Regulatory paths are rarely straightforward, especially for complex modalities in complex diseases. The plight of anti-amyloid antibodies in Alzheimer’s disease remains unpredictable after two FDA decisions in January: FDA asked Eli Lilly for more data from patients with year-long exposure to donanemab before it would consider approval, but gave Biogen and Eisai’s lecanemab an accelerated approval. There were three approvals for treatments for rare or ultra-rare diseases in the first quarter of 2023: Chiesi Farmaceutici’s α-mannosidase replacement enzyme Lamzede and small-molecule treatments for Rett syndrome (Daybue from Acadia Pharma) and Friedreich’s ataxia (Skyclarys from Reata Pharmaceuticals). The blood-clotting market is undergoing fast technological change: Sanofi’s once-weekly factor VIII analog Altuviiio received FDA approval in February while Novo Nordisk’s antibody prophylactic for hemophilia A or B and BioMarin’s Roctavian factor VIII gene therapy both have PDUFA dates in the next several months. But there were setbacks for Graphite Bio’s gene-edited sickle cell disease treatment and Sarepta’s microdystrophin gene therapy.

Historic US regulatory approvals by drug class

Approvals on course to surpass 2022 total.

*New molecular entity (NME) class includes mainly small-molecule drugs, but also steroid, synthetic peptide and mixed compounds, excluding non-NME and new formulation. **Partial year to March 31. Source: US Food and Drug Administration.

Notable drug approvals (1Q23)



Drug information

Lamzede (velmanase alfa)/Chiesi Farmaceutici


2/16/2023 FDA approves this recombinant human α-mannosidase replacement enzyme

Leqembi (lecanemab)/Eisai, Biogen

Alzheimer’s disease

1/6/2023 FDA gives accelerated approval to this humanized monoclonal IgG1 antibody against amyloid-β plaques

Daybue (trofinetide)/Acadia Pharmaceuticals

Rett syndrome

3/10/2023 FDA approves this analog of the amino-terminal tripeptide (glycine–proline–glutamate) of IGF-1

Skyclarys (omaveloxolone)/ Reata Pharmaceuticals

Friedreich’s ataxia

2/28/2023 FDA approves this small-molecule activator of Nrf2, which activates genes that promote mitochondrial function

Altuviiio (efanesoctocog alfa)/Sanofi

Hemophilia A

2/23/2023 FDA approves this fully recombinant extended-half-life factor VIII protein that can be dosed once-weekly

Jaypirca (pirtobrutinib)/Eli Lilly

Mantle cell lymphoma – non-Hodgkin lymphoma

1/27/2023 FDA grants accelerated approval for this small-molecule BTK inhibitor that binds reversibly to the kinase target, potentially limiting the emergence of drug resistance

Brenzavvy (bexagliflozin)/ TheracosBio

Diabetes mellitus, type 2

1/23/2023 FDA approves this sodium–glucose co-transporter 2 (SGLT2) inhibitor in adults. In 2022, FDA approved it for diabetes in cats

Zynyz (retifanlimab-dlwr)/Incyte

Merkel cell carcinoma

3/22/2023 FDA gives accelerated approval for this humanized IgG4κ anti-PD-1 mAb

Jesduvroq (daprodustat)/GSK

Anemia due to dialysis-dependent chronic kidney disease

2/1/2023 FDA approves this oral small-molecule prolyl hydroxylase inhibitor that stabilizes hypoxia-inducible factors, leading to erythropoietin gene transcription and the correction of anemia

  1. IgG, immunoglobulin G; IGF-1, insulin like growth factor 1; Nrf2, nuclear factor erythroid 2–related factor 2; BTK, Bruton’s tyrosine kinase; PD-1, programmed cell death 1; mAb, monoclonal antibody; SGLT2, sodium–glucose transporter 2. Source: BioMedTracker, a service of Sagient Research (

Upcoming catalysts (3Q23)



Drug information

Bimekizumab (Bimzelx)/UCB

Psoriatic arthritis

04/01/2023 FDA PDUFA date for this humanized bispecific IgG1 mAb that neutralizes IL-17A and IL-17F

Ryoncil (remestemcel-L)/ Mesoblast

Graft-versus-host disease

08/02/2023 FDA PDUFA date for this adult allogeneic, bone-marrow-derived mesenchymal stem cell treatment

Lumevoq/GenSight Biologics

Leber’s hereditary optic neuropathy

7/1/2023 EMA CHMP opinion for this AAV-2 gene therapy encoding the wild-type ND4 gene

Concizumab/Novo Nordisk

Hemophilia A and B

09/01/2023 FDA PDUFA date for this humanized IgG4 mAb specific for the K2 domain of TF1 inhibitor peptide

Nedosiran/Novo Nordisk


09/01/2023 FDA PDUFA date for this second-generation siRNA created using GalXC technology, with an extended Dicer substrate siRNA (DsiRNA-EX) that silences the LDHA gene


Hemophilia A

06/30/2023 FDA PDUFA date for this AAV5-based gene therapy vector that expresses a recombinant version of human factor VIII under the control of a liver-specific promoter


CHAPLE syndrome

08/20/2023 FDA PDUFA date for this fully human monoclonal antibody to human complement C5 produced with IgG4P Fc domains


Fungal infections

6/1/2023 FDA PDUFA date for this orotomide inhibitor of dihydroorotate dehydrogenase

  1. Il-15, interleukin-15; AAV, adeno-associated virus; ND4, NADH dehydrogenase 4 gene; TF-1, tissue factor pathway 1; siRNA, short interfering RNA; PDUFA, Prescription Drug User Fee Act; EMA, European Medicines Agency; CHMP, Committee for Medicinal Products for Human Use. Source: BioMedTracker, a service of Sagient Research (

Notable regulatory setbacks (1Q23)



Drug information

Donanemab/Eli Lilly

Alzheimer’s disease

1/19/2023 FDA issues a CRL for the application for accelerated approval for this humanized IgG1 mAb targeting amyloid-βp3–42, the N-terminally truncated pyroglutamate-3 isoform, because of the small number of patients with 12 months of drug exposure

Omecamtiv mecarbil/Cytokinetics

Chronic heart failure

2/28/2023 FDA issues a CRL for this small-molecule cardiac myosin activator because of lack of substantial evidence that risk of heart failure was reduced; the company will conduct no further clinical trials

Delandistrogene moxeparvovec/Sarepta

Duchenne muscular dystrophy

3/16/2023 FDA announces plans to hold an advisory committee meeting for this AAVrh74.MHCK7.micro-dystrophin gene therapy on 12 May 2023


Cutaneous T cell lymphoma

2/14/2023 FDA issues a refuse-to-file letter for this small-molecule synthetic photosensitizer as a result of an incomplete NDA

Nula-cel/Graphite Bio

Sickle cell anemia

1/5/2023 Company discontinues phase 1/2 trial of nulabeglogene autogedtemcel (nula-cel) for sickle cell disease owing to a serious adverse event in the first patient dosed. The company will restructure, reducing workforce by around 50%.

  1. CRL, complete response letter; IgG, immunoglobulin G; mAb, monoclonal antibody; NDA, New Drug Application. Source: BioMedTracker, a service of Sagient Research (

Notable clinical trial results (1Q23)



Drug information

PEGylated interferon lambda/Eiger BioPharmaceuticals

COVID-19 treatment

2/8/2023 In a randomized, controlled, adaptive trial of vaccinated people with COVID-19, 2.7% of treated required hospitalization versus 5.6% receiving placebo (N. Engl. J. Med. 388, 518–528, 2023)



1/27/2023 In a randomized, controlled, double-blind phase 3 study, this inhibitor of JAK1/2 and ACVR1 provided significant improvement in symptoms compared to standard of care (Lancet, 2023)


Desmoid tumors

3/8/2023 In a phase 3 double-blind, randomized, placebo-controlled trial, this selective, reversible, non-competitive small-molecule inhibitor of γ-secretase yielded a significant increase in progression-free survival over placebo (N. Engl. J. Med. 388, 898–912, 2023)

Leriglitazone/Minoryx Therapeutics


1/19/2023 A multi-center, double-blind, placebo-controlled trial of this small-molecule PPAR-γ inhibitor met secondary endpoints of balance, quality of life and tolerability, and no treated patients had progressive disease (Lancet, 2023)

Garadacimab/CSL Behring

Hereditary angioedema

2/28/2023 In a double-blind, randomized, placebo-controlled, multicenter, parallel-group study of this fully human recombinant factor XIIa antagonist monoclonal antibody, patients taking garadacimab (N = 39) experienced a statistically lower monthly attack rate compared to placebo over the 6-month study (Lancet, 2023)

  1. JAK1/2, Janus kinase 1 and 2; ACVR1, activin A receptor type I; PPAR, peroxisome proliferator-activated receptor. Source: BioMedTracker, a service of Sagient Research (