About two months ahead of the priority review action date, Novartis AG scored FDA clearance for Adakveo (crizanlizumab), previously known as SEG-101, to reduce the frequency of vaso-occlusive crises (VOCs), or pain crises, in adult and pediatric patients ages 16 and older with sickle cell disease (SCD).

It's the first FDA-approved drug in SCD that binds to P-selectin, a cell adhesion protein that plays a key role in multicellular interactions that can lead to VOCs. Basel, Switzerland-based Novartis said Adakveo will be available in "the coming weeks."

The FDA's go-ahead for Adakveo at the 5-mg/kg dose is based on results of the 52-week, randomized, placebo-controlled Sustain trial, which showed that the drug significantly lowered the median annual rate of VOCs to 1.63 vs. 2.98 compared to placebo (p=.010), which is equivalent to a 45% reduction. Reductions in the frequency of VOCs were achieved regardless of sickle cell disease genotype and/or hydroxyurea use, the company noted.

Some 100,000 people in the U.S., most of whom are of African descent, have SCD, a genetic blood disorder characterized by sickle-shaped red blood cells. The disease is associated with chronic inflammation, causing higher levels of cell adhesion proteins, including P-selectin, which makes blood vessels and certain blood cells stickier and prone to multicellular interactions, or clusters.

SCD therapies remain the focus of research. This summer, Rockville, Md.-based Glycomimetics Inc. reported the failure of the phase III Reset trial with rivipansel, which missed the primary endpoint as well as key secondary efficacy endpoints. Pfizer Inc., of New York, and Glycomimetics agreed in 2011 to develop and commercialize the pan-selectin agonist. (See BioWorld, Aug. 6, 2019.)

Up and coming is Cambridge, Mass.-based Fulcrum Therapeutics Inc.'s FTX-6058, for which an IND is expected in the middle of next year. It's a small molecule that acts to induce human fetal hemoglobin (HbF) levels, a clinically validated approach to address the root cause of SCD. In preclinical in vitro and in vivo data, FTX-6058 showed it could dose-dependently increase HbF cells to about 20%. H.C. Wainwright analyst Andrew Fein likes the prospect, saying in an Oct. 3 report that FTX-6058 "compared to [Novartis' just-approved therapy], is relatively inexpensive to manufacture, and involves less complicated logistics."

A laboratory team at City of Hope in Los Angeles recently published in Scientific Reports findings with a modified version of CRISPR/Cas9 editing. The method worked better at normalizing HBB and BCL11A, genes known to be implicated in SCD, by nixing a portion of their DNA sequence that normally ends the production of fetal hemoglobin. Modifying somewhat the sgRNA used by Cas9 to recognize the DNA sequence of the targeted gene, that method might prove useful in HIV as well.

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