RARE Daily

FDA Approves Novartis Drug as First Targeted Therapy for SCD-Related Pain Crises

November 19, 2019

The U.S. Food and Drug Administration approved Novartis’ Adakveo to reduce the frequency of vaso-occlusive crises, a common and painful complication of sickle cell disease that occurs when blood circulation is obstructed by sickled red blood cells.

Sickle cell disease is a complex and debilitating genetic blood disorder that goes beyond sickle-shaped red blood cells. The disease is associated with chronic inflammation, which cause higher levels of cell adhesion proteins, including P-selectin, and make both the blood vessels and certain blood cells stickier and prone to multicellular interactions, or clusters, in the bloodstream. This environment can lead to the acute episodes of pain known as sickle cell pain crises, or VOCs, as well as life-threatening complications. VOCs are the main reason why individuals living with sickle cell disease seek medical care in hospitals, leading to approximately 200,000 emergency room visits in the United States every year.

Approximately 100,000 people in the United States have sickle cell disease. People of African ancestry make up 90 percent of the population with sickle cell disease in the United States. However, sickle cell disease is also prevalent among people of Hispanic, South Asian, Southern European, and Middle Eastern ancestry. Sickle cell disease occurs in about 1 in 365 African American births and 1 in 16,300 Hispanic-American births.

The FDA approved Adakveo to reduce the frequency of VOCs, or pain crises, in adults and pediatric patients aged 16 years and older with sickle cell disease. It is the first and only targeted biologic that works by binding to P-selectin, a cell adhesion protein that plays a central role in the multicellular interactions that can lead to vaso-occlusion in sickle cell disease. By binding to P-selectin on the surface of the activated endothelium and platelets, Adakveo blocks interactions between endothelial cells, platelets, red blood cells, and leukocytes.

The FDA’s decision to approve Adakveo is based on results of the 52-week, randomized, placebo-controlled SUSTAIN trial, which showed that Adakveo significantly lowered the median annual rate of VOCs to 1.63 vs 2.98 compared to placebo, which is equivalent to a 45 percent reduction. Reductions in the frequency of VOCs were observed among patients regardless of sickle cell disease genotype and/or hydroxyurea use.

The study also showed a median annual rate of hospitalized days to 4 from 6.87 days when compared to placebo. It also found 36 percent of patients treated with Adakveo did not experience a VOC compared to 17 percent of patients treated with a placebo.

The most common adverse reactions (incidence > 10 percent) were nausea (18 percent), arthralgia (18 percent), back pain (15 percent) and pyrexia (11 percent).

The FDA granted Novartis Priority Review and Breakthrough Therapy designation for Adakveo. Adakveo also received Orphan Drug designation.

“The approval of Adakveo marks a new era in the treatment of sickle cell disease, a genetic condition that places an extraordinary burden of unpredictable pain crises on patients and their families,” said Susanne Schaffert, president of Novartis Oncology. “The stories we have heard from patients about their sickle cell pain crises are devastating. We are pleased to help reimagine medicine together with the sickle cell community and offer new hope for fewer VOCs.”

Photo: Susanne Schaffert, president of Novartis Oncology

Author: Rare Daily Staff

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