Food and Drug Administration Archives

What are the “Antibodies to Watch” in 2022? Find out on Dec 2nd!

November 29, 2021 by Janice Reichert

Join us for our next webinar, December 2, 2021, at 11am ET / 5pm CET

In “Antibodies to Watch in 2022”, Drs. Janice Reichert, Alicia Chenoweth and Silvia Crescioli will discuss key events in antibody therapeutics development that occurred in 2021 and forecast events that might occur in 2022. The COVID-19 pandemic continued to pose challenges and opportunities to the healthcare system, but companies forged ahead with development plans, resulting in record numbers of antibody therapeutics in late-stage clinical studies and in regulatory review. Globally, regulatory agencies approved a record number of novel antibody-based products, including anti-SARS-CoV-2 antibodies. The speakers will provide details of 2021 events and trends in the development of antibody therapeutics projected for 2022.

Registration is open!

Tisotumab vedotin approved by FDA for cervical cancer

September 21, 2021 by Janice Reichert

On September 20, 2021, FDA granted accelerated approval to TIVDAK (tisotumab vedotin-tftv) for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. The BLA for TIVDAK for this indication was given a Priority review. TIVDAK’s approval was based on tumor response and the durability of the response; verification and description of clinical benefit in confirmatory trials may be necessary for continued approval for this indication.

TIVDAK is an ADC comprising Genmab’s human tissue factor IgG1k antibody targeting tissue factor conjugated to MMAE via a protease-cleavable linker using Seagen’s ADC technology. The companies are co-developing the product. The recommended dose of TIVDAK is 2 mg/kg (up to a maximum of 200 mg) given as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity.

FDA’s approval was based on results of the pivotal single-arm Phase 2 innovaTV 204 study (NCT03438396), which included 101 patients with recurrent or metastatic cervical cancer who had received no more than two prior systemic regimens in the recurrent or metastatic setting, including at least one prior platinum-based chemotherapy regimen. Patients received tisotumab vedotin 2.0 mg/kg IV every 3 weeks until progression or toxicity. The major efficacy outcome measures were confirmed objective response rate as assessed by an independent review committee using RECIST v1.1 criteria and duration of response (DOR). The objective response rate was 24% [95% CI: 15.9%-33.3%], including 7 patients (7%) with a complete response and 17 patients (17%) with a partial response, and the median DOR was 8.3 months (95% CI: 4.2, not reached).

TIVDAK is the 9th antibody therapeutic to be first approved for marketing in the EU or US in 2021. Explore our searchable table of antibody therapeutics approved in the US or EU for details.

FDA issues Complete Response Letter for oportuzumab monatox BLA

August 26, 2021 by Janice Reichert

Oportuzumab monatox (Vysyneum™, Vicineum®, VB4-845) is a humanized single-chain variable fragment (scFv) targeting epithelial cell adhesion molecule fused to Pseudomonas aeruginosa exotoxin A (ETA(252-608). Sesen Bio is developing the drug, administered intravesically or intratumorally, as a treatment of high-risk non-muscle invasive bladder cancer (NMIBC) that is unresponsive to treatment with bacillus Calmette-Guérin (BCG). Oportuzumab monatox was granted FDA’s Fast Track designation for the treatment of NMIBC.

Sesen Bio’s rolling BLA submission for oportuzumab monatox for the treatment of BCG-unresponsive NMIBC was completed in December 2020, and accepted by FDA and granted Priority Review in February 2021. On August 13, 2021, the company announced that it received a Complete Response letter from the FDA in which the agency provided recommendations specific to additional clinical and statistical data and analyses, as well as Chemistry, Manufacturing and Controls (CMC) issues. Sesen Bio plans to work with FDA to address the concerns expressed in the letter. If another clinical trial is required, the company projects resubmitting the BLA in 2023. [1]

Sesen Bio submitted an MAA to the EMA for oportuzumab monatox for the treatment of high-risk, BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) in March 2021, but withdrew the application in August 2021. [2]

FDA approves anifrolumab for systemic lupus erythematosus

August 3, 2021 by Janice Reichert

On July 30, 2021, the US Food and Drug Administration approved AstraZeneca’s Saphnelo (anifrolumab-fnia) for the treatment of adult patients with moderate to severe systemic lupus erythematosus (SLE) who are receiving standard therapy. The recommended dosage is 300 mg administered as an intravenous infusion over a 30-minute period every 4 weeks. Saphnelo is undergoing regulatory review for SLE in the EU and Japan.

Anifrolumab (MEDI-546) is an interferon (IFN) alpha receptor 1 (IFNAR1)-specific human IgG1κ antibody. It binds to subunit 1 of IFNAR1, thereby blocking the action of different type I IFNs (IFN-α, IFN-β and IFN-ω). The heavy chain of the antibody incorporates 3 mutations, L234F, L235E, and P331S, to decrease effector functions. Type I IFNs are involved in the pathogenesis of SLE, and ~ 60-80% of adult patients with active SLE express elevated levels of type I IFN-inducible genes.

FDA’s approval was based in part on efficacy and safety data from two TULIP Phase 3 trials and the MUSE Phase 2 trial. In these trials, more patients treated with Saphnelo experienced a reduction in overall disease activity across organ systems, including skin and joints, and achieved sustained reduction in oral corticosteroid use compared to placebo, with both groups receiving standard therapy. Clinical study results from the Phase 3 TULIP-2 and TULIP-1 trials were published in The New England Journal of Medicine and in The Lancet Rheumatology, respectively, while results from the MUSE Phase 2 trial were published in Arthritis & Rheumatology.

Need help keeping up to date on US and EU approvals?

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US in the Web Resources section of our website.

FDA issues a complete response letter for retifanlimab’s BLA

July 25, 2021 by Janice Reichert

On July 23, 2021, Incyte Corporation announced that the U.S. Food and Drug Administration (FDA) issued a Complete Response letter regarding its Biologics License Application (BLA) for retifanlimab (formerly INCMGA00012, MGA012) for the treatment of adult patients with locally advanced or metastatic squamous cell carcinoma of the anal canal (SCAC) who have progressed on, or who are intolerant of, platinum-based chemotherapy. Retifanlimab, which is a humanized, hinge-stabilized IgG4κ monoclonal antibody targeting programmed cell death protein 1 (PD-1), was granted FDA’s Fast track and Orphan Drug designations for the treatment of anal cancer.

The BLA submission was based on data from the Phase 2 POD1UM-202 trial (NCT03597295) evaluating retifanlimab in previously treated patients with locally advanced or metastatic SCAC who have progressed on, or were ineligible for or intolerant of, platinum-based chemotherapy. The objective response rate was 13.8% (95% confidence interval [Cl]: 7.6, 22.5) based on confirmed tumor responses by independent central radiographic review. Twelve patients (12.8%) had partial responses, 1 patient (1.1 %) had a complete response and 33 (35.1%) had stable disease. On June 24, 2021, FDA’s Oncologic Drug Advisory Committee had voted 13 to 4 for the deferral of the FDA approval of retifanlimab. FDA’s letter indicates that the application cannot be approved in its present form and additional data are needed to demonstrate the clinical benefit of retifanlimab for the treatment of patients with advanced or metastatic SCAC.

In addition to SCAC, retifanlimab is also currently under evaluation as a monotherapy for patients with microsatellite instability-high endometrial cancer, and Merkel cell carcinoma; and in combination with platinum-based chemotherapy for patients with non-small cell lung cancer. Incyte has an exclusive collaboration and license agreement with MacroGenics, Inc. for global rights to retifanlimab and a collaboration and license agreement with Zai Lab for the development and commercialization of retifanlimab in Greater China.

Need help keeping up to date on US and EU approvals?

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US in the Web Resources section of our website.