Monthly News Roundup - September 2023
Medically reviewed by Drugs.com.
Subcutaneous Form of Entyvio Approved for Ulcerative Colitis
In addition to the intravenous (IV) formulation, the FDA has now approved subcutaneous (SC) Entyvio (vedolizumab) for maintenance therapy in adults with moderately-to-severely active ulcerative colitis (UC) after intravenous (IV) induction therapy with Entyvio. Patients or caregivers may inject Entyvio at home after training on the subcutaneous injection technique.
- Entyvio is an integrin receptor antagonist biologic for the treatment of moderately to severely active Crohn's disease and ulcerative colitis. It specifically targets circulating inflammatory white blood cells in the gut to help control inflammation and symptoms of ulcerative colitis and Crohn's disease.
- Approval of the SC formulation in UC was based on the Phase 3 VISIBLE 1 study that assessed safety and efficacy. After initial IV induction therapy, a statistically significant proportion of patients receiving Entyvio SC administered every 2 weeks achieved the primary endpoint of clinical remission (defined as a total Mayo score of ≤2 and no individual subscore >1) compared to patients receiving placebo (46% vs. 14%; p<0.001) at Week 52.
- Following the first two IV doses administered by a healthcare provider at Week 0 and Week 2 in UC, Entyvio may be switched to SC injection (given under the skin in the thigh, abdomen, or upper arm area) at Week 6. The recommended SC dosage in UC starting at Week 6 is 108 mg administered every 2 weeks. Patients already in clinical response or remission beyond Week 6 may also be switched from the IV infusion to SC injection.
- New SC dosage forms include a single-dose pre-filled pen and a single-dose prefilled syringe.
- Adverse reactions to the SC form are similar to those reported with IV Entyvio with the exception of injection site reactions (including injection site redness, rash, swelling, bruising and hematoma).
FDA Clears Jardiance for Use in Chronic Kidney Disease (CKD)
In September, the FDA cleared Jardiance (empagliflozin), from Boehringer Ingelheim and Eli Lilly, to reduce the risk of further worsening of kidney disease, end-stage kidney disease (ESKD), death due to cardiovascular disease, and hospitalization in adults with chronic kidney disease (CKD).
- This is the fourth approved use for Jardiance, a sodium glucose co-transporter-2 (SGLT2) inhibitor also used for cardiovascular risk reduction, heart failure, and to improve glycemic (blood sugar) control in type 2 diabetes.
- Approval was supported by the Phase 3 EMPA-KIDNEY study with over 6,600 patients. Jardiance, in addition to standard care, demonstrated a 28% relative risk reduction (HR=0.72; 95% CI 0.64 to 0.82; P<0.0001) compared with placebo, for the composite primary endpoint of kidney disease progression or cardiovascular death. A 14% relative risk reduction in first and recurrent hospitalization, a key secondary endpoint, was also seen vs. placebo (HR=0.86; 95% CI 0.78 to 0.95; p=0.0025).
- The recommended dose for this use is 10 mg orally once daily in the morning, taken with or without food.
- Jardiance is not recommended for the treatment of CKD in patients with polycystic kidney disease, or who are taking or have recently received certain types of immunosuppressive therapy to treat kidney disease, as it is not expected to work in these conditions.
- The most common side effects of Jardiance include urinary tract infections and yeast infections in females. Serious side effects include diabetic ketoacidosis, dehydration, low blood sugar, necrotizing fasciitis of the perineum, and lower limb amputations, among others.
Exxua Approved to Treat Major Depressive Disorder in Adults
In September, the FDA cleared Exxua (gepirone) extended-release tablets to treat Major Depressive Disorder (MDD) in adults. MDD is a debilitating disorder characterized by low mood, inability to feel pleasure, feelings of worthlessness, low energy, and other emotional and physical symptoms, including suicide in the most severe cases.
- Exxua, a novel azapirone antidepressant, is thought to work as a selective agonist at serotonin (5HT)1A receptors, modulating serotonergic activity in the central nervous system. This unique mechanism of action may allow for the relief of depression without significant side effects seen with other antidepressants, including sexual dysfunction and weight gain.
- The recommended starting dose is 18.2 mg administered orally once daily with food at approximately the same time each day. Depending on clinical response and tolerability, the dosage may be increased.
- The Exxua product label carries a Boxed Warning for the increased risk of suicidal thinking and behavior in pediatric and young adult patients taking antidepressants. Exxua is not approved for use in pediatric patients.
- Warnings and precautions associated with Exxua include QT interval prolongation, serotonin syndrome, and activation of mania/hypomania. Common adverse reactions include dizziness, nausea, insomnia, abdominal (stomach area) pain, and dyspepsia (heartburn).
- Exxua is manufactured by Fabre-Kramer Pharmaceuticals.
FDA Approves GSK’s Ojjaara for Myelofibrosis
This past month, the FDA approved Ojjaara (momelotinib) for the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (post-polycythemia vera and post-essential thrombocythemia), in adults with anemia. Ojjaara is a once-a-day, oral JAK1/JAK2 and activin A receptor type 1 (ACVR1) inhibitor.
- Myelofibrosis is a rare type of bone marrow cancer (blood cancer) that disrupts the body's normal production of blood cells and affects about 25,000 patients in the U.S.
- Ojjaara addresses the key manifestations of the disease, namely anemia (low blood counts), constitutional symptoms (like fatigue, night sweats, and bone pain), and splenomegaly (enlarged spleen).
- Approval was supported by data from the MOMENTUM and SIMPLIFY-1 Phase 3 studies. In the MOMENTUM trial, a statistically significant response with respect to constitutional symptoms, splenic response and transfusion independence was seen when momelotinib was compared to danazol. In SIMPLIFY-1, Ojjaara efficacy was based on spleen volume response (reduction by 35% or greater).
- The recommended dose of Ojjaara tablets is 200 mg orally once daily with or without food. In severe hepatic (liver) impairment, reduce the starting dose to 150 mg orally once daily.
- In studies, the most common adverse reactions were thrombocytopenia (low platelets), hemorrhage (bleeding), bacterial infection, fatigue, dizziness, diarrhea, and nausea. Serious warnings include risk of infections, thrombocytopenia, neutropenia (low white blood cells), and liver toxicity, among others.
Aphexda Hematopoietic Stem Cell Mobilizer Approved in Multiple Myeloma
In September, the FDA approved Aphexda (motixafortide) injection in combination with filgrastim (Neupogen, G-CSF), to be used in patients with multiple myeloma to help increase the number of circulating stem cells before collection for an autologous stem cell transplant.
- Multiple myeloma is a form of blood cancer that develops in plasma cells found in the bone marrow. Stem cell transplantation is part of the standard treatment for multiple myeloma and prolongs survival for patients.
- Aphexda, a CXCR4 antagonist, works by blocking the receptor CXCR4 which increases circulating stem cells for collection.
- Approval was based on the results from the Phase 3 GENESIS trial in 122 patients, comparing Aphexda + filgrastim to placebo + filgrastim. In the Aphexda + filgrastim group, 67.5% of patients achieved the stem cell collection goal of ≥ 6 × 106 CD34+ cells / kg within two apheresis (blood collection) sessions, versus 9.5% for the placebo + filgrastim regimen. In the Aphexda arm, 92.5% of patients reached the stem cell collection goal in up to two apheresis sessions vs. 21.4% in the placebo arm.
- Aphexda 1.25 mg/kg is given via subcutaneous injection 10 to 14 hours prior to initiation of apheresis. Initiate Aphexda treatment after filgrastim has been administered daily for 4 days.
- Warnings include anaphylactic shock and allergic reactions, among others. Premedicate the patient with an H1-antihistamine, H2 blocker, and a leukotriene inhibitor before each Aphexda dose.
- The most common adverse reactions (>20%) are injection site reactions (pain, redness, itching), itching in general, flushing, and back pain.
- Aphexda is manufactured by BioLineRx Ltd.
FDA Approves Pombiliti + Opfolda for Late-Onset Pompe Disease
Pompe disease, a rare and life-threatening lysosomal storage disease, is a genetic deficiency of the enzyme alpha-glucosidase (GAA). This deficiency causes a build-up of glycogen (a storage form of sugar) in the muscles, leading to muscle weakness and eventually affecting the ability of the person to move and breath. It affects about 1 in 40,000 people in the U.S.
- In response, the FDA has approved Pombiliti (cipaglucosidase alfa-atga) intravenous (IV) infusion + Opfolda (miglustat) 65 mg oral capsules to treat adults with late-onset Pompe disease (LOPD) weighing ≥40 kg (88 lbs) and not improving on their current enzyme replacement therapy (ERT).
- Pombiliti is a bis-M6P (Mannose 6-Phosphate)-enriched recombinant human GAA enzyme (rhGAA) that facilitates high-affinity uptake through the M6P receptor. Once in the cell, Pombiliti can be properly processed to break down glycogen. Opfolda is an oral enzyme stabilizer, used to help reduce loss of enzyme activity in the blood.
- Approval was supported by clinical data observed from the Phase 3 pivotal study PROPEL. Results showed clinically meaningful improvements in the key domains of Pompe disease (muscle strength, pulmonary and motor function, patient-reported outcomes and biomarkers) over standard of care, even among those who had been receiving approved therapy for at least 2 years.
- Pombiliti + Opfolda is given every 2 weeks. Treatment is started 2 weeks after the last ERT dose. The Pombiliti infusion is given by a healthcare provider and is started about 1 hour after taking the oral Opfolda dose. The recommended dose of Pombiliti is 20 mg/kg given every other week as an IV infusion over approximately 4 hours. Premedication is suggested. The recommended dose of Opfolda is: 260 mg for patients weighing ≥50 kg OR 195 mg for patients weighing ≥40 kg to <50 kg. Swallow Opfolda capsules whole only with unsweetened beverages (water, tea or coffee with no cream, sugar, or sweeteners). Do not drink other beverages or eat food for at least 2 hours before and 2 hours after taking Opfolda.
- Pombiliti carries a Boxed Warning for hypersensitivity reactions including anaphylaxis, infusion reactions and risk of acute cardiorespiratory failure in susceptible patients. Common side effects (≥ 5%) with the combined treatment are headache, diarrhea, fatigue, nausea, abdominal pain, and pyrexia (fever). May cause embryo-fetal harm. Verify pregnancy status in females of reproductive potential prior to initiating treatment.
- Pombilit + Opfolda is from Amicus Therapeutics and will be available immediately in the US.
Ryzumvi Eye Drops Soon Available to Reverse Pupil Dilation After Eye Exams
Dilation of pupils (mydriasis) with eye drops often occurs during eye exams, but can last up to 24 hours. Side effects like sensitivity to light (photophobia) and blurred vision may hinder return to reading, work and driving. Examples of drops that cause the pupil to dilate include phenylephrine (an adrenergic agonist) and tropicamide (a parasympatholytic agent).
- In September, the FDA cleared Ryzumvi (phentolamine mesylate) ophthalmic solution) 0.75% for patients 3 years of age and older to reverse pharmacologically-induced mydriasis (pupil dilation) produced by adrenergic agonists or parasympatholytic agents.
- Ryzumvi, an alpha adrenergic blocker, reverses pharmacologically-induced mydriasis by blocking the α1 receptors on the iris dilator muscle to reduce pupil size.
- In the MIRA-2 study, Ryzumvi started to return pupil size to normal starting one hour after use. By 3 hours, 80% of patients in the Ryzumvi group had their pupils return to normal size, compared to 18% of patients who had not used Ryzumvi eye drops. Ryzumvi is administered into each dilated eye following the completion of the ophthalmic examination or procedure to reverse pupil dilation.
- The most common adverse reactions are instillation site discomfort (16%), conjunctival hyperemia/eye redness (12%), and dysgeusia/altered taste (6%). It is not recommended to be used in patients with active eye inflammation.
- Ryzumvi is expected to be commercially available in the U.S. in the first half of 2024. It is manufactured by Ocuphire Pharma / Viatris.
Posted September 2023
More news resources
- FDA Medwatch Drug Alerts
- Daily MedNews
- News for Health Professionals
- New Drug Approvals
- New Drug Applications
- Drug Shortages
- Clinical Trial Results
- Generic Drug Approvals
Subscribe to our newsletter
Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.