Accelerated, rather than full, approvals were prominent. As usual, cancer registrations predominated—including Amgen’s Lumakras, a first-in-class covalent targeter of KRAS in lung cancer. The other big news was the controversial go-ahead from the US Food and Drug Administration (FDA) for Biogen’s Alzheimer’s monoclonal antibody (mAb) Aduhelm, which later was given a narrower label by the agency; the approval prompted calls by the acting FDA head for a federal investigation into interactions between the drug developer and regulators. Less prominent, but also notable, was the approval of Truseltiq, a drug from the multi-asset play BridgeBio, providing validation for its business model. There were setbacks for two COVID-19 products, as well as the gene therapy timrepigene emparvovec for the eye disease choroideremia. FDA decisions coming up include new disease-modulating drugs in cervical cancer, myasthenia gravis and leukopenia.

Historic US regulatory approvals by disease group

Oncology continues as the perennial leader.

*Partial year to 30 June.

Upcoming catalysts (4Q21)

Drug / company

Indication

Drug information

Tisotumab vedotin / Seagen

Cervical cancer

10/8/2021 FDA PDUFA date for this antibody–drug conjugate of a human IgG1κ mAb targeting human tissue factor conjugated to monomethyl auristatin E

Plinabulin / BeyondSpring

Neutropenia, leukopenia

11/30/2021 FDA PDUFA date for this small-molecule halimide derivative with selective immunomodulating microtubule-binding agent properties derived from marine Aspergillus sp.

Palovarotene / Ipsen

Fibrodysplasia ossificans progressiva

11/30/2021and 11/01/2021 FDA PDUFA and CHMP opinion dates for this selective small-molecule agonist of retinoic acid receptor-γ

Efgartigimod / Argenx

Myasthenia gravis

12/17/2021 FDA PDUFA date for this human IgG1 Fc fragment optimized to bind neonatal Fc receptor delivered using recombinant human hyaluronidase enzyme

Balstilimab / Agenus

Cervical cancer

12/16/2021 FDA PDUFA date for this fully human IgG4 mAb against programmed death ligand 1 (PD -1)

  1. PDUFA, Prescription Drug User Fee Act; CHMP, Committee for Medicinal Products for Human Use (Europe). Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com)

Notable regulatory setbacks (2Q21)

Drug / company

Indication

Drug information

Pegunigalsidase alfa / Chiesi Farmaceutici

Fabry’s disease

4/28/2021 FDA issued a complete response letter for this PEGylated recombinant α-galactosidase A produced in a carrot (Daucus carota) expression system because travel restrictions caused delays in inspection

CD24Fc / Merck

COVID-19 treatment

4/15/2021 Because of an FDA request for more clinical data, company halted development of this recombinant fusion protein comprising the extracellular domain of human CD24 linked to the human IgG1 Fc domain, which binds to DAMPs (danger-associated molecular patterns) in cellular debris, preventing their interaction with Toll-like receptors

Arimoclomol citrate / Orphazyme

Niemann–Pick disease

6/18/2021 FDA issued a complete response letter for this small-molecule (N-[(2R)-2-hydroxy-3-(1-piperidyl)propoxy]pyridine-3-carboximidoyl chloride, 1-oxide) activator of molecular chaperones, requesting more information on the interpretation of the 5-domain clinical severity scale

AdCovid / Altimmune

COVID prevention

6/29/2021 Company suspended trials of this intranasally administered replication-defective adenovirus 5 vector encoding S protein vaccine due to a low immune response

Timrepigene emparvovec / Biogen

Choroideremia

6/14/2021 Company suspended trials of this adeno-associated virus serotype 2 (AAV-2) vector containing CHM, which encodes the Rab escort protein-1, as it failed to meet primary endpoint of better than 15-letter improvement in visual acuity

  1. Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com) and company press releases

Notable clinical trial results (2Q21)

Drug / company

Indication

Drug information

Efgartigimod / Argenx

Myasthenia gravis

6/16/2021 In a phase 3 double-blind, placebo-controlled trial, patients receiving this human IgG1 Fc antibody fragment that binds neonatal Fc receptor, delivered using recombinant human hyaluronidase, had at least a two-point improvement in daily living score (Lancet Neurol. 20, 526–536, 2021)

Tezepelumab / Amgen

Asthma

5/13/2021 In a phase 3 double-blind, placebo-controlled trial of this human IgG2 mAb targeting thymic stromal lymphopoietin, patients with severe asthma had fewer exacerbations and better lung function and quality of life (N. Engl. J. Med. 384, 1800–1809, 2021)

Sutimlimab / Sanofi

Autoimmune hemolytic anemia

4/7/2021 In an open-label trial of this humanized IgG4 mAb against complement factor C1s, upstream inhibition of complement pathway halted hemolysis, increased hemoglobin levels and reduced fatigue (N. Engl. J. Med. 384, 1323–1334, 2021)

Omidubicel / Gamida Cell

Bone marrow transplant and stem cell transplant

6/22/2021 In a phase 3 trial of umbilical cord blood–derived stem and progenitor cells expanded ex vivo using nicotinamide (a sirtuin-1 modulator), transplant patients had faster hematopoietic recovery and fewer transplant-related complications than those treated with standard of care (umbilical cord blood) (Blood https://doi.org/10.1182/blood.2021011719, 2021)

Upadacitinib / AbbVie

Atopic dermatitis

5/20/2021 In randomized placebo-controlled trials of this small-molecule preferential JAK1 or JAK1/3 inhibitor, all primary and secondary endpoints were met with treatment combined with topical steroids compared with placebo plus topical steroids (Lancet https://doi.org/10.1016/S0140-6736(21)00588-2, 2021)

Xeljanz / Pfizer

COVID-19 treatment

6/16/2021 In this randomized, placebo-controlled trial of hospitalized patients not yet on ventilator, patients receiving this orally active small-molecule inhibitor of JAKs 1, 2 and 3 had significantly reduced rate of progression to respiratory failure or death (18.1% versus 29.0%) (N. Eng. J. Med. https://doi.org/10.1056/NEJMoa2101643, 2021)

  1. JAK, Janus-activated kinase. Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com)

Notable drug approvals (2Q21)

Drug / company

Indication

Drug information

Jemperli (dostarlimab-gxly) / GlaxoSmithKline

Uterine (endometrial) cancer

4/22/2021 FDA granted accelerated approval to this humanized IgG4 mAb against PD1

Zynlonta (loncastuximab tesirine-lpyl) / ADC Therapeutics

Diffuse large B-cell lymphoma, non-Hodgkin’s lymphoma

4/23/2021 FDA granted accelerated approval to humanized IgG1 mAb targeting CD19 conjugated to tesirine (a SG3199 warhead with a pyrrolobenzodiazepine dimer linker)

Rybrevant (amivantamab-vmjw) / Johnson & Johnson

Non-small-cell lung cancer

5/21/2021 FDA granted accelerated approval for this human IgG1 bispecific mAb targeting epidermal growth factor receptor and cMet

Lumakras (sotorasib) / Amgen

Non-small-cell lung cancer

5/28/2021 FDA granted accelerated approval for this first-in-class small-molecule covalent KRAS GTPase inhibitor for patients with a G12C mutation

Truseltiq (infigratinib) / BridgeBio Pharma

Biliary tract cancer

5/28/2021 FDA granted accelerated approval to this small molecule ATP competitive tyrosine kinase inhibitor of fibroblast growth factor receptor 1

Aduhelm (aducanumab) / Biogen

Alzheimer’s disease

6/7/2021 FDA granted accelerated approval to this fully human IgG1 mAb against a conformational epitope on β-amyloid plaques

  1. Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com)