Zituvimet XR Approved for Diabetes
On July 18, 2024, Zydus Lifesciences was granted approval for Zituvimet™ XR tablets by the U.S. Food and Drug Administration (FDA). It is an extended-release formulation of a combination containing 50mg or 100mg of sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and 500mg or 1,000mg of metformin, a biguanide. It is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). The maximum recommended daily dose is 100mg of sitagliptin and 2,000 mg of metformin taken once daily with a meal. DPP-4 inhibitors should not be used to treat type 1 diabetes or patients who have a history of pancreatitis. All drugs that contain metformin have a boxed warning that taking them may increase the risk of lactic acidosis, a rare but potentially dangerous accumulation of acids in the body. According to IQVIA, annual U.S. sales of DPP-IV inhibitors and their combinations could reach $9.5 billion. Click here for the prescribing information.
Second Soliris Biosimilar, Epysqli, Approved, but Not Launched
On July 19, 2024, Samsung Bioepis received FDA approval for Epysqli® (eculizumab-aagh), the second biosimilar for Soliris® (eculizumab – Alexion/AstraZeneca). It is a monoclonal antibody that blocks the activity of complement C5, an immune system protein. Epysqli is approved to treat the rare inherited conditions paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). There are approximately 5,500 people in the U.S. with PNH and 600 with aHUS. Epysqli is given as an intravenous (IV) infusion. After loading doses, maintenance doses are administered once every two weeks – for adults at 900mg to treat PNH and 1,200mg for aHUS. Doses for pediatric patients depend on their weight. Amgen’s Bkemv™ (eculizumab-aeeb) was the first biosimilar for Soliris approved on May 28, 2024. It was granted interchangeable status and will be launched in March 2025. Epysqli is not deemed interchangeable with Soliris; the launch date is currently unknown. Similar to Soliris and Bkemv, Epysqli has a boxed warning and will be dispensed under a Risk Evaluation and Mitigation Strategy (REMS) due to the increased chance that patients using it may be more prone to acquiring meningitis that can be fatal. Full prescribing information can be found here.
Pediatric Indication Extended for Livmarli
Livmarli® (maralixibat – Mirum Pharmaceuticals) oral solution was approved to treat cholestatic pruritus in younger children with progressive familial intrahepatic cholestasis (PFIC) on July 24, 2024. Livmarli is an ileal bile acid transporter (IBAT) inhibitor that was originally approved in September 2021 to treat cholestatic pruritus caused by Alagille syndrome (ALGS). It received expanded approval in March 2024 to treat cholestatic pruritus in children five years of age and older with PFIC. Now, Livmarli is approved for children down to 12 months of age. The FDA also approved a higher concentration of Livmarli. The new 19mg/mL oral solution formulation should be used to treat PFIC. After an initial titration, the recommended dose for PFIC is 570mcg/kg twice daily. The 9.5mg/mL oral solution formulation should be used to treat ALGS. After an initial titration, the recommended dose for ALGS is 380mcg/kg once daily. Here is the revised labeling.
FDA Approves First Orally Disintegrating Contraceptive, Femlyv
Femlyv™ (norethindrone acetate/ethinyl estradiol) orally disintegrating tablets (ODT) received approval from the FDA on July 25, 2024. It is the first ODT formulation of an oral contraceptive. One tablet should be placed on the tongue and allowed to dissolve, followed by drinking 240mL of water once daily at the same time. The tablets should be taken in sequence as indicated on the blister pack. As with all OCs that contain progestin and estrogen, it has a boxed warning that the chance of adverse cardiovascular (CV) events is elevated for women, particularly those who are over the age of 35, who take an OC and also smoke cigarettes. It should also be used with caution due to risks such as venous thrombotic diseases and breast cancer. Femlyv is dispensed in 28-day blister packs of 24 tablets that contain the active ingredients and four inert tablets. Check here for its complete prescribing information.
Brineura Gets Expanded Indication
The FDA approved an expanded indication for Biomarin’s Brineura® (cerliponase alfa) on July 24, 2024. The enzyme replacement therapy is now indicated to slow the loss of ambulation (ability to walk or crawl) in pre-symptomatic or symptomatic pediatric patients of all ages with a rare form of Batten disease, called late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase 1 (TPP1) deficiency. Previously, its use was limited to pediatric patients three years of age and older who showed symptoms. CLN2 disease symptoms typically start as seizures in pediatric children between two years to four years of age. As the disease progresses, children experience delays in language development and lose the ability to walk and talk within a few years. It is estimated that CLN2 disease affects 14,000 individuals globally, and only about 20 infants per year are born with the disease in the U.S. Approval was supported by the phase II open-label study, which included eight children younger than three years old, which displayed a slower decline in motor function and disease onset. Brineura is infused under sterile conditions directly into the brain’s cerebrospinal fluid using an implanted reservoir and catheter. The recommended dose is 300mg administered over four and one-half hours every two weeks. The label carries a boxed warning for hypersensitivity reactions, including anaphylaxis. Once updated, the full prescribing information should be available on the company’s website, found here.
Xeomin Approved for Simultaneous Treatment of Upper Facial Lines
Merz Aesthetics received FDA approval on July 23, 2024, for the use of Xeomin® (incobotulinumtoxinA) to improve the appearance of moderate to severe upper facial lines, including forehead lines, glabellar (frown) lines and lateral canthal lines (crow’s feet). It’s a neuromuscular blocking agent that temporarily inhibits muscle contractions to smooth the upper facial lines. For cosmetic uses, Xeomin is administered by a healthcare professional in four units per intramuscular (IM) injection. When treating all three areas simultaneously, the maximum recommended dose is 64 Units. When not treated simultaneously, the maximum doses are 20 Units for glabellar lines, 40 Units for horizontal forehead lines, and 24 Units for lateral canthal lines (12 Units per side). Retreatment with Xeomin should not occur more frequently than every three months. All botulinum toxin products have Medication Guides and boxed warnings because they may cause widespread side effects, such as muscle weakness and vision changes if the drug migrates away from the areas where they are injected. Rarely, serious breathing or swallowing problems can occur. Other available botulinum products approved for cosmetic use are Botox® Cosmetic (onabotulinumtoxinA – Allergan Aesthetics), Daxxify® (daxibotulinumtoxinA-lanm – Revance Therapeutics), Jeuveau™ (prabotulinumtoxinA-xvfs – Evolus) and Letybo® (letibotulinuntoxinA-wlbg- Hugel). None is interchangeable with any of the others. Full prescribing information is available here.