The Antibody Society

the official website of the antibody society

An international non-profit supporting antibody-related research and development.

First approval for risankizumab

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AbbVie has announced that SKYRIZI (risankizumab) was granted its first approval. The Japanese Ministry of Health, Labour and Welfare approved risankizumab for the treatment of plaque psoriasis, generalized pustular psoriasis, erythrodermic psoriasis and psoriatic arthritis in adult patients who have an inadequate response to conventional therapies. AbbVie is leading the development and commercialization of SKYRIZI, which is included in a collaboration with Boehringer Ingelheim.

Risankizumab is a humanized IgG1 monoclonal antibody that targets IL-23. The approval in Japan is based on efficacy and safety data from Phase 2 and Phase 3 clinical trials, sustaIMM, ultIMMa-1 and IMMspire, evaluating SKYRIZI in Japanese patients with plaque psoriasis, generalized pustular psoriasis and erythrodermic psoriasis, as well as a global Phase 2 study in patients with active psoriatic arthritis.

Marketing applications were submitted for risankizumab in both the EU and US, and regulatory decisions are anticipated in the first half of 2019. The European Medicines Agency’s Committee for Medicinal Products for Human Use has announced that it adopted a positive opinion for SKYRIZI for treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy.

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The Antibody Society maintains a comprehensive table of approved mAb therapeutics and those in regulatory review in the EU or US. Please log in to access the table, which is located in the Members Only section and can be downloaded in Excel format. Information about other antibody therapeutics that may be approved or enter regulatory review in 2019 can be found in ‘Antibodies to watch in 2019’.

BLA submission started for leronlimab as part of combination therapy for patients with HIV

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CytoDyn Inc. has submitted the non-clinical portion of a biologics license application (BLA) for leronlimab (700 mg dose) in combination with highly active antiretroviral therapy for treatment of patients with human immunodeficientcy virus (HIV).  ‘Rolling’ BLA submission is a benefit of leronlimab’s Fast Track drug designation, which was granted by the US Food and Drug Administration for this indication. CytoDyn is working to complete the clinical, and chemistry, manufacturing and controls sections of the BLA. Leronlimab, a humanized IgG4 monoclonal antibody, blocks CCR5. The chemokine receptor CCR5 is the principal HIV co-receptor, but it has potential as a drug target for other diseases, such as cancer and immune-mediated disorders.

As recently announced by CytoDyn, clinical study data has shown that a weekly dose of 525 mg and 700 mg of leronlimab yielded approximately a 90% response rate for HIV-infected patients who pass the first 10 weeks of monotherapy without virologic failure. Approximately 30% of patients fail within the first 10 weeks of monotherapy on a 525 mg dosage and 17% at a dosage of 700 mg. Patients who pass the first 10 weeks of monotherapy on a 525 mg dose have reached an average total of 32 weeks with sustained viral load suppression.

CytoDyn is also developing leronlimab as a treatment for graft-vs.-host disease (GVHD) and triple-negative breast cancer. A Phase 2 study (NCT02737306 ) of the safety and efficacy of leronlimab for prophylaxis of acute GVHD in patients undergoing reduced intensity conditioning allogeneic stem-cell transplantation has an estimated primary completion date of December 2019.  A Phase 1b/2 study (NCT03838367) of leronlimab combined with carboplatin in patients with CCR5+ metastatic triple negative breast cancer is not yet recruiting patients.

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The Antibody Society maintains a comprehensive table of approved mAb therapeutics and those in regulatory review in the EU or US. Please log in to access the table, which is located in the Members Only section and can be downloaded in Excel format. Information about other antibody therapeutics that may enter regulatory review in 2019 can be found in ‘Antibodies to watch in 2019’.

Antibody therapeutics in early-stage clinical studies

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The popular “Antibodies to watch” articles aim to update members of The Antibody Society, as well as the broader scientific community, on progress in the late-stage clinical development of innovative antibody therapeutics. Data for these molecules (60 as of March 22, 2019) are made available in the Members Only area of The Antibody Society’s website. We are pleased to announce that we are expanding our coverage of the commercial clinical pipeline to include data for antibody therapeutics that have recently entered clinical study. Two factors motivated us: 1) the remarkable increase in the number entering clinical study annually (to ~120 in 2018); and 2) the remarkable focus on antibodies developed for cancer (~80% of the total in 2018). Data for antibody therapeutics that entered clinical study recently, in Excel format, may be downloaded from the Members Only area.

The biopharmaceutical industry’s intense focus on the development of antibody therapeutics, and particularly those for cancer, is unabated in 2019, according to the data available by mid-March. We have identified 17 antibody therapeutics for which an application to start clinical study was filed or a Phase 1 study was started in 2019, and an additional 11 antibody therapeutics with clinical studies not yet recruiting patients, as listed on clinicaltrials.gov. The rate of clinical entry for antibody therapeutics so far in 2019 is thus similar to that observed in 2018 (~10 per month). The trend toward development of antibodies as treatments for cancer is also quite similar. Of the 2019 cohort so far identified, 22 of 28 (79%) are for cancer.

The commercial clinical pipeline of cancer therapies has become increasingly dominated by 3 categories of antibodies: 1) immune checkpoint modulators; 2) antibody-drug conjugates (ADCs); and 3) bispecific antibodies (see figure for details).

Our data so far suggests that this trend will continue in 2019, as nearly three-quarters of the antibody therapeutics currently in the 2019 cohort fit in one (or more) of the 3 categories. Examples of antibodies that fit more than 1 category include TG-1801 (TG Therapeutics, Inc., Novimmune SA), a bispecific antibody targeting the immune checkpoint CD47 as well as CD19, and  INBRX-105 (Inhibrx, Inc.), a bispecific antibody targeting the immune checkpoints PD-L1 and 4-1BB. TG-1801, a human IgG1 designed to target and deplete B-cells, is undergoing evaluation in a Phase 1 study (NCT03804996) of patients with B-cell lymphoma. INBRX-105 is undergoing evaluation as a treatment for hematological and solid tumors in a Phase 1 study (NCT03809624).

More to come! Throughout 2019, we will track and report on the development of all antibody therapeutics that enter clinical study during the year.

Attention members! Please log in to access our data for all antibody therapeutics that entered clinical study during 2018 or so far in 2019. After logging in, click on ‘Antibodies in early-stage studies’ in the Members Only dropdown menu. Data will be updated throughout 2019.

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Marketing application submitted for brolucizumab, an anti-VEGF-A antibody for macular degeneration

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The European Medicines Agency’s March 2019 summary of applications for new human medicines under evaluation by the Committee for Medicinal Products for Human Use indicates that an application for brolucizumab as a ophthalmological is undergoing review.

Brolucizumab, a humanized scFv that targets all isoforms of vascular endothelial growth factor-A, has been evaluated in clinical studies as a treatment for neovascular age-related macular degeneration (nAMD). In October 2018, Novartis released 96-week results from the Phase 3 HAWK (NCT02307682) and HARRIER (NCT02434328) studies that reaffirmed positive 48-week findings. The two studies included more than 1,800 patients in comparing the efficacy and safety of intravitreal injections of 6 mg brolucizumab or 3 mg brolucizumab (HAWK study only) versus 2 mg aflibercept in patients with nAMD. The primary efficacy endpoint of the studies, non-inferiority to aflibercept (EYLEA®) in mean change in best-corrected visual acuity (BCVA) at week 48, was met. The 96-week results indicate patients administered brolucizumab maintained robust visual gains, with mean change in BCVA of 5.9 letters for brolucizumab 6 mg versus 5.3 letters for aflibercept in the HAWK study, and 6.1 letters versus 6.6 letters, respectively, in the HARRIER study. Superior reductions in retinal fluid and central subfield thickness (CST) demonstrated at 48 weeks were reaffirmed at 96 weeks. The percentage of patients with nAMD that had intra-retinal fluid and/or sub-retinal fluid was 24% for brolucizumab 6 mg vs. 37% for aflibercept in HAWK (p=0.0001) and 24% vs. 39%, respectively, in the HARRIER study (P<0.0001). Absolute reductions in CST from baseline were -175 µm for brolucizumab 6 mg versus -149 µm for aflibercept in HAWK (p=0.0057) and -198 µm versus -155 µm, respectively, in the HARRIER study (P<0.0001).

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The Antibody Society maintains a comprehensive table of approved mAb therapeutics and those in regulatory review in the EU or US. Please log in to access the table, which is located in the Members Only section and can be downloaded in Excel format. Information about other antibody therapeutics that may enter regulatory review in 2019 can be found in ‘Antibodies to watch in 2019’.

Biologics license application submitted for eptinezumab, an anti-CGRP antibody for migraine prevention

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Alder BioPharmaceuticals has submitted a biologics license application (BLA) for eptinezumab, a humanized IgG1 monoclonal antibody that targets calcitonin gene-related peptide (CGRP), for migraine prevention. If the US Food and Drug Administration grants approval, Alder will be on track to launch the drug in Q1 2020. The BLA included data from the PROMISE 1 and PROMISE 2 studies, which evaluated the effects of eptinezumab in episodic migraine patients (n=888) or chronic migraine patients (n=1,072), respectively.  In PROMISE 1, the primary and key secondary endpoints were met, and the safety and tolerability were similar to placebo, while in PROMISE 2, the primary and all key secondary endpoints were met, and the safety and tolerability was consistent with earlier eptinezumab studies.

Alder announced one-year results from the PROMISE 1 study in June 2018, which indicated that, following the first quarterly infusion, episodic migraine patients treated with 300 mg eptinezumab experienced 4.3 fewer monthly migraine days (MMDs) from a baseline of 8 MMDs, compared to 3.2 fewer MMDs for placebo from baseline (p= 0.0001). At one year after the third and fourth quarterly infusions, patients treated with 300 mg eptinezumab experienced further gains in efficacy, with a reduction of 5.2 fewer MMDs compared to 4.0 fewer MMDs for placebo-treated patients.  In addition, ~31% of episodic migraine patients achieved, on average per month, 100% reduction of migraine days from baseline compared to ~ 21% for placebo. New 6-month results from the PROMISE 2 study were also released in June 2018.  These results indicated that, after the first quarterly infusion, chronic migraine patients dosed with 300 mg of eptinezumab experienced 8.2 fewer MMDs, from a baseline of 16 MMDs, compared to 5.6 fewer MMDs for placebo from baseline (p <.0001). A further reduction in MMDs was seen following a second infusion; 8.8 fewer MMDs for patients dosed with 300 mg compared to 6.2 fewer MMDs for those with placebo. In addition, ~ 21% of chronic migraine patients achieved, on average, 100% reduction of MMDs from baseline compared to 9% for placebo after two quarterly infusions of 300 mg of eptinezumab.

If approved, eptinezumab would become the fourth antibody therapeutic for migraine prevention on the US market, following the approval of erenumab-aooe (Aimovig; Novartis), galcanezumab-gnlm (Emgality; Eli Lilly & Company) and fremanezumab-vfrm (Ajovy; Teva Pharmaceuticals) in 2018.

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The Antibody Society maintains a comprehensive table of approved mAb therapeutics and those in regulatory review in the EU or US. Please log in to access the table, which is located in the Members Only section and can be downloaded in Excel format.