Eli Lilly’s rheumatoid arthritis medication, Olumiant (baricitinib), is currently in phase 3 clinical trials to become a potential drug used in the treatment of COVID-19.
This discovery was made possible by artificial intelligence analysis by BenevolentAI. BenevolentAI used machine learning to read through scientific literature to search for an approved drug that has the capability of blocking 2019-nCoV from entering lung cells and stopping the viral infection process. 2019-nCoV is thought to enter cells through receptor-mediated endocytosis, specifically using ACE2 receptor found on the lung AT2 alveolar epithelial cells. The AI analysis specifically looked at approved drugs that are inhibitors of AAK1, or AP2-associated protein kinase 1, a known regulator of endocytosis. Out of the 378 AAK1 inhibitors, 6 of them showed high affinity for this target. 2 of these drugs, sunitinib and erlotinib, are cancer medications and unfortunately showed too many side effects at the doses needed to be effective. Baricitinib (Olumiant from Eli Lilly), on the other hand, showed inhibition of AAK1 at therapeutic doses, and thus has been selected to be trialed. The figure below shows the BenevolentAI knowledge graph showing the relationships between the suggested drugs and their targets in the body.
Figure 1 BenevolentAI knowledge graph
The phase 3 trial for Olumiant began June 15th and currently enrolled 400 hospitalized patients. It is testing whether Olumiant can cut the rate of death or need for ventilation or other oxygen support. It will compare the proportion of deaths or ventilation by day 28 between Olumiant and placebo. Other areas of study will include clinical improvement, length of hospitalization, and time to recovery. It is known to control inflammation in arthritis patients through inhibition of JAK1 and JAK2, and it is hoped that this will also be helpful in COVID-19 since a major problem with the infection is the occurrence of a cytokine storm, an overreaction of the inflammatory process in the body. Thus, this drug may have the capability of reducing viral infectivity through inhibition of AAK1 as well as reducing inflammation through JAK1 and JAK2.
This trial will complement data from the study of baricitinib with remdesivir in the Adaptive COVID-19 Treatment Trial (ACTT-2). President of Lilly Bio-Medicines, Patrik Jonsson, says that this will not be the final step in defeating COVID-19, but rather it is “a very important first step” and that antibody therapy or a vaccine will be that final step. Lilly has begun two antibody trials in addition to Olumiant in recent weeks.
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By: Stephanie Scuotto, PharmD Candidate 2022