By Basem M. William, MD

On Monday, the Director of the Division of Hematology Products in the Office of Hematology and Oncology Products at the U.S. Food and Drug Administration (FDA), Ann Farrell, MD, chaired the two special ASH-FDA Joint Symposia focusing on new drugs for nonmalignant and malignant hematologic diseases. “The goal of the ASH-FDA Joint Symposium on New Drug Approvals is to inform hematologists about emerging scientific effectiveness and safety issues, to cover the breadth of the agency’s approvals for the treatment of a variety of malignant and nonmalignant conditions, and to highlight the basis for these approvals,” Dr. Farrell explained.

L-glutamine was the first disease-modifying agent for sickle cell disease (SCD) to be approved by the FDA in 20 years — a landmark event in the history of the disease. 2019 marks yet another landmark with the FDA approval of two new SCD drugs: voxelotor, an oral agent preventing hemoglobin polymerization, and crizanlizumab, a monoclonal antibody blocking P-selectin. The latter drug is aimed at decreasing the frequency of vaso-occlusive crises — the most devastating manifestation of SCD that leads to severe pain and subsequent end-organ damage. Voxelotor is designed to address the underlying anemia and hemolysis associated with SCD by directly inhibiting hemoglobin polymerization, through the increase of hemoglobin levels.

Acute hepatic porphyria (AHP) is an enigmatic disease presenting with vague recurrent abdominal pain and neuropsychiatric symptoms, positioning itself into that zone between critical illness, neurosis, and royal tales, captivating the curiosity and challenging the skills of internists for a very long time. The FDA also approved givosiran as the very first disease-modifying agent ever developed for the treatment of AHP. Givosiran is a double-stranded small interfering RNA that causes degradation of aminolevulinate synthase 1 (ALAS1) mRNA in hepatocytes through RNA interference, and reduces the elevated levels of liver ALAS1 mRNA. This is also an exciting year for the treatment of hematologic malignancies, marked by the FDA approval of multiple new agents. Acalabrutinib, a highly selective Bruton tyrosine kinase inhibitor developed to minimize off-target activity of ibrutinib, and currently approved for relapsed/refractory mantle cell lymphoma, has been approved for relapsed/refractory chronic lymphocytic leukemia (CLL). Polatuzumab, a CD79b-directed antibody-drug conjugate, was approved for relapsed/refractory diffuse large B-cell lymphoma in combination with bendamustine and rituximab. Ruxolitinib, a combined JAK1/JAK2 inhibitor previously approved in myelofibrosis, received approval for acute graft-versus-host disease in adult and pediatric patients. This session will also cover the circumstances behind the FDA-issued safety warning on the use of venetoclax and check-point inhibitors in patients with multiple myeloma.

This Special-Interest Session provided a great opportunity to become informed about these and other important new drugs, as well as expanded indications for existing drugs. Beyond learning about specific agents, the presentation provided a great opportunity to gain more insight into the “Step by Step” process that informs FDA evaluation and approval of new drugs.

Dr. William indicated no relevant conflicts of interest.

Editor’s Note: This article amends an incorrect statement about voxelotor that appeared in print and should be considered the version of record.


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