| |
FDA Perspectives on Clinical Trial Design for New HCV Products, Early Access, presented by Kim Struble at EATG meeting Nov 21 2009, Brussels
|
| |
| |
Reported by Jules Levin
I attended this meeting completed saturday in Brussels, attended by European community advocates, EMEA, FDA, and drug companies.
Several noteworthy points made by Kim Struble, FDA:
-- monotherapy studies are to be no more than 3 days to minimize potential development of drug resistance and should collect intensive PK, safety, HCV RNA decay & resistance data
-- in the 8th slide titled "Dose Finding" it says that to bridge from a proof-of-concept phase to phase 2 dose finding trials in treatment-naives the developer can "use week 12 on-treatment data to design phase 2 dose finding in larger population", and "based on Week 12 data simultaneous phase 2 trials in naive and experienced possible". This appears to provide advice by the FDA, I think new advice, and companies can accelerate the clinical trials process. So, companies can go right from week 12 data in naives into coinfection studies as long as they have PK and drug-drug interactions, this can accelerate coinfection studies.
Kim Struble says "patient populations to benefit from use of 2 or more oral antiviral agents:
--SOC null responders
--patients for whom SOC contraindicated such as decompensated liver disease or severe anemia
--patient not able to tolerate SOC
--transplant patients and patients with decompensated cirrhosis
--genotype 1 a/b treatment-naive or experienced
to improve on SVR rates when added to SOC: African-Americans, HCV/HIV coinfected"
In other words this appears to suggest these special patient populations can greatly benefit from 2 oral drugs plus SOC and I think says companies should pay special attention to developing regimens containing 2 orals for coinfected, null responders, transplant patients (pre & post transplant), African-Americans and patients who cannot tolerate SOC. The FDA should give incentive to companies paying special attention to these patient populations by accelerating development & clinical trials for these patient populations.
Kim Struble says prerequisite data are needed to study special populations and are encouraged to be collected early in development: transplant, decompensated cirrhosis, coinfection - some data in compensated HCV infected patients, PK in hepatic impairment and drug-drug interactions. This means in order to accelerate clinical trials studies in these patient populations PK and drug-drug interaction studies as well as studies in hepatically impaired patients need to be conducted early & prioritized in order to accelerate the starting of clinical trials in these special patient populations.
FDA "strongly encourages initial NDA contain some clinical data on coinfected patients at time of filing: drug-drug interactions, safety data on a cohort of coinfected patients receiving the drug for the recommended treatment duration; preliminary efficacy data characterizing, at minimum, on-treatment responsees; labeling describing drug interactions and preliminary safety data would be appropriate; to expand indication to HIV coinfected:
--trial in at least 30 coinfected, single arm may be acceptable if HCV monoinfected population shows robust and substantial efficacy of new DAA, endpoint of SVR at week 24 after end-of-treatment; safety evaluation includes loss of HIV efficacy!
EARLY ACCESS/Treatment IND
--depends on willingness of pharmacurical sponsor
--FDA supports concept when sufficient data available to characterize reasonably safe and active dose
TIMING:
--after phase 3 trials are fully enrolled or well underway as to not interfere with development
--alternatives (these can occur earlier in drug development):
- individual patient INDs
- treatment access protocols for intermediate size populations (about 100 patients or less)
Can include multiple investigational agents or allow for co-enrollment into severa; IND programs simultaneously
SO, this says, as I have been emphasizing, that a path to early access can be "treatment access protocols" or in other words the companies can conduct studies, one-arm open-label studies, to provide access to patients with special needs including coinfected, if safety, drug-drug interactions, PK and data from hepatic impairment have been already collected. This is why I call the concept Early Access rather than Expanded Access, we need a different & new approach to HCV compared to HIV.
|
|
| |
| |
|
|
|
