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Tisotumab vedotin approved by FDA for cervical cancer

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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 approves anifrolumab for systemic lupus erythematosus

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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

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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.

FDA issues a complete response letter for teplizumab BLA

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Provention Bio, Inc. has announced that the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter relating to the company’s biologics license application (BLA) for teplizumab for the delay of clinical type 1 diabetes (T1D) in at-risk individuals. In the letter, the FDA stated that a single, low-dose pharmacokinetic/pharmacodynamic (PK/PD) bridging study in healthy volunteers to compare planned commercial product with drug product originating from drug substance manufactured for historic clinical trials had failed to show PK comparability. This deficiency, and others noted in the letter, will need to be suitably addressed before approval.

Teplizumab (PRV-031) is a humanized IgG1k that binds to an epitope of the CD3-epsilon chain expressed on mature T lymphocytes, and thereby modulates the pathological immunologic responses underlying T1D and other autoimmune diseases. Teplizumab was granted FDA’s Breakthrough Therapy designation for the prevention or delay of clinical T1D, and EMA granted teplizumab PRIME designation for the prevention or delay of clinical T1D in individuals at risk of developing the disease. Provention Bio acquired worldwide development and commercialization rights to teplizumab from MacroGenics, Inc. in 2018.

A rolling BLA for teplizumab for the delay or prevention of clinical Type 1 Diabetes (T1D) in at-risk individuals, as indicated by the presence of two or more T1D-related autoantibodies, was started in April 2020 and completed by November 2020. The BLA includes data from the Phase 2 “At-Risk” study (NCT01030861), which evaluated whether administration of teplizumab can prevent or delay the development of T1D in high-risk autoantibody-positive non-diabetic relatives of patients with T1D.  Participants received IV infusions of teplizumab given for 14 consecutive days (n=44) or placebo (n=32). Extended follow-up data showed that, compared to placebo, one course of teplizumab delayed insulin-dependence in presymptomatic T1D patients by a median of approximately three years. Participants in the “At-Risk” study who develop clinical type 1 diabetes after the conclusion of that trial can enroll in an extension study (NCT04270942) and receive teplizumab treatment within one year of diagnosis of clinical type 1 diabetes.

Teplizumab is also being evaluated in the Phase 3 PROTECT study (NCT03875729), which will determine whether teplizumab slows the loss of β cells and preserves β cell function in children and adolescents 8-17 years old who have been diagnosed with T1D in the previous 6 weeks. Estimated enrollment for the PROTECT study is 300 patients, and the estimated primary completion date is May 2022.

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.

Actemra® (tocilizumab) granted emergency use authorization for the treatment of COVID-19

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On June 24, 2021, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for intravenous Actemra® (tocilizumab) for the treatment of COVID-19 in hospitalized adults and pediatric patients (2 years of age and older) who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation. The EUA was issued to Genentech Inc.

Actemra is a recombinant humanized monoclonal antibody that inhibits inflammation by selectively binding to both soluble and membrane-bound human IL-6 receptors and subsequently inhibiting IL6-mediated signaling through these receptors. The data supporting Actemra’s EUA are derived from four clinical trials, the randomized, controlled, open-label, platform trial “Randomised Evaluation of COVID-19 Therapy” (RECOVERY) and three randomized, double-blind, placebo-controlled trials (EMPACTA, COVACTA and REMDACTA). The most important scientific evidence on the potential benefit of Actemra for its authorized use came from the RECOVERY and EMPACTA trials.

The EUA for Actemra is not equivalent to an approval. According to current labeling, Actemra is FDA approved for rheumatoid arthritis, giant cell arteritis, systemic sclerosis-associated interstitial lung disease, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, and cytokine release syndrome.