Novel FDA Drug Approvals 2Q 2023

26 new drugs approved by the FDA’s Center for Drug Evaluation and Research (CDER) for 1H! Lots of exciting new mechanisms and modalities.

Highlights from the 2Q include –

💉 Tofersen (Qalsody), an antisense oligonucleotide indicated for the treatment of adult amyotrophic lateral sclerosis caused by SOD1 mutation.

💉 Pegunigalsidase alfa (Elfabrio), a recombinant form of human α-galactosidase-A indicated for long-term enzyme replacement therapy in patients with Fabry disease.

💊 Fezolinetant (Veozah), a selective neurokinin-3 (NK3) receptor antagonist used to treat moderate to severe vasomotor symptoms due to menopause.

👁 Perfluorohexyloctane (Miebo) is a drug used to treat dry eye disease. Check out structure! Mechanism unknown.

💉Epcoritamab (Epkinly), a bispecific CD20-directed CD3 T-cell engager used to treat relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in adults.

💊 Sulbactam/durlobactam (Xacduro), a co-packaged medication used for the treatment of bacterial pneumonia caused by Acinetobacter baumannii-calcoaceticus complex. It contains sulbactam, a beta-lactam antibacterial and beta-lactamase inhibitor; and durlobactam, a beta-lactamase inhibitor.

💊 Nirmatrelvir/ritonavir (Paxlovid), a co-packaged medication used as a treatment for COVID‑19. It contains the antiviral medications nirmatrelvir and ritonavir. Nirmatrelvir is a SARS-CoV-2 main protease inhibitor while ritonavir is a HIV-1 protease inhibitor and strong CYP3A4 inhibitor.

💉Flotufolastat F-18 (Posluma), a radiopharmaceutical diagnostic agent used in PET imaging to visualize PSMA-positive lesions in men with prostate cancer with suspected metastasis or recurrence.

💊 Sotagliflozin (Inpefa), a dual SGLT1/2 inhibitor used to reduce the risk of CV, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors

💉Glofitamab (Columvi), a bispecific mAb directed against CD20 and CD3 which is used for the treatment of relapsed or refractory diffuse large B-cell lymphoma.

💊 Ritlecitinib (Litfulo), a dual JAK3/TEC kinase family inhibitor used to treat severe alopecia areata in adults and adolescents 12 years and older.

💉Rozanolixizumab (Rystiggo), a humanized mAb targeting the human neonatal Fc receptor (FcRn) used to treat generalized myasthenia gravis.

💉Somatrogon (Ngenla), a long-acting recombinant human growth hormone used as the long-term treatment of pediatric patients who have growth failure due to growth hormone deficiency.

Again, a fascinating collection from Chris de Savi!

Targeted protein degradation (TPD)

Clinical Degrader Drugs 
Targeted protein degradation (TPD) is an emerging field in drug discovery that aims to selectively remove disease-causing proteins from cells. By directly targeting and eliminating proteins, TPD has the potential to address a wider range of disease targets, including those that have been traditionally considered “undruggable.”
Many highly selective PROTAC molecules with improved drug-like properties are entering clinical trials.
Some of the most exciting compounds being profiled are highlighted below

💊Vepdegrestrant (ARV-471), an orally bioavailable estrogen receptor (ER) protein degrader for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer.

💊Bavdegalutamide (ARV-110), an orally bioavailable androgen receptor (AR) protein degrader for the treatment of metastatic castration-resistant prostate cancer (mCRPC).

💊ARV-766, an orally bioavailable AR degrader for the treatment of mCRPC.

💊NX-2127, an orally bioavailable Bruton’s tyrosine kinase (BTK), Ikaros (IKZF1) and Aiolos (IKZF3) degrader for the treatment of R/R B cell malignancies.

💊NX-5948, an orally bioavailable BTK degrader for the treatment of R/R B cell malignancies.

💉DT-2216, an IV administered selective B-cell lymphoma-extra large (Bcl-XL) protein degrader for the treatment of T-cell lymphomas.

💉FHD-609, an IV administered BRD9 protein degrader for the treatment of synovial sarcoma.

💊CFT1946, an orally bioavailable mutant BRAF kinase protein degrader for the treatment of various BRAF V600E-driven cancers.

💊CFT8634, an orally bioavailable BRD9 protein degrader for the treatment of synovial sarcoma.

💊KT-474, an orally bioavailable IRAK4 protein degrader for the treatment hidradenitis suppurativa (HS) and atopic dermatitis (AD).

💉KT-413, an IV administered IRAK4, IKZF1 and IKZF3 protein degrader for the treatment of  MYD88-mutant B cell lymphomas.

💉KT-333, an IV administered STAT3 protein degrader for the treatment of Peripheral T-cell Lymphoma (PTCL).

💉KT-253, an IV administered MDM2 protein degrader for the treatment of r/r high grade myeloid malignancies and solid tumors.


💉SD-36, an IV administered STAT3 tool protein degrader.

💉MD-224, an IV administered MDM2 tool protein degrader.

Another amazing summary from Chris De Savi

First-in-Class Small Molecule Drug Approvals of 2022

First-in-Class Small Molecule Drug Approvals of 2022
Great collection by Drug Hunter.

Of the 36 novel small-molecule and large-molecule drugs approved by the FDA in 2022, 18 were first-in-class approvals, including 9 small molecules (excluding atoms).

Some of the notable small molecule first-in-class approvals of 2022 include:
Sunlenca (lenacapavir): the first approved drug targeting HIV-1 capsid, indicated for multi-drug resistant HIV with an impressive bi-annual dosing regimen (Gilead Sciences)

Sotyktu (deucravacitinib): the first approved de novo deuterated drug – an oral, allosteric tyrosine kinase 2 (TYK2) inhibitor for moderate-to-severe plaque psoriasis (Bristol Myers Squibb)

Ztalmy (ganaxolone): the first neurosteroid to be studied for epilepsy, approved for treating seizures in cyclin-dependent kinase-like 5 deficiency disorder, an oral GABA-A receptor modulator (Marinus Pharma) – a cyclodextrin-enabled formulation

Pyrukynd (mitapivat): the first approved therapeutic for pyruvate kinase (PK) deficiency – an oral pyruvate kinase activator that improves hemolytic anemia (Agios Pharmaceuticals)

Voquezna (vonoprazan): the first potassium-competitive acid blocker that acts via reversible potassium-competitive ion binding, approved for Helicobacter pylori infection (Phathom Pharmaceuticals)

See the full article here.