尋抗疫解方 美藥廠啟動巴瑞替尼臨床試驗 路透社 中文新聞 2020年4月11日（路透印第安納波利斯10日電）美國跨國藥廠禮來公司（Eli Lilly & Co）表示，將針對2019冠狀病毒疾病（COVID-19），展開藥物「巴瑞替尼」（baricitinib）療法的臨床試驗。禮來公司表示，已與美國國家過敏與傳染病研究院（NIAID）達成協議，將研究巴瑞替尼，審視這種藥物若用於治療2019冠狀病毒疾病住院患者，藥效和安全性如何。禮來公司先前曾試驗巴瑞替尼能否作為異位性皮膚炎的療法之一。禮來公司在聲明中表示，這項研究本月先在美國展開，之後擴及歐洲和亞洲其他地點，研究結果預計2個月內揭曉。中央社（翻譯）
Arguing the Case for Clinical Testing of Baricitinib for COVID-19 APR 10, 2020 | KENNETH BENDER, PHARMD, MA The likelihood that therapeutic agents against SARS-CoV-2 can be identified quicker by repurposing currently available products has impelled medical sleuths across the globe to sift through an array of medications for actions that could be directed at recently elucidated vulnerabilities of the virus. Justin Stebbing, MD, PhD, and colleagues at BenevolentAI, London UK described finding baricitinib, an agent approved for rheumatoid arthritis, by using artificial intelligence (AI) to search for candidates that might offer both antiviral and anti-inflammatory actions against SARS-CoV-2. The investigators sought agents in particular that inhibited AP2-associated protein kinase 1 (AAK1), a regulator of the endocytosis through which viruses can enter cells. "Disruption of AAK1 might, in turn, interrupt the passage of the virus into cells and also the intracellular assembly of virus particles," Stebbing and colleagues explained. Of 378 products that they found inhibited AAK1, 47 were approved for medical use and 6 of these inhibited AAK1 with high affinity. Among the candidates were oncology drugs that the investigators considered too dangerous to suggest for this application. Baricitinib, 1 of the 6 with high AAK1 binding, is a janus kinase (JAK) inhibitor that also binds the cyclin G-associated kinase, another regulator of endocytosis. This agent, the investigators noted, inhibits AAK1 within its approved therapeutic plasma concentrations. "We suggest it could be trialed, using an appropriate patient population with (COVID-19) acute respiratory disease, to reduce both the viral entry and the inflammation in patients," they indicated. The proposition drew a critical response from 1 group of rheumatologists, who were not only familiar with use of the agent for rheumatoid arthritis but also practiced in Lombardy, Italy, within the first European epicenter of coronavirus disease 2019 (COVID-19). Favalli and colleagues expressed concern about potential adverse effects, including interfering with the action of interferon, if it is employed to prevent viral replication. "The described mechanism affecting viral endocytosis mediated by 2 members of the numb-associated kinase family is one of the many unfamiliar effects of a relatively recent drug class, the real safety profile of which still remains to be definitively clarified," remarked Ennio Favalli, MD, Division of Clinical Rheumatology, ASST Gaetano Pini-CTO Institute, Milan, Italy, and colleagues. In response to their concern, Stebbing and colleagues pointed out that pegylated interferon is unlikely to be used for COVID-19. In addition, they clarified that they anticipate the timing of administering baricitinib would avoid early stages of the disease not requiring hospitalization, during which the virus is often cleared spontaneously. They suggest that with increased severity requiring hospitalization, "JAK-STAT pathway inhibition might be a potential strategy." In a subsequent correspondence in The Lancet Infectious Diseases, Stebbing and colleagues addressed a concern with the drug, identified in the US Food and Drug Administration stipulated black-box warning, about potential for serious infection, including with pulmonary pathogens. "The most significant side-effect seen over 4214 patient-years in the clinical trial programs used for European Medicines Agency registration was a small increase in upper respiratory tract infections," they indicated. They argued, further, that baricitinib would be a good agent to use in combination therapy with an antiviral such as remdesivir--currently nearing control trial results for COVID-19—as it has minimal interaction with the drug metabolizing cytochrome-P450 enzymes. Stebbing and colleagues close their case by claiming, "combinations of baricitinib with these direct-acting antivirals could reduce viral infectivity, viral replication, and the aberrant host inflammatory response."
Olumiant (baricitinib) granted Breakthrough Therapy designation by FDA Baricitinib has been granted Breakthrough Therapy as a treatment for alopecia areata, an autoimmune condition with no FDA-approved therapies. Man with alopecia areata - three bold spots on the side of his scalp/head. The developers of Olumiant (baricitinib) tablets, Eli Lilly and Company, have announced that the US Food and Drug Administration (FDA) has granted the drug Breakthrough Therapy designation for the treatment of alopecia areata (AA), an autoimmune condition that results in unpredictable hair loss. Breakthrough Therapy designation is designed to expedite the development and review of drugs intended to treat a serious condition when pre-clinical or clinical evidence suggests it may offer benefits over currently available therapies. "Patients with AA currently do not have any FDA-approved treatment options available to them," said Dr Lotus Mallbris, vice president of immunology development at Lilly. "AA not only causes hair loss but also may be a psychosocial burden for people living with this disease. At Lilly, we aspire to create new medicines that can give hope to patients. We look forward to working with the FDA to further explore baricitinib's potential to become the first approved treatment option for these individuals." The designation was based on the Phase II results of the adaptive Phase II/III study BRAVE-AA1. The adaptive study evaluated baricitinib against placebo in adult patients with AA. In the Phase II portion no adverse events were reported and the most common side effects were upper respiratory tract infections, nasopharyngitis and acne. The Phase II and Phase III trial results and an additional Phase II double-blind study (BRAVE-AA2), are currently being used to assess the efficacy and safety of the 2mg and 4mg doses of baricitinib relative to placebo. "There are millions of people around the world affected by and living with AA," said Dory Kranz, president and Chief Executive Officer of the National Alopecia Areata Foundation. "We're encouraged by baricitinib's potential to be one of the first FDA-approved medicines to treat AA." Baricitinib 2mg doses are currently approved for the treatment of adults with moderately to severely active rheumatoid arthritis (RA).
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