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First approval for tildrakizumab-asmn

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On March 20, 2018, the US Food and Drug Administration (FDA) approved tildrakizumab-asmn (Ilumya) for treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Tildrakizumab, a humanized IgG1 kappa monoclonal antibody, targets IL-23p19 and blocks the interaction of IL-23 with its receptor, thereby inhibiting release of pro-inflammatory cytokines and chemokines.

FDA approval was supported by results from two Phase 3 trials (reSURFACE 1 and 2) in which patients were randomized to tildrakizumab 200 mg, tildrakizumab 100 mg, or placebo (2:2:1; reSURFACE 1), or to tildrakizumab 200 mg, tildrakizumab 100 mg, placebo, or etanercept 50 mg (2:2:1:2; reSURFACE 2). In these trials, the tildrakizumab 200 mg and 100 mg doses were well tolerated and found to be efficacious compared with placebo and etanercept in the treatment of patients with moderate-to-severe chronic plaque psoriasis. The results of both studies were published in The Lancet in July 2017.

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. As of March 23, a total of 3 antibody therapeutics had been granted first approvals in either the US or EU in 2018, and marketing applications for another 8 that have not yet been approved in either the EU or US are undergoing review in these regions. Please log in to access the table, located in the Members Only section.

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First approval for ibalizumab-uiyk

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On March 6, 2018, the US Food and Drug Administration (FDA) approved ibalizumab-uiyk (Trogarzo) for adult patients infected with human immunodeficiency virus (HIV) who were previously treated with multiple HIV medications and whose HIV infections are resistant currently available therapies. Ibalizumab-uiyk, a humanized IgG4 monoclonal antibody, is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. The marketing application was granted Breakthrough Therapy, Fast Track and Priority Review designations, and ibalizumab was granted an orphan drug designation by FDA. Theratechnologies Inc. and TaiMed Biologics, Inc. have an agreement to market and distribute Trogarzo in the US and Canada.

The product is administered intravenously (IV) as a single loading dose of 2,000 mg followed by a maintenance dose of 800 mg every 2 weeks after dilution in 250 mL of 0.9% sodium chloride. The safety and efficacy of ibalizumab-uiyk were evaluated in the Phase 3 TMB-301 study (NCT02475629), which was a single arm, multicenter clinical trial conducted in 40 heavily treatment-experienced HIV-infected patients with multidrug resistant HIV-1. At Week 25, viral load <50 was achieved in 43% of patients, while 55% and 48% of patients had a ≥ 1 log10 reduction in viral load and a ≥ 2 log10 reduction in viral load, respectively. The most common adverse reactions reported in at least 5% of subjects were diarrhea, dizziness, nausea, and rash. In total, 292 patients with HIV-1 infection were exposed to ibalizumab-uiyk IV infusion during clinical studies. Additional prescribing information for the drug can be found here.

The Antibody Society maintains a comprehensive table of approved antibody therapeutics and those in regulatory review in the EU or US. As of March 7, 2018, a total of 2 mAbs have been granted first approvals in either the US or EU in 2018, and marketing applications for a total of 9 antibody therapeutics that have not yet been approved in either the EU or US are undergoing review in these regions. Please log in to access the table, located in the Members Only section.

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Antibodies new to the market, and exiting

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On February 23, 2018, Kyowa Hakko Kirin Co. Ltd and its partner Ultragenyx Pharmaceutical Inc. announced that a conditional marketing authorization had been granted in the European Union (EU) for burosumab (Crysvita) as a treatment for X-linked hypophosphatemia in children 1 year of age and older, and adolescents with growing skeletons. Burosumab is a human IgG1 monoclonal antibody that binds to and inhibits the activity of fibroblast growth factor 23, thereby reducing loss of phosphate from the kidney and other metabolic abnormalities, and ameliorating bone changes that are a hallmark of the disease. The marketing approval in the EU is the first for burosumab. A biologics license application is undergoing review by the US Food and Drug Administration (FDA), and an action on the application is expected by April 17, 2018.

On February 27, 2018, Roche announced that emicizumab (Hemlibra®) had been approved in the EU for routine prophylaxis of bleeding episodes in people with hemophilia A with factor VIII inhibitors. Emicizumab, a bispecific IgG4 mAb targeting Factors IXa and X that originated at Chugai Pharmaceutical Co. Ltd., was approved by the FDA on November 16, 2017.

On March 2, 2018, Biogen and AbbVie announced the voluntary worldwide withdrawal of marketing authorizations for ZINBRYTA® (daclizumab) for relapsing multiple sclerosis (MS). The withdrawal coincides with an urgent review by the European Medicines Agency (EMA) of inflammatory brain disorder in 8 patients, and follows a 2017 review by EMA of reports of liver injury. Due to the risk of serious liver damage, EMA limited use of Zinbryta to MS patients who had tried at least two other disease modifying treatments and could not be treated with any other such treatments. ZINBRYTA® had been marketed in the EU, US, Switzerland, Canada and Australia.

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Antibodies to watch in 2018

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The pace of antibody therapeutics development accelerated in 2017, and this faster pace is projected to continue through 2018. Notably, the annual number of antibody therapeutics granted a first approval in either the European Union (EU) or United States (US) reached double-digits (total of 10) for the first time in 2017. The 10 antibodies granted approvals are: brodalumab, dupilumab, sarilumab, guselkumab, benralizumab, ocrelizumab, inotuzumab ozogamicin, avelumab, duvalumab, and emicizumab. Brodalumab, however, had already been approved in Japan in 2016.
As of mid-December 2017, 10 antibody therapeutics (ibalizumab, burosumab, tildrakizumab, caplacizumab, erenumab, fremanezumab, galcanezumab, romosozumab, mogamulizumab, cemiplimab) were in regulatory review in the EU or US, and regulatory actions on their marketing applications are expected by the end of 2018.
Based on company announcements and estimated clinical study primary completion dates, and assuming the study results are positive, marketing applications for at least 13 antibody therapeutics that are now being evaluated in late-stage clinical studies may be submitted by the end of 2018. Of the 13 candidates, 8 are for non-cancer indications (lanadelumab, crizanlizumab, ravulizumab, eptinezumab, risankizumab, satralizumab, brolucizumab, PRO140) and 5 are for cancer (sacituzumab govitecan, moxetumomab pasudotox, cemiplimab, ublituximab, isatuximab).
Additional antibody therapeutics to watch in 2018 include 19 mAbs undergoing evaluation in late-stage studies with primary completion dates in late 2017 or during 2018. Of these mAbs, 9 are for non-cancer indications (lampalizumab, roledumab, emapalumab, fasinumab, tanezumab, etrolizumab, NEOD001, gantenerumab, anifrolumab) and 10 are for cancer indications (tremelimumab, isatuximab, BCD-100, carotuximab, camrelizumab, IBI308, glembatumumab vedotin, mirvetuximab soravtansine, oportuzumab monatox, L19IL2/L19TNF). Positive clinical study results may enable marketing application submissions in 2018. Brief summaries of these antibody therapeutics are provided in the ‘Antibodies to watch in 2018’ article, which is now available on the mAbs website. A PDF of this open-access article is available here.

Emicizumab granted FDA approval

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Emicizumab (Hemlibra, emicizumab-kxwh, ACE910, RO5534262), a bispecific IgG4 mAb targeting Factors IXa and X, was approved by the FDA on November 16, 2017. The drug, which is administered once a week, was approved to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients with hemophilia A who have developed Factor VIII inhibitors. The biologics license application was granted Priority Review and a Breakthrough Therapy designation. Hemlibra was also granted an orphan drug designation by the FDA.

Marketing applications for emicizumab are under review in the European Union and Japan; the European Medicines Agency is reviewing the marketing authorization application under accelerated assessment. Emicizumab was granted an orphan drug designation in Japan for the prevention and reduction of bleeding episodes in patients with congenital factor VIII deficiency with inhibitors. The drug was created by Chugai Pharmaceutical Co., Ltd. and co-developed by Chugai, Roche and Genentech.

The marketing applications for emicizumab include results from the Phase 3 HAVEN 1 (NCT02622321) study and interim analysis of the HAVEN 2 (NCT02795767) study. In the HAVEN 1 study, adult and adolescent patients (12 or older) who had previously received episodic treatment with bypassing agents were randomly assigned in a 2:1 ratio to emicizumab prophylaxis (group A) or no prophylaxis (group B). The primary end point of the study was the difference in bleeding rates between Group A and Group B. Emicizumab was administered subcutaneously at a dose of 3 milligrams per kilogram per week (mg/kg/week) for 4 weeks followed by 1.5 mg/kg/week up to the end of the study. The annualized bleeding rate in Group A was reduced by 87% compared to Group B (2.9 events vs 23.3 events, P<0.001). [1] The HAVEN 2 study is evaluating the efficacy, safety, and pharmacokinetics of subcutaneous administration of emicizumab in hemophilia A pediatric patients with inhibitors.

1. Oldenburg J, Mahlangu JN, Kim B, Schmitt C, Callaghan MU, Young G, Santagostino E, Kruse-Jarres R, Negrier C, Kessler C, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. 2017;377(9):809-818. doi: 10.1056/NEJMoa1703068.

The Antibody Society maintains a comprehensive table of approved antibody therapeutics and those in regulatory review in the EU or US. As of November 16, 2017, a total of 10 mAbs have been granted first approvals in either the US or EU in 2017, and marketing applications for a total of 9 antibody therapeutics that have not yet been approved in either the EU or US are undergoing review in these regions.

Please log in to access the table, located in the Members Only section.

Not a member? Please join! Membership is free for students and employees of the Society’s corporate sponsors.