NCHR Testimony at FDA at the Onolcogy Drugs Advisory Committee Meeting on Quizartinib

Varuna Srinivasan, MBBS, MPH, National Center for Heath Research; May 14, 2019

Thank you for the opportunity to speak today. My name is Dr. Varuna Srinivasan. I am a physician with a Master’s in Public Health from Johns Hopkins University. I am speaking today as a Senior Fellow at the National Center for Health Research, which analyzes scientific and medical data to provide objective health information to patients, health professionals, and policymakers. We do not accept funding from drug and medical device companies, so I have no conflicts of interest.

We have several serious concerns about Quizartinib:

Let me start by saying that we understand that AML with positive FLD3-ITD is a deadly disease.  More than three out of four of the patients died while participating in the Study AC220-007, and that did not differ significantly when comparing Quizartinib to chemo.  However, we are concerned that Quizartinib was compared to chemotherapy that was known to not be effective, rather than to one of the newer treatments of the same drug class.  For example, Gilteritinib has a 21% complete remission rate, compared to 4% for Quizartinib and only 1% in the chemo group.  The median overall survival was 9.6 months compared to 6.2 months for patients on quizartinib.

Patients on Quizartinib were twice as likely to die within 30 days of their last dose (33% vs. 17%).  Quizartinib patients were also more than twice as likely to die from lack of efficacy (25% compared to 10%.) Those are substantial differences that raise important questions about the drug.

On the other hand, Quizartinib patients were less likely to die by day 30 of the study or by day 60 of the study. They were also lived slightly longer after diagnosis.  These are relatively small studies and while the difference in overall survival was significant, event-free survival was not.  Since there was no difference in the cause of death, those findings are confusing.

The sponsor says:  ‘Treatment should be continued as long as the patient continues to benefit from the therapy or until unacceptable toxicity occurs’. That seems rather vague instructions for a cancer drug, especially one with a high risk of cardiac toxicity.

Unfortunately, the sponsor provided no information about the quality of life of patients on Quizartinib compared to chemo.   Quality of life is very important since neither of these treatments has a high success rate for overall survival and both have very low success rates in terms of complete remission (4%).

FDA reported that 1-2% of Quizartinib patients died from cardiac-related causes. The novel method of action of this drug on the chloride channels of the heart makes it fairly dangerous for some patients potentially leading to arrhythmias and cardiac arrest.  However, this did not seem to be a higher rate of death from adverse events than chemo.

Patients with this disease do not live very long on average after diagnosis. Current treatment with chemotherapy often leaves patients with low quality of life with an extension of only a few weeks as part of their overall survival. We need new treatments for this deadly disease, but we need to know if a new drug is BETTER than existing treatments.  The fact that Quizartinib is quite similar in risks and benefits to chemo, which is not very effective and provides a poor quality of life, is not a good reason to approve this drug.

At the least, the sponsor should determine which patients are most likely to benefit, and also evaluate the quality of life.

We urge the panel today to consider these points while discussing and voting today.