FDA Updates

The US FDA has approved dabrafenib + trametinib for adult and pediatric patients aged 6 years and older with unresectable or metastatic solid tumors with the BRAF V600E mutation whose disease has progressed following prior treatment and who have no satisfactory alternative treatment options.

The combination represents “the first and only BRAF/MEK inhibitor to be approved with a tumor-agnostic indication for solid tumors carrying the BRAF V600E mutation, which drives tumor growth in more than 20 different tumor types, and it is the only BRAF/MEK inhibitor approved for use in pediatric patients.

The combination already carries indications for BRAF-mutated melanoma, non–small cell lung cancer, and thyroid cancer. The new approval was based on two adult trials and one pediatric trial that showed an overall response benefit for patients with high- and low-grade gliomas, biliary tract cancers, and certain gynecologic and gastrointestinal cancers.

Source: Medscape

The US FDA has approved Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for BBS, a rare genetic disorder that impairs a hunger signal along the melanocortin-4 receptor (MC4R) pathway.

Individuals with Bardet-Biedl Syndrome typically have obesity that starts at age 1 along with insatiable hunger (hyperphagia). Available weight management options are generally unsuccessful. Other symptoms may include retinal degeneration, reduced kidney function, or extra digits of the hands or feet.

The most common adverse reactions (with an incidence ≥ 20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.

Source: Medscape

The US FDA has approved the IN.PACT 018 drug-coated balloon (DCB) for the treatment of peripheral arterial disease.

The paclitaxel-coated balloon is indicated for percutaneous transluminal angioplasty of de novo, restenotic, or in-stent restenotic lesions up to 360 mm in length with vessel diameters of 4 to 7 mm, located in the superficial femoral and popliteal arteries.

The IN.PACT 018 DCB is built on the same technology as the IN.PACT Admiral DCB (0.035 inch guidewire compatible), but is engineered to cross tight lesions, provide better deliverability, and is 0.018 inch guidewire compatible.

Source: Medscape

Immunotherapy with nivolumab (Opdivo) is now approved in the United States for first-line use in the treatment of unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).

The new approval for the drug, a programmed cell death ligand-1 (PD-L1) inhibitor, is for use in this patient population regardless of PD-L1 status. The indication also specifies that nivolumab is to be used together with chemotherapy (with a fluoropyrimidine- and platinum-containing regimen) or in combination with ipilimumab (Yervoy), an immunotherapy with a different mechanism of action.

Source: Medscape

The FDA approved a combination nivolumab/relatlimab-rmbw immune checkpoint inhibitor (Opdualag) for unresectable or metastatic melanoma in adults and children 12 years or older.

Dose: 480 mg nivolumab + 160 mg relatlimab IV every 4 weeks.

Adverse effects: Musculoskeletal pain, fatigue, rash, pruritus, and diarrhea were the most common adverse reactions with combination nivolumab/relatlimab, occurring in 20% or more of RELATIVITY-047 trial participants. Adrenal insufficiency, anemia, colitis, pneumonia, and myocardial infarction were the most frequent serious adverse reactions, but each occurred in less than 2% of patients. There were three fatal adverse events in the trial due to hemophagocytic lymphohistiocytosis, acute lung edema, and pneumonitis.

Source: BMS

Anifrolumab, an inhibitor of type 1 interferons, received approval from the Food and Drug Administration for the treatment of adults with moderate to severe systemic lupus erythematosus (SLE) who are receiving standard therapy.

Dose: 300 mg concentrate for solution for infusion.

Adverse Effects: The most common adverse reactions are upper respiratory tract infection, bronchitis, infusion-related reaction, and herpes zoster. The most common serious adverse reaction was herpes zoster.

Source: FDA

The US FDA approves first drug for Cold Agglutinin Disease. Sutimlimab-jome (Brand name: ENJAYMO) is a classical complement inhibitor indicated to decrease the need for red blood cell (RBC) transfusion due to hemolysis in adults with cold agglutinin disease.

Dose:  Injection: 1,100 mg/22 mL (50 mg/mL) in a single-dose vial

Adverse effects: Most common adverse reactions (incidence ≥10%) are respiratory tract infection, viral infection, diarrhea, dyspepsia, cough, arthralgia, arthritis, and
peripheral edema.

Source: FDA

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