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FDA approves Vabysmo™ (faricimab-svoa) for ophthalmic disorders

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On January 28, 2022, Genentech announced that the U.S. Food and Drug Administration has approved Vabysmo ™ (faricimab-svoa) for the treatment of wet, or neovascular, age-related macular degeneration (AMD) and diabetic macular edema (DME). Faricimab (RO6867461, RG7716) is an anti-vascular endothelial growth factor-A (VEGF-A) and anti-angiopoietin-2 (Ang-2) bispecific antibody derived from Roche’s CrossMab technology.

The approval was based in part on results from four Phase 3 studies in wet AMD and DME. The randomized, double-masked, and active comparator-controlled TENAYA (NCT03823287) and LUCERNE (NCT03823300) studies evaluated the effects of faricimab (6.0 mg administered at fixed intervals of every two, three, or four months) and aflibercept (Eylea®) (2.0 mg administered at fixed two-month intervals) in wet AMD patients. The primary endpoint of the studies, average change in best-corrected visual acuity (BCVA) from baseline through week 48, was met in both studies. The average vision gains from baseline in the faricimab arms were +5.8 and +6.6 letters, compared to +5.1 and +6.6 letters in the aflibercept arms, in the TENAYA and LUCERNE studies, respectively, demonstrating the non-inferiority of faricimab compared to aflibercept. The study also showed that faricimab’s treatment interval could be longer than that of aflibercept – nearly 80% of patients treated with faricimab were able to go three months or longer between treatments during the first year.

The 3-arm, randomized, double-masked, active comparator-controlled YOSEMITE (NCT03622580) and RHINE studies (NCT03622593) compared the effects of faricimab (6.0 mg administered at personalized treatment intervals (PTI) of up to four months or 6.0 mg administered at fixed two-month intervals) to those of aflibercept (2.0 mg administered at fixed two-month intervals) in DME patients. The primary endpoint, average change in BCVA score from baseline at one year, was met, with faricimab again showing non-inferiority in visual acuity gains compared to aflibercept. In the YOSEMITE study, the average vision gains from baseline were +11.6, +10.7, and +10.9 letters eye chart letters in the faricimab PTI, faricimab two-month, and aflibercept arms, respectively. The average vision gains from baseline were +10.8, +11.8, and +10.3 letters in the faricimab PTI, faricimab two-month, and aflibercept arms, respectively, in the RHINE study.

Further details for the TENAYA and LUCERNE and YOSEMITE and RHINE studies were published in The Lancet.

The European Medicines Agency has accepted the submission of a Marketing Authorisation Application for faricimab.

Vabysmo ™ is the 2nd antibody-based therapeutic granted a first approval for marketing in the EU or US in 2022. Explore our searchable table of antibody therapeutics approved in the EU or US for details.

Register now for our webinar on computational mining of immune receptor germline gene loci variation

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Registration for our next webinar, “Computational mining of immune receptor germline gene loci variation“, is now open!

B and T cell receptors play a critical role in responding to pathogens and vaccination, and in the pathology of several diseases of the immune system. Gene segments at the T cell receptor and immunoglobulin loci serve as templates for the generation and expression of T and B cell receptors and antibodies. Defining genetic variation within these highly polymorphic loci is critical to furthering our understanding of immunological diseases, and informing the design of vaccines and therapeutics. However, at the genomic level, these loci have been difficult to analyze due to their repetitive nature, rich in segmental duplications, simple repeats and retrotransposon elements. To overcome this complexity, several sequencing technologies and algorithms have been developed to more fully define the spectrum of genetic variation in these immune loci in human populations and other species. This webinar includes demonstrations of three orthogonal and complementary methods. First, Dr. Corcoran will present IgDiscover, an IG and TR adaptive immune repertoire sequencing (AIRR-seq) germline inference tool that has been in use for several years and applied to multiple species. The IgDiscover output is highly reproducible and can facilitate the comparison of multiple individuals in disease cohorts to identify disease associated allelic or structural variants. Ayelet Peres will present on VDJbase and RAbHIT, two bioinformatics tools for germline variation detection from AIRR-seq using population analysis and chromosomal phasing. These tools have been used to discover germline variations affecting the expressed repertoires. Finally, Dr. Rodriguez will demonstrate an approach using long-read sequencing and a bioinformatics tool, IGenotyper, to fully characterize both coding and non-coding single-nucleotide variants, small insertions and deletions, and structural variants across IG and TCR loci in a haplotype-specific manner. This will also include discussion on how IGenotyper is being applied to survey immune loci in non-human species.

Register here!

Tools and Software to be discussed:

  • IgDiscover analyzes antibody repertoires and discovers new V genes from high-throughput sequencing reads. Heavy chains, kappa and lambda light chains are supported (to discover VH, VK and VL genes).
  • VDJbase.org – a database of adaptive immune receptor genes, genotypes, and haplotypes.
  • RAbHIT – R tool for haplotype inference from BCR and TCR repertoires.
  • VDJbase pipeline –  BCR and TCR repertoires downstream analysis for VDJbase reports.
  • IGenotyper (or IG) was developed for PacBio capture data to assemble the Immunoglobulin Heavy Chain locus (IGH), genotype the IGH genes, and identify SNPs, indels and SVs within the IGH locus.

FDA approves KIMMTRAK® (tebentafusp-tebn) for unresectable or metastatic uveal melanoma

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On January 26, 2022, Immunocore Holdings plc announced the approval from the United States Food and Drug Administration (FDA) of KIMMTRAK® (tebentafusp-tebn) for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM). Tebentafusp (IMCgp100) is a bispecific fusion protein composed of: 1) a T cell receptor (TCR) recognizing a human leukocyte antigen (HLA)-A*02:01 complexed with a peptide derived from gp100 antigen expressed by melanoma cells, and 2) an antibody single-chain variable fragment that binds CD3 present on T cells. Developed by Immunocore, this molecule creates a bridge between tumor cells and immune cells, and thus facilitates tumor-cell killing by T cells. As the TCR domain recognizes a peptide presented on HLA-A*02:01, tebentafusp can only be used to treated patients expressing this HLA type. Tebentafusp has been granted Breakthrough Therapy, Fast Track, and Orphan Drug designations by the FDA.

The marketing applications are based on a late-stage clinical trial (NCT03070392) that enrolled 378 patients with advanced uveal melanoma who were HLA-A*0201–positive. In the study, patients were randomized 2:1 to receive tebentafusp or investigator’s choice of therapy (either pembrolizumab, ipilimumab, or dacarbazine). Tebentafusp was administered at a dose of 20 micrograms on cycle 1 Day 1, then 30 micrograms on cycle 1 Day 8, then 68 micrograms on cycle 1 Day 15 and weekly thereafter by IV infusion over 15 minutes until confirmed disease progression or unacceptable toxicity. The primary outcome measure is overall survival. As reported in September 2021, the OS Hazard Ratio in the intent-to-treat population favored KIMMTRAK, HR=0.51 (95% CI: 0.37, 0.71); p< 0.0001, over investigator’s choice (82% pembrolizumab; 13% ipilimumab; 6% dacarbazine). Moreover, the 1-year survival rate was 73% for patients in the experimental arm vs. 59% in the investigator’s choice arm.

The European Medicines Agency, the United Kingdom’s Medicines and Healthcare Regulatory Agency, Health Canada, and the Australian Government Department of Health Therapeutic Goods Administration have accepted the submission of Marketing Authorisation Applications for tebentafusp.

KIMMTRAK is the 1st antibody-based therapeutic granted a first approval for marketing in the EU or US in 2022. Explore our searchable table of antibody therapeutics approved in the EU or US for details.

“Antibodies to Watch in 2022” is now online!

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In this 13th installment of the annual ‘Antibodies to Watch’ article series, we discuss key events in commercial antibody therapeutics development that occurred in 2021 and forecast events that might occur in 2022. Regulatory review of antibody therapeutics that target the SARS-CoV-2 coronavirus proceeded at an unprecedented pace in 2021, resulting in both emergency use authorizations and full approvals for sotrovimab, regdanvimab, REGEN-COV2, as well as others, in numerous countries. As of November 1, a total of 11 antibody therapeutics had been granted first approvals in either the United States or European Union in 2021 (evinacumab, dostarlimab loncastuximab tesirine, amivantamab, aducanumab, tralokinumab, anifrolumab, bimekizumab, tisotumab vedotin, regdanvimab, REGEN-COV2). The first global approvals of seven products, however, were granted elsewhere, including Japan (pabinafusp alfa), China (disitamab vedotin, penpulimab, zimberelimab), Australia (sotrovimab, REGEN-COV2), or the Republic of Korea (regdanvimab).

Globally, at least 27 novel antibody therapeutics are undergoing review by regulatory agencies. First actions by the Food and Drug Administration on the biologics license applications for faricimab, sutimlimab, tebentafusp, relatlimab, sintilimab, ublituximab and tezepelumab are expected in the first quarter of 2022. Finally, our data show that, with antibodies for COVID-19 excluded, the late-stage commercial clinical pipeline of antibody therapeutics grew by over 30% in the past year. Of those in late-stage development, marketing applications for at least 22 may occur by the end of 2022.

The full article can be viewed and downloaded here.

Don’t miss the Supplemental Tables, which include data for 115 antibody therapeutics in late-stage clinical studies!

FDA approves Solensia (frunevetmab) for osteoarthritis pain in cats

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On January 13, 2022, the U.S. Food and Drug Administration (FDA) approved Solensia (frunevetmab), the first monoclonal antibody (mAb) new animal drug approved by the FDA for use in any animal species. Solensia™ is approved for the control of pain associated with osteoarthritis in cats.

Developed by Zoetis Inc., frunevetmab is a felinized immunoglobulin G mAb that targets nerve growth factor. Similar to humanization, felinization is a process in which all regions of a murine antibody are replaced with feline counterparts except for the complementarity-determining regions. Substantial evidence of effectiveness was demonstrated by the results of two field studies in cats with naturally occurring osteoarthritis. The endpoints used to evaluate the effectiveness of Solensia™ were observer-reported measures conducted by either owners (assessment of the cat’s activities before development of osteoarthritis, as well as before and after treatment) or veterinarians (orthopedic examinations before and after treatment).

Solensia™ is given by subcutaneous injection once a month and is dosed by weight range. Cats are given the full contents of 1 or 2 vials based on body weight to target a minimum dose of 1 mg/kg. Each vial contains 7 mg of frunevetmab.

At least one other mAb, lokivetmab (Cytopoint), is approved for veterinarian use in the US.  Manufactured by Zoetis, the product is used to treat atopic dermatitis in dogs, but it was approved by the US Department of Agriculture, not FDA. More information on FDA’s Center for Veterinary Medicine and the New Animal Drug Application (NADA) process can be found here.