Food and Drug Administration Archives

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.

FDA approves mirvetuximab soravtansine for ovarian, fallopian tube, or primary peritoneal cancer

November 15, 2022 by Janice Reichert

The US Food and Drug Administration (FDA) granted an accelerated approval for mirvetuximab soravtansine-gynx (ELAHERE™) for the treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens, on November 14, 2022. FDA also approved a companion diagnostic, VENTANA FOLR1 (FOLR1-2.1) RxDx Assay, developed by Roche.

Mirvetuximab soravtansine, developed by ImmunoGen as a treatment for epithelial malignancies such as ovarian adenocarcinoma, is an antibody-drug conjugate (ADC) targeting folate receptor alpha (FRα). The cytotoxic warhead, the tubulin-targeting maytansinoid drug DM4, is conjugated to the humanized IgG1ҡ antibody via a cleavable disulfide linker. The ADC has been granted Orphan Drug designations for ovarian cancer in the US and EU, and FDA’s Fast Track designation for a specific subset of ovarian cancer patients with medium to high FRα-positive platinum-resistant lesions who received between one and three prior systemic treatments, and for whom single-agent chemotherapy is appropriate as the next line of therapy.

FDA’s approval was based on positive results of the Phase 3 SORAYA study (NCT04296890), which evaluated the efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant advanced high-grade epithelial ovarian, primary peritoneal or fallopian tube cancer, whose tumors express a high-level of FRα. A total of 106 platinum-resistant ovarian cancer patients with high FRα expression previously treated with at least one, but less than three prior systemic treatments, at least one of which included bevacizumab, received mirvetuximab soravtansine (6 mg/kg adjusted ideal body weight) administered on day 1 of every 3-week cycle. Results from the SORAYA trial were presented at the Society of Gynecologic Oncology (SGO) annual meeting held in March 2022. Additional efficacy analyses based on a 120-day cut-off date showing tumor reduction in 71.4% of patients, an objective response rate of 32.4% as assessed by the investigator, and a preliminary median OS of 13.8 months were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting held June 3-7, 2022. A retrospective safety analysis based on 464 patients with FRα positive, recurrent ovarian cancer pooled across three studies (a Phase 1 first-in-human trial and the Phase 3 FORWARD I and SORAYA trials) demonstrating a differentiated and consistent safety profile was also presented at the 2022 ASCO meeting.

Mirvetuximab soravtansine was also evaluated in the randomized Phase 3 FORWARD I trial (NCT02631876), which enrolled 366 patients with platinum-resistant ovarian cancer, randomized 2:1 to receive either the ADC or the physician’s choice of pegylated liposomal doxorubicin, topotecan, or weekly paclitaxel. Improved patient-reported outcomes associated with mirvetuximab compared with chemotherapy were presented at the European Society for Medical Oncology (ESMO) in held in Paris, France in September 2022. In addition, ImmunoGen continues to enroll patients in the randomized, open-label Phase 3 MIRASOL study (NCT04209855), which is evaluating mirvetuximab soravtansine vs. investigator’s choice of chemotherapy in platinum-resistant, advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha expression. Top-line data from the confirmatory MIRASOL study are expected to be announced in early 2023. If positive, the results may support a full approval by FDA.

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

FDA approves teclistamab (Tecvayli) for relapsed or refractory multiple myeloma

October 26, 2022 by Janice Reichert

On October 25, 2022, the Food and Drug Administration granted accelerated approval to teclistamab-cqyv (Tecvayli, Janssen Biotech, Inc.) for adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Teclistamab (TECVAYLI) is a T-cell redirecting IgG4λ bispecific antibody recognizing BCMA on target cells and CD3e on T cells. Generated from Ligand’s transgenic mouse (OmniAb) and Genmab’s DuoBody technology, the Fc was engineered with the stabilizing S228P mutation and L234A/L235A mutations to minimize its effector functions. Teclistamab was granted Orphan Drug designations for the treatment of MM in both the US and EU, and received the Breakthrough Therapy designation for the treatment of relapsed or refractory MM (RRMM) by the FDA, and a PRIority MEdicines (PRIME) designation by the EMA for treatment of adult patients with RRMM who previously received ≥3 prior lines of therapy. TECVAYLI (teclistamab) was granted conditional marketing authorization in the EU as monotherapy for the treatment of adult RRMM patients who previously received ≥3 prior lines of therapy in August 2022.

The authorizations for marketing were based on the results from the multicohort, open-label, Phase 1 and Phase 2 MajesTEC-1 studies (NCT03145181, NCT04557098, respectively), evaluating the safety and efficacy of teclistamab in adults with RRMM. The ongoing first-in-human dose escalation and dose expansion clinical study (NCT03145181) is assessing the efficacy of teclistamab in patients with RRMM, with the antibody administered IV (range: 0.3−19.2 μg/kg [once every 2 weeks] or 19.2−720 μg/kg [once per week]) or subcutaneously (range: 80−3000 μg/kg [once per week]) in different cohorts, with step-up dosing for 38.4 μg/kg or higher doses. Based on the dose escalation data, in the Phase 2 portion of the study patients received a weekly subcutaneous dose of teclistamab (1.5 mg/kg), after receiving step-up doses of 0.06 mg/kg and 0.3 mg/kg. Results of the MajesTEC-1 study showed that teclistamab induced durable responses that deepened over time in patients with triple-class exposed RRMM (n=165), with an overall response rate of 63%, including a complete response in 39.4% of the patients. The median duration of response and duration of progression-free survival were 18.4 months (95% confidence interval [CI], 14.9 to not estimable) and 11.3 months (95% CI, 8.8 to 17.1), respectively. Adverse events were consistent with this patient population and toxicities consistent with T-cell redirection were mostly Grade 1/2.