FDA Updates

The drug is tebentafusp-tebn (Kimmtrak, from Immunocore Limited), which acts as a bispecific gp100 peptide-HLA-directed CD3 T-cell engager. It is the first of a novel class of T-cell receptor (TCR) bispecific immunotherapies under development at the company.

It is also the first and only therapy for the treatment of unresectable or metastatic uveal melanoma to be approved by the FDA, and it is the first therapy to demonstrate a survival benefit to patients with this disease. However, the indication specifies that the drug is for use only in patients who are HLA-A*02:01-positive.

Source: Immunocore

The FDA issued approval for extended-release injectable cabotegravir (Apretude, CAB-LA) for use in at-risk adults and adolescents weighing at least 35 kilograms (77 pounds) for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV.

The priority review approval was based on phase 2b-3 clinical trial data submitted to the agency this past August, after one of the studies was stopped early because of encouraging efficacy results of the first pre-planned interim endpoint analysis.

Apretude is given first as two initiation injections administered one month apart, and then every two months thereafter. Patients can either start their treatment with Apretude or take oral cabotegravir (Vocabria) for four weeks to assess how well they tolerate the drug.

Source: FDA.gov

The US FDA has approved efgartigimod (Brand name: Vygart) a first-in-class, targeted therapy for adults with generalized myasthenia gravis (gMG) who test positive for the antiacetylcholine receptor (AChR) antibody.

Efgartigimod is an antibody fragment designed to reduce pathogenic IgG antibodies and block the IgG recycling process in patients with gMG. The novel agent binds to the neonatal Fc receptor (FcRn), which is widely expressed throughout the body and plays a central role in rescuing IgG antibodies from degradation. Blocking FcRn reduces IgG antibody levels.

The most common side effects associated with the use of Vyvgart include respiratory tract infections, headache, and urinary tract infections. As Vyvgart causes a reduction in IgG levels, the risk of infections may increase. Hypersensitivity reactions such as eyelid swelling, shortness of breath, and rash have occurred. If a hypersensitivity reaction occurs, discontinue the infusion and institute appropriate therapy.

Source: FDA

PreHevbrio [Hepatitis B Vaccine (Recombinant)]: contains the S, pre-S2, and pre-S1 HBV surface antigens, and is the only approved 3-antigen HBV vaccine for adults in the U.S.A.

INDICATIONS AND USAGE: PREHEVBRIO is indicated for prevention of infection caused by all known subtypes of hepatitis B virus. PREHEVBRIO is approved for use in adults 18 years of age and older.

DOSAGE AND ADMINISTRATION :For intramuscular injection. Administer a series of three doses (1.0 mL each) of PREHEVBRIO on a 0-, 1 and 6-month schedule.

CONTRAINDICATIONS: Severe allergic reaction (e.g., anaphylaxis) after a previous dose of any hepatitis B vaccine or to any component of PREHEVBRIO.

ADVERSE REACTIONS: Injection site pain, tenderness, headache (most common), fatigue and myalgia.

Source: FDA

The US Food and Drug Administration has approved pembrolizumab (Keytruda) for the adjuvant treatment of stage IIB and IIC melanoma after complete resection in adults and children over age 12 years. The FDA also extended the approval to those with stage III disease. The FDA approval on December 3 was based on the first interim findings from the randomized, placebo-controlled KEYNOTE-716 trial, which evaluated patients with stage IIB and IIC disease.

Source: Medscape

The US FDA has approved vosoritide (Voxzogo) daily injection for the treatment of children with achondroplasia. Indicated to increase linear growth in pediatric patients aged ≥5 years who have achondroplasia with open epiphyses.

Route: SC Inj.

MOA: Analog of C-type natriuretic peptide (CNP); this peptide binds to natriuretic-peptide receptor B (NPR B), which induces synthesis of cGMP molecules, which, in turn, inhibits the MAPK pathway.

Adverse Effects: Injection site erythema (75%), Injection site swelling (62%), Vomiting (27%), Injection site urticaria (25%), Arthralgia (15%), Decreased blood pressure (13%), Gastroenteritis (13%)

Source: Medscape

The U.S. FDA approved Besremi (ropeginterferon alfa-2b-njft) injection to treat adults with polycythemia vera, a blood disease that causes the overproduction of red blood cells. The excess cells thicken the blood, slowing blood flow and increasing the chance of blood clots.

Besremi has a longer half-life than do other pegylated interferon-alfas, allowing for dosing every 2 weeks instead of weekly.

Besremi can cause liver enzyme elevations, low levels of white blood cells, low levels of platelets, joint pain, fatigue, itching, upper airway infection, muscle pain and flu-like illness. Side effects may also include urinary tract infection, depression and transient ischemic attacks. May cause or worsen neuropsychiatric, autoimmune, ischemic and infectious diseases.

Source: FDA

The US FDA has granted an accelerated approval to mobocertinib for the treatment of patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations. The drug is limited to use in patients whose disease has progressed on or after platinum-based chemotherapy and who have had the EGFR exon20 insertion mutation detected on an FDA-approved test. Mobocertinib is the first oral tyrosine kinase inhibitor (TKI) specifically designed to target these mutations, which are less common than the more predominant EGFR mutations in this lung cancer. The most common adverse reactions (> 20%) were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain, according to the company. The prescribing information includes a boxed warning for QTc prolongation and Torsades de Pointes, and warnings and precautions for interstitial lung disease/pneumonitis, cardiac toxicity, and diarrhea.

Source: Medscape

The US FDA has approved the Vivistim System (MicroTransponder), a first-of-its kind vagus nerve stimulation (VNS) system intended to treat moderate-to-severe upper extremity motor deficits associated with chronic ischemic stroke. The Vivistim® System stimulates the vagus nerve while the patient is undergoing a rehabilitative movement, which tells the brain to “pay attention” to that movement. This simultaneous pairing of a specific movement with vagus nerve stimulation (VNS) strengthens motor circuits associated with the physical movement. Consistently pairing VNS with specific neural circuits helps rebuild those circuits and the brain relearns the commands to enable the muscles to perform specific tasks and can strengthen those muscles as well. This simultaneous pairing of muscle movement with VNS strengthens the neural circuits in the brain. Over time, a patient may regain upper limb function.

Source: MicroTransponder

The approval covers all three brivaracetam (BRIVIACT) formulations (tablets, oral solution, and IV) and marks the first time the IV formulation will be available for children.

Dosage:

• Dose for adults (16 Years and Older): The recommended starting dosage for monotherapy or adjunctive therapy is 50 mg twice daily (100 mg per day). Based on individual patient tolerability and therapeutic response, the dosage may be adjusted down to 25 mg twice daily (50 mg per day) or up to 100 mg twice daily (200 mg per day).
• Pediatric Patients (1 Month to less than 16 Years): The recommended
  dosage is based on body weight and is administered orally twice daily.

Adverse reaction: Most common adverse reactions (at least 5% for BRIVIACT and at least 2% more frequently than placebo) are somnolence/sedation, dizziness, fatigue, and nausea/vomiting.

Source: UCB