The FDA Approves New Botulinum Product

Hugel was granted approval by the U.S. Food and Drug Administration (FDA) on Feb. 29, 2024, for Letybo^® (letibotulinuntoxinA-wlbg) injection. The neurotoxin is indicated for cosmetic use to temporarily smooth glabellar (frown) lines on the forehead. It will be injected by a healthcare professional intramuscularly (IM) into five separate sites on the forehead at a dose of 4 Units in each injection no more than once every 90 days. Although the total recommended dose for each treatment is 20 Units, it will be supplied in 50-unit and 100-Unit single-use vials for reconstitution. Beginning later in 2024, shipments will go directly to providers such as plastic surgeons and cosmetic dermatologist clinics. All botulinum toxin products have Medication Guides and boxed warnings because they potentially may cause widespread side effects, such as muscle weakness and vision changes if they migrate away from the areas where they are injected. Rarely, serious breathing or swallowing problems can occur. Side effects may not be evident until several months after the product has been injected. Other available botulinum products that have the same indication are Botox^® Cosmetic (onabotulinumtoxinA – Allergan Aesthetics), Daxxify^® (daxibotulinumtoxinA-lanm – Revance Therapeutics), Jeuveau^™ (prabotulinumtoxinA-xvfs – Evolus) and Xeomin^® (incobotulinumtoxinA – Merz Pharmaceuticals). None is interchangeable with any of the others. Look here for prescribing information.

First Biosimilars Approved for Prolia and Xgeva

On March 5, 2024, the FDA approved Sandoz’s biosimilars for Amgen’s receptor activator of nuclear factor kappa beta ligand (RANKL) inhibitor, denosumab. Jubbonti^® (denosumab-bbdz) injection is interchangeable with Prolia^® (denosumab), and Wyost^® (denosumab-bbdz) can be interchanged with Xgeva^® (denosumab). Jubbonti is given by a health professional as a 60mg subcutaneous (SC) injection once every six months. It treats osteoporosis for individuals whose risk of fractures is high, including some who are taking glucocorticoids or certain drugs to treat breast or prostate cancer. A boxed warning and a risk evaluation and mitigation strategy (REMs) caution that using Prolia may raise the risk of dangerous hypocalcemia (low levels of calcium in the blood) for patients who have chronic kidney disease (CKD). Wyost is indicated to prevent bone-related incidents for some patients who have multiple myeloma, bone metastases from solid tumors, giant cell tumors of the bone or hypercalcemia of malignancy. After loading doses, it is administered SC at 120mg once every month. Jubbonti and Wyost cannot be substituted for one another. Ongoing lawsuits will prevent their launch for the foreseeable future. For prescribing information, please refer to the respective links for Jubbonti and Wyost.

Second Actemra Biosimilar Approved

Fresenius Kabi received FDA approval on March 5, 2024, for Tyenne^® (tocilizumab-aazg), a biosimilar to Actemra^® (tocilizumab – Genentech). Tyenne is indicated for treating active, moderate to severe cases of rheumatoid arthritis (RA) and giant cell arteritis in adults, and active cases of polyarticular juvenile idiopathic arthritis (PJIA) and systemic juvenile idiopathic arthritis (SJIA) in patients who are as young as two years old. It can be used alone or combined with other anti-inflammatory drugs, such as methotrexate. It has a boxed warning because using any tocilizumab drug may increase the risk of opportunistic bacterial, fungal, viral or other infections. Before tocilizumab is started and during treatment with it, patients should be tested for tuberculosis (TB). Like Actemra, Tyenne will be available in vials for intravenous (IV) injections and in prefilled syringes and pen injector devices for SC use. Tofidence^™ (tocilizumab-bavi – Biogen) the first Actemra biosimilar that was approved in the U.S. on Sept. 29, 2023, will be released only as an IV form. Check here for its complete prescribing information.

Clobetasol Ophthalmic Suspension Approved

The FDA approved Formosa Pharmaceuticals/AimMax Therapeutics’ Clobetasol Propionate Ophthalmic Suspension, 0.05%, on March 4, 2024. Using the company’s proprietary nanoparticle technology, it is a reformulation of a high-strength topical corticosteroid widely used on the skin to treat conditions such as atopic dermatitis and vitiligo. As the first ophthalmic version of the drug, it is indicated to reduce pain and inflammation caused by eye surgeries such as cataract removal. One drop will be used in each affected eye twice a day beginning on the day after the surgery and lasting for a total of two weeks. Patients using it should have intraocular pressure (IOP) measured during use because increases in IOP may be caused by corticosteroids. The U.S. distributor, Eyenovia, plans a mid-2024 launch. Here is its prescribing information.

Rybrevant Receives Full and Expanded FDA Approval

Based on positive results from a mandated clinical trial and using Priority Review, the FDA converted its 2021 Accelerated Approval for Rybrevant^® (amivantamab-vmjw) to full approval on March 1, 2024. As monotherapy, it treats patients who have non-small cell lung cancer (NSCLC) that has epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as diagnosed with a companion diagnostic test, and that has returned or become resistant to prior or current platinum-based chemotherapy (chemo). At the same time, the FDA extended Rybrevant’s indication to include initial treatment in combination with chemo that includes carboplatin and pemetrexed for EGRF-mutated NSCLC. In the decisive clinical trial, the rates of cancer progression or death were 61% less for treatment patients using Rybrevant plus chemo than they were for patients just receiving chemo. Progression-free survival averaged 11.4 months and 6.7 months, respectively. The American Lung Association (ALA) estimated in 2020 that about 604,000 Americans have lung cancer with up to 85% of them having NSCLC. Rybrevant’s manufacturer, the Janssen Pharmaceutical Companies of Johnson & Johnson, further estimates that 10% to 15% of patients have NSCLC with EFGR exon 20 mutations susceptible to treatment with it. A bi-specific antibody that targets EGFR on the outside of cells, Rybrevant disrupts tumor growth. It is given as IV infusions with dosing based on body weight. When used alone, the Rybrevant dose of 1,050mg for patients weighing less than 80kg (176 pounds) is split between days one and two of the first week; then given on the first days of weeks two through five; and then shifted to once every two weeks beginning with week seven. Those weighing more than 80kg should receive doses of 1,400mg on the same dosage schedule. In combination with chemo, doses of Rybrevant for patients who weigh less than 80kg are 1,400mg divided between days one and two; then 1,400mg once a week for the next three weeks; and then increased at week seven to 1,750 once every three weeks. Heavier patients using both chemo and Rybrevant should get 1,750 – with the first dose divided between days one and two – weekly for the first four weeks and then 2,100mg once every three weeks beginning at week seven. Common adverse events (AEs) include rash, infusion-related reactions, muscle pain, nausea, fatigue, and edema. Patients should limit direct exposure to sunlight and use sunscreen to lower the risk of sunburn while using Rybrevant and for at least two months after treatment ends. Updated prescribing information is here.

Extended Opdivo Indication

The urothelial carcinoma indication for Opdivo^® (nivolumab) injection, an immune-oncology agent from Bristol Myers Squibb, was widened by the FDA on March 6, 2024. It now is indicated, along with the chemo drugs cisplatin and gemcitabine, as initial treatment for adults who have urothelial carcinoma that has metastasized or that cannot be removed by surgery. Previously, it was approved only for patients who already had been treated for that type of cancer. A programmed death receptor-1 (PD-1)-blocking antibody, Opdivo has indications for several other cancers, including some types of melanoma, small cell lung cancer (SCLC), and classic Hodgkin lymphoma. Along with Yervoy^® (ipilimumab) injection, it is indicated for first-line treatment of adult patients who have esophageal squamous cell carcinoma (ESCC) that cannot be removed surgically and that has spread or worsened, specific kinds of renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), non-small cell lung cancer (NSCLC) and microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC). Additionally, Opdivo is approved for use along with chemo which includes fluoropyrimidine and platinum-based drugs to treat ESCC. The FDA approved Opdivo’s extended urothelial carcinoma indication as a Priority Review and evaluated it under the rules of its Project Orbis and Real-Time Oncology Review (RTOR) programs, which all speed up evaluations for drugs that fill critical needs. Here is the current prescribing information.

Pediatric Indication Approved for Besponsa

The FDA awarded Pfizer a pediatric indication for Besponsa^™ (inotuzumab ozogamicin) injection on March 6, 2024. Originally approved by the FDA in August 2017, it was first indicated to treat adults who have relapsed or refractory B-cell precursor acute lymphoblastic leukemia (r/rALL). It now can be used to treat r/rALL for all patients who are at least one year old. The American Cancer Society estimates that approximately 60% of the 6,500 cases of ALL diagnosed annually in the U.S. are among children and teens. The CD-22-directed antibody-drug conjugate helps to block the spread of ALL by infiltrating cancer cells and causing them to disintegrate. Doses are given by IV infusions on 28-day cycles after three doses during the first cycle, which lasts only 21 days. Before each dose of Besponsa, patients should receive a corticosteroid, a fever reducer, and an antihistamine. During the infusions and for an hour or more after they finish, patients should be observed for any signs of breathing difficulty, fever, rash, or infusion reactions. A boxed warning outlines the risks of potentially fatal liver damage for patients using it as well as a higher chance of death for patients who use Besponsa after a hematopoietic stem cell transplant (HSCT). Go here for revised prescribing information.

New Indication for Juvéderm Voluma XC

In a press release dated March 5, 2024, the Allergan Aesthetics division of AbbVie, revealed that the FDA has approved another indication for one of its cosmetic fillers, Juvéderm^® Voluma^® XC. A hyaluronic acid gel implant, it is the first cosmetic injection that can be used to augment moderately to severely sunken areas (hollows) at the temples for adults aged 21 years and older. Like all products of its type, it will be introduced into the affected areas in several small amounts (typically 0.1mL to 0.2mL) as SC injections administered by a cosmetic surgeon or other specifically trained health provider in a medical setting. In clinical trials, most patients saw temple fullness last for a year or more although some needed touch-ups after several months. Some patients experience temporary mild-to-moderate side effects — mainly bruising, itching, lumpiness, pain, redness, or swelling after injections. Juvéderm Voluma XC also is approved by the FDA to increase volume in the cheek and chin areas. More information is here.

Opill Launched

The first over-the-counter (OTC) daily oral contraceptive, Opill^® (norgestrel – Perrigo) tablets, 0.075mg, is being shipped to retailers and it will be available for purchase as blister cards containing 28 tablets within the next few weeks. The suggested price is $19.99 for one month, $49.99 for three months, and $89.99 for six months. Taken once every day to prevent pregnancy for women of reproductive age, it is not an emergency contraceptive and it does not prevent sexually transmitted diseases. Opill does not include estrogen; its single progestin ingredient is 98% effective at disrupting implantation when taken continually. Although norgestrel has been FDA-approved to prevent pregnancy for 50 years, it previously has been available only with a prescription. Labeling for Opill warns against its use by individuals who have breast cancer or who already are pregnant. Those who have irregular periods, liver conditions, or any kind of cancer should consult with a healthcare provider before taking it. All other daily oral contraceptives currently remain prescription-only in the U.S. Product labeling for Opill is here.

First Over-the-Counter Continuous Blood Glucose Monitor Approved

Dexcom got FDA approval on March 5, 2024, to market a nonprescription continuous blood glucose monitor (CGM). Stelo by Dexcom is intended for individuals at least 18 years old, including those who have type 2 diabetes but who do not need insulin. The small sensor attaches to the upper arm and sends glucose readings to the wearer’s smart device every 15 minutes. Each sensor can last for as long as 15 days. Unlike the more comprehensive prescription-only Dexcom CGMs, Stelo will not alert wearers if blood sugar is too low. Its users are warned not to use data from the monitor to make any changes to their medications before consulting with a health professional. Launch is planned for the summer of 2024 and purchasers will pay cash for the units.

Inhaler Price Limit Boehringer Ingelheim announced on March 7, 2024, that it will reduce some list prices and restrict U. S. patients’ out-of-pocket (OOP) costs to $35 per month for each of the company’s inhalers. Starting on June 1, 2024, interested individuals can enroll in the program at the websites for each product. The offer includes the company’s therapies used to treat chronic obstructive pulmonary diseases (COPD), such as Atrovent^® HFA (ipratropium) Inhalation Aerosol, Combivent^® Respimat^® (ipratropium/albuterol) Inhalation Spray, Spiriva^® HandiHaler^® (tiotropium inhalation powder), Spiriva^® Respimat^® 2.5mcg Inhalation Spray, Stiolto^® Respimat^® (tiotropium/olodaterol) Inhalation Spray, and Striverdi^® Respimat^® (olodaterol) Inhalation Spray. Additionally, Spiriva Respimat 1.25mcg (tiotropium) Inhalation Spray is approved as a maintenance therapy for asthma. Individuals who have drug coverage through a federal government program such as Medicaid or Medicare are not eligible for Boehringer Ingelheim’s program.