Replies to post #85190 on Biotech Values

[DewDiligence]

…not sure which dose PFE is carrying forward

The CP-690,550 doses in all phase-3 RA trials are 5mg and 10mg.

Methotraxate ± CP-690,550 in second-line* setting:
http://clinicaltrials.gov/ct2/show/NCT00847613

CP-690,550 monotherapy vs placebo in second-line setting:
http://clinicaltrials.gov/ct2/show/NCT00814307

(CP-690,550 + methotrexate) vs (Humira + methotrexate) in second-line setting:
http://clinicaltrials.gov/ct2/show/NCT00853385

“Clinician’s choice” DMARD ± CP-690,550 in third-line setting:
http://clinicaltrials.gov/ct2/show/NCT00960440

5-year open-label extension trial (for previously enrolled patients):
http://clinicaltrials.gov/ct2/show/NCT00413699

*Whether this trial is first-line or second-line is a matter of semantics. Patients must be on methotrexate monotherapy at the time of enrollment, but they need not have progressed while on it.

[DewDiligence]

Re: CP-690,550 mono vs combo data

…it's interesting that the ACR scores are higher across the board for the monotherapy treatment arm compared to the combination-therapy arm, which incorporated methotrexate.

The “placebo” arm in the combination study was methotrexate monotherapy.
Thus, although the magnitude of the ACR discrepancies between the mono study and the combo study is surprising, it’s not surprising, IMO, that the placebo-adjusted ACR scores were higher in the monotherapy study than in the combination study.

When one combines drugs that do not have a synergistic MoA, the Law of Diminishing Returns comes into play and the result is often less than additive efficacy.

p.s. The placebo-adjusted DAS28 Remission number for the 5mg dose was better in the combination study than in the monotherapy study, but this outcome was just statistical noise, IMO. Moreover, DAS28 Remission is a controversial metric that some clinicians think has little relevance in the real world.