Novartis shoots for early OK of a ‘breakthrough’ blood cancer drug after reversing organ damage in trial

Up to now, Novartis’ midostaurin has been primarily noted for its potential in treating a mutation-specific type of acute myeloid leukemia, thrust into the spotlight after the FDA handed out its breakthrough designation for the drug earlier this year. But a new study shows that the drug also demonstrated a statistically significant ability to halt and reverse organ damage caused by rare cases of advanced systemic mastocytosis. And the pharma giant now plans to prep an application for regulators on both sides of the Atlantic in search of early marketing approval.

There are various kinds of mastocytosis, which is characterized by an over accumulation of mast cells in tissue. But advanced systemic mastocytosis threatens organ damage and death and one form – mast-cell leukemia – is invariably lethal.

Jason R. Gotlib, MD - Stanford University

Jason R. Gotlib, MD – Stanford University

“Midostaurin (PKC412) is a multikinase inhibitor, so it has several molecular targets,” Jason Gotlib, the lead investigator from Stanford, tells me. That makes it right for AML patients with a FLT-3 mutation. It also inhibits KIT D816V, a protein in the tyrosine kinase family which drives the development of mast cells.

To test it, investigators recruited 116 patients in an open-label study, without a control arm, including 89 with disease-related organ damage. 16 of the patients had the most aggressive form of the disease.

“Nothing works for them,” says Gotlib. But 8 of the 16 responded to the drug and “7 had complete resolution of organ damage” associated with longer survival.

The overall response rate Gotlib and his team tracked was 60%, with 45% of the patients achieving a “major response,” defined as  the complete resolution of at least one type of mastocytosis-related organ damage.

The median overall survival rate tracked in the study was 28.7 months, with the 16 mast-cell leukemia patients achieving a median OS rate of 9.4 months. But without a control arm, there’s no way to determine from this study if patients gained a survival advantage.

Even without a control arm in the study, though, Gotlib says the impact on organ damage and the absence of any effective therapies for the rare condition make it appropriate to seek out accelerated approval on the Phase II data. And a spokesperson for Novartis confirmed that the Big Pharma player is also readying its application for FLT-3 mutated AML.

“This is a drug that works,” Dr. Robert Hromas from the University of Florida told the UPI. “And until now, we’ve really had nothing.”

Hromas was not part of the study.

“Patients with advanced SM are part of a very small, highly underserved community that has suffered from a lack of medical innovation for many years,” said Alessandro Riva, the global head of Novartis Oncology Development and Medical Affairs. “Novartis…is now working with regulatory authorities to make midostaurin available as quickly as possible.”

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