AZD-8154

AstraZeneca CEO Pascal Soriot pictured above. (Rob Stothard/Getty Images) AstraZeneca reported its first-quarter financial reports. As is often the case, they updated their pipeline, and indicated they had dropped a few drugs, including a promising multiple myeloma drug. The first compound, MEDI2228, is an antibody-drug conjugate (ADC) targeting BCMA. BCMA (B-cell maturation antigen) is a transmembrane receptor found almost only on the surface of differentiated plasma cells. The company pushed MEDI2228 into Phase I trials in 2018, and in 2020, AstraZeneca reported a 61% objective response rate (ORR) at the maximum tolerated dose. There were no cases of keratopathy, a noninflammatory disease of the cornea, that had been observed in cases with a similar drug, GlaxoSmithKline’s Blenrep. There were other adverse effects. Blenrep was the first anti-BCMA drug to be approved by the U.S. Food and Drug Administration (FDA). In August 2020, the FDA approved Blenrep (belantamab mafodotin-blmf) as a monotherapy for adults with relapsed or refractory multiple myeloma who have received at least four previous therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor and an immunomodulatory agent. Multiple myeloma is the second most common blood cancer. It is generally treatable, but not curable. In the U.S. each year more than 32,000 people are diagnosed with multiple myeloma and about 13,000 die from it. There are a number of treatments for multiple myeloma, but many patients develop resistance to those drugs. This is partly why AstraZeneca apparently decided to drop development of MEDI2228 for this indication, because it not only faced competition from Blenrep, but from existing therapies. AstraZeneca and MedImmune, its global biologics research and development arm, also dropped MEDI6012, a lecithin-cholesterol acyltransferase (LCAT) for the treatment of atherosclerosis in patients with the most serious type of heart attack. This followed the wrap of a Phase II trial in adults with acute ST segment elevation myocardial infarction. In this case, it was abandoned for safety or efficacy reasons. Another project they dropped from the pipeline is its ATR kinase inhibitor ceralasertib in combination with Lynparza. It also ended a Phase I trial to evaluate ceralasertib and the BTK inhibitor Calquence, although it is continuing to study ceralasertib in other indications. AstraZeneca also removed AZD8154, an inhaled PI3Kgd inhibitor for asthma. After preclinical studies last year, they withdrew it and terminated the study, but the first-quarter report announced it had been officially pulled from the pipeline. Otherwise, the company reported revenue growth of 15% in the first quarter, of $7.32 billion. Not including the COVID-19 vaccine, revenue growth increased by 11% to $7.045 billion. “We delivered solid progress in the first quarter of 2021 and continued to advance our portfolio of life-changing medicines,” said Pascal Soriot, AstraZeneca’s chief executive officer. “Oncology grew 16% and New CVRM [Cardiovascular, Renal and Metabolism] grew 15%. New medicines contributed over half of revenue and all regions delivered encouraging growth. This performance ensured another quarter of strong revenue and earnings progression, continued profitability, and cash-flow generation, despite the pandemic’s ongoing negative impact on the diagnosis and treatment of many conditions. Given the performance in the first quarter, in line with our expectations, we reiterate our full-year guidance. We expect the impact of COVID to reduce and anticipate a performance acceleration in the second half of 2021.”