Read on Twitter
Intravesical nadofaragene for BCG-refractory NMIBC.
A single-arm trial.
I have a couple of questions.
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30540-4/fulltext
1/
A single-arm trial.
I have a couple of questions.
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30540-4/fulltext
1/
Historical context for this trial is important. In 2014, @US_FDA convened a meeting of clinical experts to advise on trial design for non-muscle-invasive bladder cancer, an area of unmet clinical need.
https://pubmed.ncbi.nlm.nih.gov/24332121/
2/
https://pubmed.ncbi.nlm.nih.gov/24332121/
2/
The panel discussed, but made no recommendation, whether trials randomizing to new therapies vs. physician choice of existing therapies should be done. The panel DID feel that single-arm trials were appropriate, and specified the critieria for clinically meaningful benefit:
3/
3/
So, the minimal clinically meaningful benefit was felt to be 30% ongoing response at 18-24mo, with confidence intervals excluding 20%.
What did nadofaragene firadenovec, the new gene therapy, achieve?
4/
What did nadofaragene firadenovec, the new gene therapy, achieve?
4/
The carcinoma in situ population (the group corresponding to the panel recommendation above), is in the first column.
At 12mo (ie, with more time for recurrences before getting to 18-24mo), there were 24.3% of patients still responding. With a lower 95%CI of 16.4%.
5/
At 12mo (ie, with more time for recurrences before getting to 18-24mo), there were 24.3% of patients still responding. With a lower 95%CI of 16.4%.
5/
So, two questions.
First, for everyone:
Am I reading these numbers right? The 12mo HGR-free stat w/in CIS population seems to me the most appropriate to compare nadofaragene firadenovec to the FDA panel recs. But are these numbers incomparable, for reasons I haven't realized?
6/
First, for everyone:
Am I reading these numbers right? The 12mo HGR-free stat w/in CIS population seems to me the most appropriate to compare nadofaragene firadenovec to the FDA panel recs. But are these numbers incomparable, for reasons I haven't realized?
6/
Second question, if I'm not reading this wrong, is for the FDA:
Is the FDA going to approve a therapy that did not meet the specified threshold for clinically meaningful benefit identified by the public workshop panel it convened?
7/
Is the FDA going to approve a therapy that did not meet the specified threshold for clinically meaningful benefit identified by the public workshop panel it convened?
7/
