The FDA has approved the oral kinase inhibitor encorafenib (Braftovi – Pfizer), in combination with the epidermal growth factor receptor (EGFR) inhibitor cetuximab (Erbitux), for treatment of adults with metastatic colorectal cancer (CRC) with a BRAF V600E mutation. Encorafenib was approved in 2018 for use with the mitogen-activated kinase (MEK) inhibitor binimetinib (Mektovi) for treatment of unresectable or metastatic melanoma with a BRAF V600E or V600K mutation.

The FDA has approved the oral tyrosine kinase inhibitor avapritinib (Ayvakit – Blueprint Medicines) for treatment of unresectable or metastatic gastrointestinal stromal tumors (GISTs) harboring a platelet-derived growth factor receptor alpha (PDGFRA) D842V or other PDGFRA exon 18 mutation. Avapritinib is the first drug to be approved for this indication in the US.

Casimersen (Amondys 45 – Sarepta), an IV antisense oligonucleotide, has received accelerated approval from the FDA for treatment of Duchenne muscular dystrophy (DMD) in patients who have mutations of the dystrophin gene that are amenable to exon 45 skipping (DMD-45), which occur in ~8% of DMD cases. Casimersen is the first drug to be approved for this indication and the fifth to be approved for treatment of DMD; the IV antisense oligonucleotides eteplirsen (Exondys 51), golodirsen (Vyondys 53), and viltolarsen (Viltepso) and the oral corticosteroid deflazacort (Emflaza) were...

Aducanumab-avwa (Aduhelm – Biogen/Eisai), an IV amyloid beta-directed monoclonal antibody, has received accelerated approval from the FDA for treatment of Alzheimer's disease. The approval was based on the surrogate endpoint of reduction in amyloid beta plaques in the brain. The manufacturer is required to conduct an additional randomized controlled trial to establish that reducing amyloid beta plaques with aducanumab improves clinical outcomes in patients with Alzheimer's disease.

Efgartigimod alfa-fcab (Vyvgart – Argenx), a first-in-class neonatal Fc receptor (FcRn) antagonist, has been approved by the FDA for IV treatment of generalized myasthenia gravis in adults who are anti-acetylcholine receptor (AChR) antibody positive. The IV complement inhibitor eculizumab (Soliris) was approved for the same indication in 2017.

The Bruton's tyrosine kinase (BTK) inhibitor pirtobrutinib (Jaypirca – Lilly) has received accelerated approval from the FDA for treatment of relapsed or refractory mantle cell lymphoma (MCL) in adults who received ≥2 prior lines of systemic therapy, including a BTK inhibitor. Accelerated approval was based on the response rate. The BTK inhibitors ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa) are also approved for treatment of MCL.

Since our initial review of the oral lipid-lowering adenosine triphosphate-citrate lyase (ACL) inhibitor bempedoic acid (Nexletol – Esperion) in 2020, cardiovascular outcomes data in statin-intolerant patients have become available.

The oral kinase inhibitors dabrafenib (Tafinlar – GSK) and trametinib (Mekinist – Novartis) have been approved by the FDA for use together for a sixth indication: treatment of low-grade glioma (LGG) with a BRAF V600E mutation in patients ≥1 years old who require systemic therapy. This combination is the first systemic therapy to be approved in the US for first-line treatment of LGG with a BRAF V600E mutation in pediatric patients. The FDA also approved new oral formulations of both drugs for patients who are unable to swallow dabrafenib capsules or trametinib...

The investigational anti-complement component 5a (C5a) antibody vilobelimab (Gohibic – InflaRx) has been granted an FDA Emergency Use Authorization (EUA) for IV treatment of hospitalized adults with COVID-19 beginning within 48 hours after invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) is started. Vilobelimab is the first anti-C5a antibody to become available in the US.

The oral gonadotropin-releasing hormone (GnRH) receptor antagonist relugolix (Orgovyx – Myovant Sciences/Pfizer) has been approved by the FDA for treatment of advanced prostate cancer in adults. It is the first oral GnRH receptor antagonist to become available in the US; degarelix (Firmagon), an injectable GnRH receptor antagonist, has been available since 2008 for the same indication.