Biotech Values

[dewophile]

CLVS

It is in the 10K

https://d18rn0p25nwr6d.cloudfront.net/CIK-0001466301/3a07cd1a-176c-415e-a81b-6ae176983131.pdf

We are currently evaluating the timing of our planned sNDA and Type II variation submissions. As suggested by the
recent Oncologic Drugs Advisory Committee (“ODAC”) involving PI3K inhibitors, and our recent discussions with the FDA
on May 3 and 4, 2022, the FDA is placing increasing emphasis on overall survival (“OS”) in oncology trials. Despite the fact
that the ATHENA-MONO trial met its primary endpoint, and OS is a secondary endpoint, the FDA advised us that we should
not submit the first line maintenance sNDA until OS data from the ATHENA-MONO trial are as much as 50% mature, and if
we do choose to submit prior to that, we should expect the FDA to require a discussion at an ODAC meeting in connection
with its review of such sNDA submission. This recommendation by the FDA was also influenced by their interpretation of the
ARIEL4 survival data. Currently, the OS data are approximately 25% mature and our initial estimates suggest we would reach
50% maturity in approximately 2 years. We have not yet initiated discussions with EMA.
At the current maturity, the hazard ratios of the OS in ATHENA-MONO in the HRD-positive and ITT populations are
0.96 and 0.97, respectively. As reported in the New England Journal of Medicine, the OS in the PRIMA first line maintenance
trial of niraparib was only 11% mature at the time it reported its primary endpoint. Hazard ratios in the HRD and ITT
populations of PRIMA were 0.61 and 0.71, respectively. At the time the primary results of the PAOLA-1 first line
maintenance trial of olaparib+bevacizumab primary endpoint were reported, OS was 26% mature and the HR in the ITT
population was 1.01 as described in the European Public Assessment Report. As reported in the New England Journal of
Medicine, at the time the SOLO-1 first line maintenance trial of olaparib primary endpoint was reported, OS was 21% mature
and the HR in the ITT population was 0.95.
In light of this unexpected recommendation from the FDA, we are developing our strategy for next steps and potential
timing of our sNDA submission in consultation with clinical advisors and outside counsel.