of Serious Infections Caused by Acinetobacter
Xacduro is now FDA-approved for the treatment of adults with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex (Acinetobacter).
- Acinetobacter bacteria predominantly cause infections in critically ill hospitalized patients, often resulting in severe pneumonia and bloodstream infections.
- Xacduro, from Innoviva, is a co-packaged product containing the beta-lactam antibacterial sulbactam, and the beta-lactamase inhibitor durlobactam.
- Approval was based in-part on the Phase 3 ATTACK trial evaluating Xacduro versus colistin. In the trial, Xacduro demonstrated statistical non-inferiority (was not shown worse than) colistin for the primary endpoint of 28-day all-cause mortality in patients with carbapenem-resistant Acinetobacter infections and a significant difference in clinical cure rates.
- Xacduro is given every 6 hours by intravenous (IV) infusion over 3 hours in patients with creatinine clearance (CrCl) of 45 to 129 mL/min. Dosing adjustments are recommended for CrCl less than 45 mL/min and CrCl greater than or equal to 130 mL/min.
- Warnings and precautions associated with Xacduro include serious hypersensitivity (allergic) reactions and Clostridioides difficile-associated diarrhea (C. diff). In studies, the most common side effects (>10%) were liver test abnormalities, diarrhea, anemia, and hypokalemia (low potassium levels).
- Xacduro is expected to be available to clinicians and patients later in 2023.
Miebo Approved as First Agent to Reduce Tear Evaporation in Dry Eye Disease
In May, Bausch + Lomb and Novaliq GmbH announced the approval of Miebo (perfluorohexyloctane ophthalmic solution), a preservative-free, semifluorinated alkane eye drop indicated for treatment of signs/symptoms of dry eye disease (DED). Miebo is the first FDA-approved treatment for DED that directly reduces tear evaporation at the ocular surface.
- DED affects millions of Americans and is one of the most common ocular surface disorders. It is often associated with Meibomian Gland Dysfunction (MGD), where eyelid glands that normally secret oils to prevent tear evaporation are blocked or clogged, which can lead to dry eye syndrome.
- In the GOBI and MOJAVE phase 3 clinical trials in more than 1,200 patients with a history of DED and clinical signs of Meibomian gland dysfunction (MGD), Miebo met both primary sign and symptom efficacy endpoints (change from baseline at week eight (day 57 ± 2) in total corneal fluorescein staining (tCFS) and eye dryness Visual Analog Scale (VAS) score). Patients experienced relief of symptoms as early as day 15 and through day 57.
- The dose is one drop of Miebo four times daily into each eye. The most common adverse reactions experienced with Miebo were blurred vision (1.3% to 3%) and eye redness (1% to 3%).
- Miebo is expected to be commercially available in the second half of 2023.
FDA Approves Veozah for the Treatment of Vasomotor Symptoms Due to Menopause
Veozah (fezolinetant), from Astellas, is a newly approved selective neurokinin 3 (NK3) receptor antagonist indicated for the treatment of moderate to severe vasomotor symptoms (VMS) (hot flashes and/or night sweats) associated with menopause. Veozah is the first nonhormonal neurokinin 3 (NK3) receptor antagonist approved to treat VMS due to menopause.
- Vasomotor symptoms (VMS) are experienced by 60% to 80% of women and are the most common symptoms of menopause for which women seek treatment.
- Veozah works by helping to restore the balance between estrogens and neurokinin B (NKB), a brain chemical. Veozah blocks NKB in the temperature control center to reduce the number and intensity of hot flashes.
- Researchers from the SKYLIGHT 1 and SKYLIGHT 2 placebo-controlled clinical trials evaluated the co-primary efficacy endpoints in 1,022 women of change from baseline in moderate to severe vasomotor symptoms frequency and severity to Weeks 4 and 12. Results showed a significant reduction in frequency (≥ 2 hot flashes reduction over 24 hours from baseline) and a significant reduction in severity (over 24 hours) of moderate to severe vasomotor symptoms.
- The labeled dose is one 45 mg tablet orally once daily with or without food. Blood work to assess liver function is required before and during treatment.
- The most common side effects are abdominal (stomach area) pain, diarrhea, insomnia (trouble with sleep), back pain, hot flush, and liver enzyme elevation.
Posted May 2023
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