Monthly News Roundup - July 2024
Lilly’s Kisunla Approved to Treat Early Symptomatic Alzheimer's Disease
In July, the FDA cleared Eli Lilly’s Kisunla (donanemab-azbt), an amyloid beta-directed monoclonal antibody indicated for the treatment of early symptomatic Alzheimer’s disease. Kisunla is given as a once-monthly IV infusion. Treatment with Kisunla should be initiated in patients with mild cognitive impairment (MCI) or mild dementia stage of disease, the population in which treatment was initiated in studies.
- Amyloid is a protein produced naturally in the body that can clump together to create plaques in the brain that may lead to memory and thinking issues associated with Alzheimer's disease.
- Donanemab-azbt is a humanized IgG1 antibody that targets a modified form of beta amyloid plaque called N3pG. Kisunla is thought to work by helping the body remove the excessive buildup of amyloid plaques in the brain.
- FDA approval was based on the 18 month, Phase 3, placebo-controlled TRAILBLAZER-ALZ 2 study (N = 1736) in those with less advanced disease (low to medium tau protein levels) or the overall combined population (low/medium + high tau protein levels). Patients were assessed using the Integrated Alzheimer’s Disease Rating Scale (iADRS), which measures memory, thinking, and daily functioning.
- Treatment with Kisunla significantly slowed clinical decline in both groups compared to placebo. People with the least advanced disease experienced the strongest outcomes, with a 35% slowing of decline on the iADRS score. The overall population had a 22% slowing on the iADRS score, with both groups having up to a 39% lower risk of progressing to the next clinical stage of disease.
- In addition, in the overall population Kisunla reduced amyloid plaques on average by 61% at 6 months, 80% at 12 months, and 84% at 18 months compared to the start of the study via positron emission tomography (PET). Dosing was continued or stopped in response to observed effects on amyloid imaging. The percentages of patients eligible for a switch to placebo based on amyloid PET levels at Week 24, Week 52, and Week 76 timepoints were 17%, 47%, and 69%, respectively.
- Kisunla is administered as a 700 mg intravenous (IV) infusion over approximately 30 minutes every 4 weeks for the first 3 doses, followed by 1,400 mg every 4 weeks. Confirm the presence of amyloid beta pathology prior to initiating treatment.
- The Kisunla label carries a Boxed Warning for amyloid-related imaging abnormalities (ARIA), such as edema (ARIA-E), microhemorrhage (ARIA-H microhemorrhage) and superficial siderosis (ARIA-H superficial siderosis). Use caution with use of antithrombotic drugs or in patients who are ApoE ε4 homozygotes. ARIA is usually asymptomatic, although serious, life-threatening and fatal events can rarely occur. Warnings and precautions also include injection-site reactions.
- The most commonly reported adverse events were ARIA-E (24% vs. 2% placebo), ARIA-H microhemorrhage (25% vs. 11% placebo), ARIA-H superficial siderosis (15% vs. 3% placebo), headache (13% vs. 10% placebo), and infusion-related reaction (9% vs. 0.5% placebo).
FDA Approves Oral Zunveyl for the Treatment of Alzheimer's Disease
Alpha Cognition has received approval for Zunveyl (benzgalantamine) delayed-release oral tablet formulation for the treatment of mild-to-moderate Alzheimer’s disease in adults. Benzgalantamine is a prodrug of the active metabolite galantamine, an acetylcholinesterase inhibitor.
- Galantamine (brand name: Razadyne, Razadyne ER) has been previously approved as an oral treatment for Alzheimer’s disease (AD).
- AD slowly destroys memory, thinking skills, and eventually the ability to do tasks like engaging in conversation and self-care. Zunveyl is thought to work by increasing levels of acetylcholine in the brain.
- Zunveyl tablets are administered orally twice daily with or without food. Its delayed-release formulation is designed with an enteric coating to help lower stomach side effects.
- The efficacy of Zunveyl is based upon 3 bioavailability studies in healthy adults comparing galantamine immediate-release tablets and galantamine extended-release capsules to Zunveyl. Stomach-related side effects documented across all studies for Zunveyl were less than 2% and no insomnia (trouble sleeping) was observed.
- Warnings and precautions associated with Zunveyl include serious skin reactions, increased risk for adverse effects on cardiac conduction, gastrointestinal bleeding, bladder outflow obstruction, and respiratory adverse events in patients with a history of severe asthma or obstructive pulmonary disease.
- Common adverse reactions are similar to galantamine and include nausea, vomiting, diarrhea, dizziness, headache, and decreased appetite.
Genentech’s Vabysmo Prefilled Syringe (PFS) Approved for Retinal Eye Diseases
In July the FDA approved a 6 mg single-dose prefilled syringe (PFS) of Vabysmo (faricimab-svoa) for intravitreal (injection into the eye) to treat wet, or neovascular, age-related macular degeneration (AMD), diabetic macular edema (DME) and macular edema following retinal vein occlusion (RVO). Vabysmo PFS delivers the same medicine found in the Vabysmo vials.
- AMD, DME and RVO are three retinal eye diseases that affect close to 3 million people in the U.S. and can lead to vision loss.
- Vabysmo is a bispecific antibody that blocks two signaling pathways: angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A). Vabysmo is thought to stabilize blood vessel leaking and inflammation that may contribute to retinal eye disease and vision loss.
- Vabysmo is administered by a healthcare provider and is usually given initially every 4 weeks for the first 4 to 6 doses and then as advised by your doctor.
- Do not use this product in patients who have an infection in or around their eye, have active swelling around their eye that may include pain and redness, or are allergic to Vabysmo or any ingredients.
- Warnings and precautions include endophthalmitis (eye infection) and retinal detachments (separation of layers of the retina), increases in intraocular pressure (increase in pressure in the eye) and risk of arterial thromboembolic events (blood clots, such as non-fatal heart attacks or strokes, and vascular death).
- The most common adverse reactions (≥5%) reported in patients receiving Vabysmo were cataract (15%) and blood on the white of the eye (conjunctival hemorrhage, 8%).
Zoryve Topical Cream OK’d for the Treatment of Atopic Dermatitis
This past month, the FDA cleared lower strength Zoryve (roflumilast) cream, 0.15%, indicated for the treatment of mild to moderate atopic dermatitis (AD) in adults and children 6 years of age and older. Zoryve is a once-daily, steroid-free cream used for long-term disease control.
- AD is the most common form of eczema, affecting over 9 million children and 16 million adults in the U.S. Itching (pruritus) is the most burdensome symptom of AD.
- Zoryve acts as a topical phosphodiesterase 4 (PDE4) inhibitor. PDE4 is an intracellular enzyme that increases the production of pro-inflammatory mediators and decreases production of anti-inflammatory mediators.
- The 0.15% cream is applied once daily to areas with mild to moderate atopic dermatitis
- In the Phase 3 INTEGUMENT-1 and INTEGUMENT-2 clinical trials, Zoryve cream 0.15% showed significant skin clearance as well as significant and sustained reduction in itch as soon as 24 hours following the first application. It is supplied in a 60-gram tube of 1.5 mg of roflumilast per gram.
- Common side effects for atopic dermatitis include headache (2.9%), nausea (1.9%), application site pain (1.5%), diarrhea (1.5%), and vomiting (1.5%).
- Zoryve is also approved to treat plaque psoriasis (using the 0.3% cream) and seborrheic dermatitis (using the 0.3% foam). It is manufactured by Arcutis.
FDA Clears Sun Pharma’s Leqselvi for the Treatment of Severe Alopecia Areata
Sun Pharma has announced approval of Leqselvi (deuruxolitinib) 8 mg tablets for the treatment of adults with severe alopecia areata.
- Alopecia areata is an autoimmune disease in which the immune system attacks hair follicles, resulting in partial or complete loss of hair on the scalp, face and body. Alopecia areata can be associated with serious psychological consequences, including anxiety and depression.
- Leqselvi contains deuruxolitinib, a JAK1/JAK2 inhibitor that works in the treatment of alopecia areata by targeting the γc cytokine and interferon-gamma (IFN-γ) signaling pathway to reverse hair loss.
- Approval was based on the 24-week Phase 3 THRIVE-AA1 and THRIVE-AA2 studies in 1,223 patients ages 18 to 65 with at least a 6 month history of alopecia areata with at least 50% scalp hair loss as measured by Severity of Alopecia Tool (SALT). The primary endpoint was met, with more than 30% of patients taking Leqselvi experiencing 80% or more scalp hair coverage (SALT ≤20) vs. placebo. Up to 25% of patients had almost all of their scalp hair back at 24 weeks (≥90% coverage).
- The recommended dose of Leqselvi is 8 mg orally twice daily. It is contraindicated (not used) in patients who are CYP2C9 poor metabolizers or who are using moderate or strong CYP2C9 inhibitors.
- Labeling includes a Boxed Warning for serious infections, death, malignancy (cancer), major adverse cardiovascular (heart-related) events (MACE) such as heart attack, stroke or death, and thrombosis (clot formation).
- The most common adverse reactions (≥1%) include headache, acne, nasopharyngitis (common cold symptoms), increased blood creatine phosphokinase, hyperlipidemia (high blood lipids like cholesterol), fatigue, and weight gain, among others.
FDA Approves Femlyv, the First Orally Disintegrating Birth Control Pill
Femlyv (ethinyl estradiol and norethindrone acetate) was approved in July as the first orally-disintegrating combination oral contraceptive (COC) for use by females of reproductive potential to prevent pregnancy. Femlyv is designed for individuals who have trouble swallowing their medication.
- Norethindrone acetate (a progestin) and ethinyl estradiol (an estrogen) have been approved in the U.S. as an oral, swallowable birth control pill since 1968.
- Femlyv is taken by placing one orally disintegrating tablet (ODT) on the tongue, allowing it to dissolve, and then following with 8 ounces. (240 mL) of water. Each blister card contains 24 ODTs with 1 mg norethindrone acetate and 0.02 mg ethinyl estradiol per tablet and 4 inert ODTs.
- The efficacy in females of reproductive potential with a body mass index (BMI) of more than 35 kg/m2 has not been evaluated
- Femlyv may lead to contraceptive failure and/or increase breakthrough bleeding with CYP3A inducers. Avoid concomitant use, or use a back-up method or alternative method of contraception during co-administration and up to 28 days after discontinuation of the CYP3A inducer.
- Boxed warnings include cigarette smoking and serious cardiovascular events from COC use. Women over 35 years old who smoke should not use Femlyv. Other warnings are blood clotting disorders, high blood pressure, migraine, hormonally-sensitive malignancy, glucose tolerance and hypertriglyceridemia, gallbladder disease and cholestasis, and uterine bleeding.
- The most common adverse reactions (≥2%) include headache (6.3%), vaginal yeast infection (6.1%), nausea (4.6%), menstrual cramps (4.4%) and breast tenderness (3.4%) among others.
- Femlyv is manufactured by Millicent Puerto Rico.
FDA Approves Erzofri to Treat Schizophrenia and Schizoaffective Disorder
Luye Pharma has announced approval of Erzofri (paliperidone palmitate) extended-release injectable suspension, an atypical antipsychotic used to treat schizophrenia and schizoaffective disorder in adults.
- Erzofri is metabolized to paliperidone, which is the primary active metabolite of risperidone. Paliperidone is thought to work in treating schizophrenia by blocking dopamine (D2) and serotonin (5-HT2A) receptors in the brain.
- Schizophrenia makes it difficult for a person to tell the difference between real and unreal experiences, to think logically or have normal emotional responses or behaviors. Patient adherence to antipsychotics is generally poor, but using long-acting injectable antipsychotics like Erzofri may improve compliance.
- Erzofri is injected once per month by a healthcare provider. For patients who have not used injected/oral paliperidone or risperidone, establish tolerability first with oral agents.
- Erzofri carries a Boxed Warning for increased risk of death in elderly patients with dementia-related psychosis. It is not approved for use in patients with dementia-related psychosis.
- Warnings and precautions also include stroke, transient ischemic attack, (including fatalities) in elderly with dementia-related psychosis, neuroleptic malignant syndrome, QT Prolongation (abnormal heart rhythm), and tardive dyskinesia (movement disorder), among several others.
- Common side effects can include: injection site reactions, feeling tired or drowsy, dizziness, akathisia (feeling of restlessness), and extrapyramidal disorder (movement disorders).
Epysqli is Now the Second Biosimilar to Soliris
In July the FDA approved Epysqli (eculizumab-aagh), a complement inhibitor biosimilar to Soliris (eculizumab) from Samsung Bioepis Co. Epysqli is indicated for the treatment of paroxysmal nocturnal hemoglobinuria in adults and atypical hemolytic uremic syndrome in adult and pediatric patients. Epysqli is not approved to treat hemolytic uremic syndrome due to Shiga toxin E. coli (STEC-HUS).
- Epysqli is the second FDA-approved Soliris biosimilar, following the approval of Bkemv (eculizumab-aeeb) in May 2024. Unlike Bkemv, Epysqli does not have an interchangeability designation with Soliris.
- Epysqli is administered by intravenous (IV) infusion over 35 minutes in adults and 1 to 4 hours in pediatric patients.
- Biosimilar drugs must meet the same standards for pharmaceutical quality, safety and efficacy as reference products.
- Epysqli comes with a Boxed Warning for serious meningococcal infections, is available only through a restricted program called Epysqli REMS due to this risk, and is contraindicated in patients with unresolved serious Neisseria meningitidis infection.
- Warnings and precautions include use in patients with any other systemic infection and potential infusion-related reactions.
- Common adverse reactions may include headache, diarrhea, nasopharyngitis (common cold symptoms), back pain, and nausea/vomiting among others, and depending upon use.
FDA Approves Once Daily Zituvimet XR for Adults with Type 2 Diabetes
The extended-release form of Zituvimet, known as Zituvimet XR (sitagliptin and metformin hydrochloride extended-release tablet) is now approved as an adjunct to diet and exercise to improve blood sugar control in adults with type 2 diabetes. New extended-release strengths include 50 / 500, 50 / 1000 and 100 / 1000 sitagliptin / metformin tablets.
- Zituvimet is a biguanide and dipeptidyl peptidase-4 (DPP-4) inhibitor combination also available in an regular-release dosage form (50 mg sitagliptin / 500 mg metformin or 50 mg sitagliptin / 1,000 mg metformin).
- The metformin and sitagliptin combination was first approved in 2007 as Janumet. The Janumet XR extended release formulation was approved in 2012.
- Zituvimet XR tablets are taken orally once daily with a meal, while the earlier approved regular-release form of Zituvimet is taken twice daily with meals.
- The label carries a Boxed Warning for an increased risk of metformin-associated lactic acidosis (a rare but serious condition of buildup of an acid in the blood) that can cause death. Lactic acidosis is a medical emergency and must be treated in the hospital.
- Warnings and precautions include pancreatitis, heart failure, acute renal failure, vitamin B12 deficiency, an increased risk of low blood sugar (hypoglycemia) when used in combination with insulin and/or an insulin secretagogue, among others.
- Common adverse reactions include diarrhea, upper respiratory tract infection, and headache.
- Zituvimet XR is manufactured by Zydus Lifesciences.
Posted July 2024
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.