As rivals march on, Novartis secures priority FDA review for sickle cell disease therapy
About a month after rival Global Blood Therapeutics $GBT unveiled positive pivotal data on its sickle cell disease drug, Novartis’ $NVS therapy for the blood disorder has been granted a speedy review by the FDA.
Touted by Novartis chief Vas Narasimhan as a potential blockbuster, the Swiss drugmaker’s drug, crizanlizumab, in January secured the FDA’s breakthrough therapy designation for its ability to prevent debilitatingly painful vaso-occlusive crisis (VOCs) for patients affected by the group of inherited red blood cell disorders that typically afflict those of African ancestry.
Sickle cell disease patients have atypical hemoglobin molecules, which can distort red blood cells into a sickle, or crescent, shape. Symptoms such as anemia, repeated infections and periodic episodes of pain called vaso-occlusive crises (VOC) when sickle-shaped red blood cells get stuck inside blood vessels begin to appear in early childhood. These episodes deprive the body of oxygen-rich blood, which can culminate in widespread tissue and organ damage — particularly in the lungs, kidneys, spleen, heart and brain — and drastically diminish life expectancy.
For now, bone marrow transplants offer the only potential cure for sickle cell anemia — but the procedure is not safe enough for patients older than 16 — besides securing a healthy donor is difficult and the risks can be life-threatening. Therefore, treatment is typically limited to avoiding crises, relieving symptoms and preventing complications. Hydroxyurea, a drug believed to stimulate the production of fetal hemoglobin, is often given daily to reduce the frequency of painful crises — but it increases the risk of infection, and the risks associated with long-term use are unclear.
Novartis’ monoclonal antibody, called crizanlizumab or SEG101, is administered intravenously and engineered to bind to a molecule called P-selectin, one of the major drivers of the vaso-occlusive process. Novartis gained access to the drug in 2016 via an acquisition of Selexys Pharmaceuticals in a deal valued at up to $665 million.
The drug has shown to reduce the median annual rate of VOCs leading to health care visits, and an analysis of Phase II data presented at the ASH conference last year also showed that 35.8% of those given the experimental treatment did not experience a VOC, versus 16.9% on the placebo arm in patients with a history of 2-10 VOCs in the preceding year. After initially suggesting a marketing application would be submitted in 2018, Novartis said it would make its case for the drug in 2019.
Last month, Global Blood Therapeutics said it was poised to submit an application for accelerated approval for its once-daily pill voxelotor — which is designed to work by increasing hemoglobin’s affinity for oxygen — in the second half of this year. Data presented showed the drug conferred a sustained improvement in oxygen-rich hemoglobin levels, and was also associated with fewer VOCs — a key secondary endpoint — but the difference wasn’t statistically significant.
“While Novartis portrays an advantage of potentially having crizanlizumab approved ahead of voxelotor, we believe voxelotor has an edge on convenience. Ultimately, we don’t view the drugs as direct competitors, but rather complementary treatments, given both drugs show beneficial results in different measures, and work through different mechanism of actions,” Cantor Fitzgerald analyst Elemer Piros wrote in a note.
In 2017, Emmaus Life Sciences secured SCD approval from the FDA for Endari — a pharmaceutical version of L-glutamine, a drug sold over-the-counter as a nutritional supplement. EU regulators in contrast recently recommended the drug not be approved on the basis that the data from the main trial did not show it was effective at reducing the number of sickle cell crises or hospital visits, and a high drop-out rate in the study.
GBT last August licensed a P-selectin antagonist, inclacumab, from Roche. Other drugmakers, including bluebird Bio $BLUE, Imara, and partners CRISPR Therapeutics and Vertex $VRTX, are also working on their own therapies. Pfizer $PFE and GlycoMimetics $GLYC are testing their SCD drug, rivipansel, in an ongoing Phase III study.
In a note published in late June with commentary from a key opinion leader, Cowen analysts laid out the potential landscape of SCD therapies.
“BLUE’s LentiGlobin showed impressive data and has a potential to be curative…GBT’s Voxelotor needs more meaningful data to prove real-world efficacy and safety. NVS’s crizan has compelling data likely to garner approval in 18+ yo and PFE/GLYC’s Rivipansel Ph3 study design has some elements that raise concerns, but might still be approvable.”
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