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Over the next couple of weeks, I’ll be posting stories gat...
Today I gave the following talk to AAADV. I'm heartened by the notable interest in pediatric expansion cohorts.
REASONS TO PUSH FORWARD WITH PEDIATRIC EXPANSION COHORTS REMARKS TO AAADV MAY 5, 2016 NANCY GOODMAN
Change is hard. Change is messy. But, as with any new step forward, creating pediatric expansion cohorts would make seriously ill children that much healthier.
I would like to extend a special thank the FDA and Greg Reaman for convening this panel and leading the effort on this critical step. The FDA are truly the champions of children with pediatric cancer.
1. Reasons why we should try: because other wise kids suffer
My son, Jacob, died of medulloblastoma when he was 10 years old. The treatment he received had not materially changed in 40 years.
Soon after completion of Jacob’s upfront therapy, Jacob’s oncologist at NYU, Sharon Gardner, told my husband and me that Jacob’s prognosis was dire and that the available treatments were unlikely to be curative.
We understood that the only way to protect Jacob was for him to try novel, unapproved therapies. We understood the risk involved in being treated with unapproved therapies. We were not concerned about painful toxicities – Jacob had already endured 9 weeks of unmanaged pain from hydrocephalus, cognitive deficits, posterior fossa syndrome with profound neurological impairments, and the collapse of his GI system.
We were concerned about earlier death, but we were willing to risk this if the data for an extended life was good enough. The bar was low.
There were no open pediatric brain cancer trials with unapproved agents.
Jacob had upfront therapy of surgery, radiation and chemotherapy, a metronomic therapy, two rounds of experimental high dose therapy, and six weeks of ad hock palliative chemotherapy. These protocols, specifically the high dose, were as toxic as anything that Jacob would have been treated with had he been granted access to an unapproved therapy.
One reason to begin using pediatric expansion cohorts is that this strategy could help children like Jacob.
The other reason to try to adopt pediatric expansion cohorts is that the alternative is not always careful, later studies. It is to a large extent the treatment of children with off label drugs in a setting in which toxicity and efficacy data is not collected an a recommended dose is unknown. Post market pediatric studies are slow to accrue and control arms do not offer equipoise.
2. Reasons why it’s doable: industry says they can do it
I will skip the regulatory conversations my co-panelists will make, with the exception of 2 points.
First, kids can be taught to swallow pills as they do in HIV + trials and many pills are scored.
Second, I’m not sure how often juvenile toxicity studies are really necessary when adult data is available and even when the FDA does not want it! This is really an EMA issue.
3. Political opportunities: KIDS INNOVATIVE DRUGS ACT
I would like to end by bringing to your attention a bill we are championing that would make pediatric expansion cohorts a more compelling business decision for companies.
This is, the KIDS INNOVATIVE DRUGS ACT (KIDS ACT) to reform Pediatric Research Equity Act, (commonly referred to as PREA).
Under PREA, a company developing a drug for a certain indication is required to undertake pediatric studies if there are pediatric populations who have that indication. However, PREA has not in the past applied to cancer drug development because children have different types of cancer. Children do not get breast or prostate cancer.
Under the KIDS Act, pediatric studies would now be required if the molecular target for which the drug is being developed is present in a pediatric cancer even if it is a pediatric cancer of a different histology than the adult cancer.
The KIDS Act has a good chance of being passed into last in 2016 or 2017. At that time, the FDA would have the opportunity to request pediatric expansion cohorts as part of a PREA study requirement.
We hope Congress will accept the KIDS Act as part of CURES. If not, we will ask Congress to pass it as part of PDUFA. ... See MoreSee Less