Food and Drug Administration Archives

FDA approves anti-LAG-3 relatlimab-rmbw as part of a combination therapy for melanoma

March 19, 2022 by Janice Reichert

On March 18, 2022, Bristol Myers Squibb announced that Opdualag a fixed-dose combination of anti-PD-1 nivolumab and relatlimab-rmbw, administered as a single intravenous infusion, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult and pediatric patients 12 years of age or older with unresectable or metastatic melanoma.

Relatlimab (BMS-986016, ONO4482) is a human IgG4k antibody that targets LAG-3, which, like PD-1, is an immune checkpoint. Bristol Myers Squibb and Ono have a strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea, and Taiwan. An marketing authorization application is undergoing evaluation by the European Medicines Agency.

FDA’s approval was based on data from the Phase 2/3 RELATIVITY-047 trial (NCT03470922), which evaluated the effects of relatlimab combined with nivolumab versus nivolumab in a total of 714 patients with previously untreated metastatic or unresectable melanoma. Patients were randomized 1:1 and administered a fixed-dose combination of 160 mg relatlimab and 480 mg nivolumab or 480 mg nivolumab by intravenous infusion every 4 weeks until disease recurrence, unacceptable toxicity or withdrawal of consent. The study’s primary endpoint, progression-free survival (PFS) by blinded independent central review, was met. The median PFS in the group that received both relatlimab and nivolumab (n=355) was significantly longer (10.1 months [95% CI, 6.4–15.7]) than in the group that received nivolumab only (4.6 months [95% CI, 3.4–5.6]; hazard ratio: 0.75 [95% CI, 0.6–0.9]; P = 0.0055). [1]

1. Tawbi HA, Schadendorf D, Lipson EJ, et al. Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma. N Engl J Med. 2022;386:24-34.

Opdualag is the 4th 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.

FDA issues emergency use authorization for bebtelovimab

February 11, 2022 by Janice Reichert

On February 11, 2022, the U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for bebtelovimab (LY-CoV1404), an anti-SARS-CoV-2 monoclonal antibody that demonstrates neutralization against the Omicron variant. Bebtelovimab targets the SARS-CoV-2 spike glycoprotein receptor binding domain. The EUA was issued to Eli Lilly and Co.

The EUA for bebtelovimab is supported by clinical and nonclinical data. The clinical data are from a Phase 2, randomized, single-dose clinical trial (NCT04634409) evaluating the efficacy of bebtelovimab alone and bebtelovimab combined with other monoclonal antibodies for treating mild to moderate COVID-19.

Bebtelovimab is authorized for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate. The authorized dose of bebtelovimab is 175 mg given as an intravenous injection over at least 30 seconds. A fact sheet for health care providers with additional information about bebtelovimab can be found here.

As previously announced, Lilly signed an agreement with the U.S. government to supply up to 600,000 doses of investigational drug bebtelovimab for at least $720 million.

FDA approves Enjaymo (sutimlimab-jome) for cold agglutinin disease

February 5, 2022 by Janice Reichert

On February 4, 2022, the US Food and Drug Administration (FDA) approved Enjaymo (sutimlimab-jome) infusion to decrease the need for red blood cell transfusion due to hemolysis in adults with cold agglutinin disease (CAD). This rare autoimmune disorder is characterized by hemolysis caused by activation of the classic complement pathway. Sponsored by Sanofi, sutimlimab is a hinge-stabilized, humanized IgG4k antibody that targets and inhibits complement component 1s (C1s). A mutation in the Fc region (L235E) reduces the effector functions of the antibody. Sutimlimab received FDA’s Breakthrough Therapy and Orphan Drug designations for CAD, and Orphan Drug designation in the EU for this indication.

The BLA was based on data from the CARDINAL open-label, single-arm study (NCT03347396), which enrolled 24 adult patients with CAD who received a recent blood transfusion. All participants received Enjaymo for up to six months and could choose to continue therapy in a second part of the trial. Based on body weight, participants received either a 6.5 g or 7.5 g infusion of Enjaymo on day 0, day 7, and every 14 days through week 25. In total, 54% of participants responded to Enjaymo. In this study, sutimlimab administration rapidly halted hemolysis, increased hemoglobin levels, and reduced fatigue.

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

Enjaymo is the 3rd 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.

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

January 29, 2022 by Janice Reichert

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.

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

January 26, 2022 by Janice Reichert

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.