Food and Drug Administration Archives

FDA approves bispecific antibody EPKINLY™ (epcoritamab-bysp)

May 19, 2023 by Janice Reichert

On May 19, 2023, the US Food and Drug Administration approved EPKINLY™ (epcoritamab-bysp) for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B‑cell lymphoma, after two or more lines of systemic therapy. Created using Genmab’s DuoBody® technology, epcoritamab (GEN3013, DuoBody®-CD3xCD20) is a T cell-engaging bispecific IgG1k/l antibody targeting CD20 and CD3 that is jointly owned by Genmab and AbbVie. EPKINLY was approved under FDA’s accelerated approval program based on response rate and durability of response. Continued approval for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial(s).

FDA’s approval was supported by data from the pivotal Phase 1/2 EPCORE NHL-1 trial (NCT03625037) studying epcoritamab in 157 patients with relapsed or refractory large B-cell lymphoma who had received at least two prior systemic therapies, including some who had received prior treatments with CAR-T cell therapy. The dose escalation findings from the Phase 1 part identified a dose of 48 mg as the recommended Phase 2 dose. In the Phase 2 part, patients received 48 mg of epcoritamab as 1 ml subcutaneous injections in 28-day cycles, with weekly dosing in Cycles 1-2, dosing every second week in Cycles 3-6, and dosing every 4 weeks from Cycle 7 onward. An overall response (complete or partial response) was seen in 61% (90/148 [95 percent confidence interval (CI): 52.5-68.7]) of patients and 38% (56/148 [95 percent CI: 30.0-46.2]) achieved complete remission. The median duration of response was 15.6 months (95 percent CI: 9.7-Not reached).

Epcoritamab is being investigated in multiple ongoing clinical studies across different settings and histologies. The most advanced of these is the randomized, open-label Phase 3 EPCORE™DLBCL-1 trial (NCT04628494) of epcoritamab vs investigator’s choice chemotherapy in patients with R/R DLBCL. The study is recruiting an estimated 552 patients and has an estimated primary completion date in June 2024.

Interested in data for other antibody therapeutics that have received marketing authorizations? Go to our searchable table of approved antibody therapeutics and those in regulatory review for more information.

FDA approves Zynyz™ (retifanlimab-dlwr) for Merkel cell carcinoma

March 23, 2023 by Janice Reichert

On March 22, 2023, the US Food and Drug Administration approved Zynyz™ (retifanlimab-dlwr) for the treatment of adults with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC). Retifanlimab (INCMGA00012, MGA012) is a humanized, hinge-stabilized IgG4k antibody targeting PD-1. The biologics license application for Zynyz for MCC was approved under accelerated approval based on tumor response rate and duration of response.

FDA’s approval was based on data from the Phase 2 POD1UM-201 trial (NCT03599713), an open-label, multiregional, single-arm study that evaluated Zynyz in adults with metastatic or recurrent locally advanced MCC who had not received prior systemic therapy for their advanced disease. In this study, patients received Zynyz 500 mg intravenously every four weeks until disease progression, unacceptable toxicity, for up to 24 months. The primary endpoint was objective response rate (ORR) as determined by independent central radiographic review using RECIST v1.1. Secondary endpoints included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Among chemotherapy-naïve patients (n=65), Zynyz monotherapy resulted in an ORR of 52% (95% confidence interval [CI]: 40-65). Complete response was seen in 12 patients (18%), and 22 patients (34%) showed partial response. Among the responding patients, the DOR ranged from 1.1 to 24.9+ months; 76% (26/34) experienced a DOR of six months or longer and 62% (21/34) experienced a DOR of 12 months or longer by landmark analysis.

Incyte Corporation, which licensed retifanlimab from MacroGenics in 2017, is sponsoring clinical studies evaluating retifanlimab monotherapy as a treatment for other cancers, including endometrial cancer, non-small cell lung cancer, and squamous cell carcinoma of the anal canal.

FDA approves Leqembi (lecanemab-irmb) for the treatment of Alzheimer’s disease

January 6, 2023 by Janice Reichert

On January 6, 2023, the U.S. Food and Drug Administration approved Leqembi (lecanemab-irmb) via the Accelerated Approval pathway for the treatment of Alzheimer’s disease. The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials. The approved dose of lecanemab is 10 milligram/kilogram every two weeks.

Lecanemab (BAN2401) is a humanized anti-amyloid beta protofibril IgG1k antibody initially developed by BioArctic Neuroscience. BAN2401 was licensed to Eisai in a collaboration agreement, allowing the jointly development of lecanemab as a treatment for Alzheimer disease (AD). Under an agreement with Biogen, Eisai and Biogen co-commercialize and co-promote lecanemab.

The accelerated approval was supported by data from Study 201 (NCT01767311), which assessed the clinical efficacy of lecanemab at multiple doses (2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly, 10 mg/kg biweekly) or placebo and explored the dose response of lecanemab using a composite clinical score (ADCOMS) in 856 patients with mild cognitive impairment due to AD and mild AD with confirmed presence of amyloid pathology. Patients receiving the treatment had significant dose- and time-dependent reduction of amyloid beta plaque, with patients receiving the approved dose of lecanemab, 10 milligram/kilogram every two weeks, having a statistically significant reduction in brain amyloid plaque from baseline to Week 79 compared to the placebo arm, which had no reduction of amyloid beta plaque.

Lecanemab is also being evaluated in the Clarity AD Phase 3 study (NCT03887455), which is designed to evaluate the efficacy, long-term safety, and tolerability of 10 mg/kg IV lecanemab administered every 2 weeks in 1795 patients with early AD. The primary outcome measurement was the change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 18 months of treatment. In September 2022, Eisai Co and Biogen Inc announced positive topline results from Clarity AD Phase 3 trial where lecanemab met the primary endpoint by reducing by 27% the clinical decline on the CDR-SB compared with placebo at 18 months. All key secondary endpoints were also met. Based on results of the study, Eisai may file for traditional approval in the US and for marketing authorization applications in Japan and Europe.

Ublituximab approved by FDA for multiple sclerosis

December 28, 2022 by Janice Reichert

On December 28, 2022, the U.S. Food and Drug Administration approved BRIUMVI™ (ublituximab-xiiy), for the treatment of relapsing forms of multiple sclerosis (RMS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. [1]

Ublituximab (TG-1101) is a chimeric anti-CD20 IgG1k antibody glycoengineered for enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) that was originally developed by LFB Biotechnology and licensed to TG Therapeutics as a treatment for CLL and multiple sclerosis (MS).

The approval was based on results of the randomized, double-blinded, active-controlled Phase 3 trials ULTIMATE I (NCT03277261) and ULTIMATE II (NCT03277248) evaluating ublituximab (450 mg dose IV every 6 months, following a Day 1 infusion of 150 mg over four hours and a Day 15 infusion over one hour) compared to teriflunomide (14 mg oral tablets taken once daily) in a total of 1,094 patients with relapsing MS for both studies. The primary endpoint was the annualized relapse rate (ARR). Results from the ULTIMATE I and II Phase 3 trials showed that the primary endpoint was met, with a significant reduction of the ARR for ublituximab vs. teriflunomide over a period of 96 weeks. [2]

1. TG Therapeutics, Inc. TG Therapeutics Announces FDA Approval of BRIUMVI™ (ublituximab-xiiy). Dec 28, 2022 press release

2. Steinman L, Fox E, Hartung HP, Alvarez E, Qian P, Wray S, Robertson D, Huang D, Selmaj K, Wynn D, et al. Ublituximab versus teriflunomide in relapsing multiple sclerosis. N Engl J Med. 2022;387(8):704-714. doi:10.1056/NEJMoa2201904.

FDA approves TZIELD™ (teplizumab-mzwv) to delay the onset of Stage 3 type 1 diabetes

November 18, 2022 by Janice Reichert

On November 17, 2022, the US Food and Drug Administration (FDA) approved TZIELD™ (teplizumab-mzwv) to delay the onset of Stage 3 type 1 diabetes (T1D) in adult and pediatric patients aged 8 years and older with Stage 2 T1D. The approval was based in part on a clinical trial in Stage 2 T1D patients in which TZIELD delayed the median onset of Stage 3 T1D by 25 months, or approximately 2 years, compared to placebo.

Teplizumab is a humanized, anti-CD3e IgG1k antibody originally developed at Tolerance Therapeutics, Inc. and the University of California. The antibody Fc region was mutated (L234A; L235A) to reduce effector functions. Teplizumab binds CD3 expressed on mature T cells and may induce expansion and/or regulatory function in T cell subsets. In 2005, teplizumab was licensed to MacroGenics. In 2018, Provention Bio acquired all rights to teplizumab and subsequently continued its development for the prevention and treatment on T1D. The FDA granted teplizumab Orphan Drug designation for the treatment of recent-onset T1D. Teplizumab was also granted FDA’s Breakthrough Therapy designation for the prevention or delay of clinical T1D in at-risk individuals and EMA’s PRIority MEdicines (PRIME) designation for the same indication. As of October 2022, Provention Bio and Sanofi had entered into a co-promotion agreement for teplizumab.

Provention Bio is currently evaluating teplizumab in patients with newly diagnosed insulin-dependent T1D in the global PROTECT (PROvention T1D trial Evaluating C-peptide with Teplizumab) Phase 3 study (NCT03875729). This randomized, double-blind, placebo-controlled, multicenter trial will enroll 300 patients with recent onset T1D who will be randomized 2:1 to either two 12-day cycles of teplizumab (IV) or placebo. The primary efficacy endpoint is C-peptide change. Secondary endpoints include insulin use, HbA1c, hypoglycemic episodes, and safety. The company expects top line data from PROTECT Phase 3 study in 2H 2023.

Interested in more information about approved antibody therapeutics? Explore our searchable table of antibody therapeutic products for details.