I’m Dr. Diana Zuckerman, president of the National Center for Health Research. We scrutinize the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products. Our largest program is focused on cancer. My expertise is based on post-doc training in epidemiology and public health, and my previous positions at HHS and as a faculty member and researcher at Harvard and Yale.
In April this same Committee examined 6 randomized trials of Pi3K inhibitors used for hematologic malignancies and found that all reduced overall survival –despite potential benefit for PFS. FDA says that these consistent findings across multiple randomized trials within the same drug class is unprecedented in oncology.
That’s a shocking finding that we need to take seriously. And that’s the context for today’s meeting.
The sponsor did a 5-year randomized controlled post-market study – 3 years longer than the data that resulted in initial approval. They found the median OS was 11 months shorter than the comparison drug. In fact, 50% of the patients died during those 5 years, compared to 44% taking the other treatment – a treatment that is no longer considered effective and so is rarely used.
Then they analyzed patients with 2 or more prior therapies, since that was the indication. Those Copiktra patients lived about 3 months shorter – not as bad as the larger sample, but still worrisome. Especially since 56% died during the 5 years of the study, compared to 49% assigned to the other treatment.
Adverse events caused the deaths of 15% of the Copiktra patients compared to only 3% of the other treatment group. And the percentage of Grade 3 or greater AEs was 91%, and 78% had Serious AEs–about twice as high as the comparison group. This has clear implications for quality of life, in addition to the patients not living as long.
The FDA did the right thing by requesting this post-market study. And the sponsor did the right thing by completing the study. Now is the time to listen to the results. We urge this Advisory Committee and the FDA to make it clear that approvals will be rescinded when evidence indicates that promising short-term results are reversed based on longer term data from post-market studies.
Patients and oncologists want as many treatment options as possible, but we do patients no favors by maintaining approval for a drug that does more harm than good. As was true yesterday for other cancer treatments, the preponderance of evidence is clear today.
As a cancer survivor myself, I understand the need for treatment options. I thank this committee and the FDA for its objective, scientific analysis of the data presented yesterday and today. I hope it will help everyone understand that an individual patient may seem to do well on a specific treatment, but that treatment may not be the REASON the patient did well. There are other individual differences that cause some patients to do better than others, and to live longer than others. As FDA stated, these diseases are often indolent. That’s why large, long-term randomized controlled trials are so important – to help us understand which treatments are better for which patients.
There are so many problems with the data, including the very substantial changes in treatment standards that have occurred since this study was designed, the low number of US patients, and the dearth of nonwhite patients – all these support rescinding approval for this indication.
It takes years for FDA to rescind approval unless the sponsor does the right thing by voluntarily doing so. But your vote today will be very influential.
I hope that the sponsor will conduct new research to determine if a subgroup of patients can benefit from this drug under current treatment standards, and if a lower dose is safer as well as effective, and if so FDA should of course consider approval for a different indication. But that isn’t where we are today.