A Kura Oncology clinical trial that was paused in November after a patient death is now cleared to resume testing a drug for acute myeloid leukemia (AML) after the company reached an agreement with the FDA on measures to guard against a particular complication.
Kura announced the lift of the partial hold after the market close on Thursday. The San Diego-based biotech may now resume screening patients for the Phase 1b study, which is designed to find the appropriate dose to test in Phase 2.
The Kura drug, KO-539, is being evaluated as a treatment for cases of AML characterized a rearrangement of the KM2A gene. Kura’s small molecule blocks a protein called menin, which plays a role in the progression of leukemia in patients whose cancer carries that genetic signature.
The menin inhibitor drug class has a known complication risk called differentiation syndrome, in which cytokines, a signaling protein, are rapidly released from leukemia cells that are affected by the drug. Symptoms of the potentially life-threatening complication include fever, weight gain, breathing problems with blood or pus in the lungs, low blood pressure and kidney failure. Because this complication is known, clinicians watch for it. When the partial clinical hold was announced last November, Kura CEO Troy Wilson said that a “handful of cases” of differentiation syndrome were observed in all of the patients treated with KO-539, and those cases were managed with steroids.
Differentiation syndrome was raised as a potential cause of the reported patient death. However, Wilson said at the time that other factors could have contributed to the death. The patient had a complicated case that had failed to respond to four earlier lines of treatment. Also, fluid was observed around the heart, a problem that is not typically associated with differentiation syndrome. The cause of death could not be definitively determined as the patient’s family did not consent to an autopsy. Going forward, clinical trial investigators will keep close watch for signs of differentiation syndrome.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
“Our clinical protocol encourages investigators to monitor patients’ cell counts and intervene early with steroids and hydroxyurea if they see observe evidence or symptoms of differentiation syndrome,” Wilson said in an emailed statement. “If the symptoms of differentiation syndrome do not improve, we encourage investigators to use cytoreductive therapy and/or withdraw KO-539 until symptoms resolve. Our goal is to provide physicians with the tools to monitor and protect their patients and maximize the potential for anti-leukemic effect.”
In the announcement of the lift of the partial clinical hold, Wilson said that activities to resume patient screening are underway, and he expects the Phase 1b study will determine the recommended dose for Phase 2 testing in coming months. He added that KO-539 continues to be safe and well tolerated in patients, and is also showing clinical activity in patients currently enrolled in the study. Kura plans to provide a clinical trial update at a future medical meeting.
Photo by Flickr user ian munroe via a Creative Commons license
