10 antibody drugs that will receive regulatory approval in the US and Europe by 2020 (I)
The Antibody Society published a report at the end of November 2019, which analyzed the drug development advances in the field of antibodies. According to the report, in 2020, 12 antibody drugs will receive regulatory approval in the US or EU. However, the two drugs in the report, enfortumab vedotin and trastuzumab deruxtecan, have already been approved by the US FDA in advance in mid-to-late December 2019. Both are ADC drugs.
The following is a brief introduction to the remaining 10 antibody drugs in the report. Among them, the first 7 are for non-cancer indications, and the last 3 are for cancer indications.
Eptinezumab is a humanized IgG1 monoclonal antibody that targets the calcitonin-related gene peptide (CGRP) and was developed for the prevention of migraine. Migraine is a common chronic neurovascular disease, characterized by recurrent severe headaches. CGRP is a neuropeptide that has been shown to be released during migraine attacks, plays an important role in migraine pathophysiology, and is a popular target for migraine drug development.
Up to now, there have been 3 monoclonal antibody migraine preventive therapies targeting CGRP and its receptors: Amgen and Novartis Aimovig (targeting CGRP receptors) and Teva Ajovy (targeting CGRP) Lilly Emgality (targeting CGRP). Eptinezumab, developed by Alder BioPharmaceuticals, is administered by intravenous infusion once every 3 months. It has rapid and complete bioavailability, has high specificity and strong binding to CGRP inhibition, and has shown differentiated clinical characteristics in clinical research. In some patients it even showed a 100% response rate. Currently, the drug is under review by the US FDA. If approved, eptinezumab will be the first migraine preventive drug to be administered intravenously every quarter.
The drug is a fully human IgG1 monoclonal antibody that targets the insulin-like growth factor-1 receptor (IGF-1R) and was developed for the treatment of moderate to severe thyroid eye disease (TED). TED is a progressive, debilitating autoimmune disease caused by autoantigens activating IGF-1R-mediated signaling complexes on cells in the orbit, resulting in a series of negative effects, causing long-term, irreversible damage, including exophthalmos, strabismus, diplopia and even blindness.
The drug was developed by Horizon Pharma and the results of a confirmatory phase III OPTIC study published in March 2019 showed that, compared with the placebo group, patients with the teprotumumab treatment group had significantly improved eyeballs (primarily End point, p <0.001). Data from a phase II study showed that teprotumumab treatment resulted in clinically significant and statistically significant reductions in exophthalmos and active TED symptoms (pain, swelling, redness, inflammation).
Currently, the drug is undergoing priority review by the US FDA, and the PDUFA target date is March 8, 2020. Previously, the FDA has granted teprotumumab breakthrough medicine qualification, orphan medicine qualification, and fast-track qualification for active TED. Last month, the FDA's Dermatology and Ophthalmology Drug Advisory Committee (DODAC) unanimously approved and unanimously supported the potential benefits of teprotumumab for active TED outweigh the risks. If approved by the FDA, the drug will be the first to treat active TED.
Inebilizumab is a humanized monoclonal antibody that targets CD19 and was developed for optic neuromyelitis spectrum disorder (NMOSD), a rare, destructive, complement-mediated central nervous system (CNS) autoimmune disease, which is more common in women. The disease is characterized by relapses, and each relapse leads to the progressive accumulation of disability, including blindness and paralysis, and sometimes even premature death. About 80% of NMOSD patients have aquaporin-4 (AQP4) autoantibodies. These autoantibodies are thought to be produced by plasmablasts and plasma cells, which mainly bind to astrocytes in the CNS, trigger attacks, and damage optic nerve, spinal cord and brain.
Developed by Viela Bio, the drug has a high affinity for CD19, a protein widely expressed in B cells, including plasmablasts and some plasma cells that secrete antibodies. Inebilizumab is currently under review by the US FDA. In the United States and the European Union, the drug has been granted orphan drug status for NMOSD, and it has also been awarded breakthrough drug status for NMOSD in the United States.
Satralizumab is an anti-interleukin 6 receptor (IL-6R) humanized monoclonal antibody, which has been developed for the treatment of NMOSD. NMOSD patients experience severe, unpredictable relapses that directly lead to cumulative, permanent nerve damage. The drug can target IL-6R to inhibit IL-6 signaling. IL-6 is a cytokine and is believed to play a key role in the inflammation of NMOSD, triggering the inflammatory cascade, causing injury and disability.
Developed by Roche, Satralizumab is currently under review by the US FDA and accelerated evaluation by the European Union EMA. In the United States and the EU, the drug has been granted orphan drug status for NMOSD. Data from two global phase III clinical studies (SakuraStar, SAkuraSky) confirm the efficacy and safety of satralizumab as a monotherapy and in combination with a baseline immunosuppressant: (1) The SakuraStar study shows that across the entire study population and compared with placebo, satralizumab monotherapy significantly reduced the risk of recurrence by 55%, and reduced the risk of recurrence by 74% in patients with AQP4-IgG4 serology. (2) The SAkuraSky study showed that in the entire study population and compared with placebo + baseline immunosuppressive agents, satralizumab + immunosuppressive treatment reduced the risk of recurrence by 62%, and reduced the risk of recurrence by 79% in patients with AQP4-IgG4 serology.
In the United States and the European Union, Soliris is the only drug approved for NMOSD. It is given by intravenous infusion and is administered every 2 weeks during the maintenance period. Satralizumab is administered by subcutaneous injection once every four weeks, and if approved, it will be a more comprehensive treatment option for patients and caregivers.
Leronlimab is a humanized IgG4 monoclonal antibody that targets blocking chemokine receptor 5 (CCR5), a cellular receptor that plays multiple roles in HIV infection, tumor metastasis, and other immune-mediated diseases, including NASH. In the treatment of HIV infection, the drug belongs to a new class of therapies called viral entry inhibitors that can mask CCR5 and protect these cells from viral infection by blocking the entry of major HIV (R5) subtypes into healthy T cells. At the same time, leronlimab does not seem to interfere with the normal function of CCR5 in mediating the immune response.
Data from nine completed clinical studies have shown that leronlimab can significantly reduce or control patients' HIV viral load in each study. A phase IIb study showed that the drug's single-agent treatment could prevent HIV escape. Developed by CytoDyn, the drug has been successfully combined with standard antiretroviral therapy for critical phase III studies in HIV-infected patients, and is in the process of rolling forward to the United States FDA for a combined therapy biological product approval application (BLA). In addition to HIV, leronlimab is also being developed for a variety of cancers (including metastatic triple-negative breast cancer and immune diseases.
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