Is PFS an approvable endpoint in sarcoma for Ziopharm? Bears say PICASSO 3 is being conducted without a special protocol assessment from FDA, and the ifo/dox data discussed above suggest that a PFS benefit isn't enough for FDA approval. Ziopharm, therefore, won't win FDA accelerated approval based on PFS or will be forced to delay an approval filing until it has survival data in hand.
In April, FDA approved GlaxoSmithKline's Votrient in sarcoma based on a statistically significant PFS benefit of three months over placebo. Granted, Votrient was approved in second-line sarcoma where Ziopharm is developing palifosfamide as a first-line treatment, but still, the idea that FDA won't approve a sarcoma drug without a survival benefit is just wrong. [Votrient did demonstrate a trend toward longer survival -- 12.6 months versus 10.7 months at the median -- but it wasn't statistically significant.]
In planning the PICASSO 3 trial, Ziopharm assumed doxorubicin PFS of 4.3 months, so the 4.6-month PFS observed in the dox arm of the ifo/dox study is re-assuring. Ziopharm's target is a 40% reduction (hazard ratio 0.60) in the risk of tumor progression for palifosfamide/doxorubicin over doxorubicin alone. I see that as quite achievable and approvable.
@Juliux asks, "$ONCY reported great data on phase 1 colorectal, phase 2 squamous cell lung, and phase 3 head/neck. Thoughts?" My first thought is, "Where are the great data?" In my view, Oncolytics Biotech has gone to great lengths to delay and obfuscate the Reolysin clinical trials. The data reported so far have been confusing for everyone and to me, clinically meaningless, to the point that the results appear to be designed only to divert attention from Reolysin's ineffectiveness. Let's focus first on the Reolysin "phase III" head and neck cancer trial, which isn't a true phase III trial any longer since Oncolytics can't use the data for FDA filing purposes. The original design was fairly straight forward. Oncolytics recruited 80 patients with platinum-refractory head and neck cancer (both loco-regional and metastatic disease) and randomized them to receive either 1) Reolysin plus carboplatin and paclitaxel or 2) placebo plus carboplatin and paclitaxel. The trial used an "adaptive" design, meaning an interim analysis of progression-free survival (PFS) was to be conducted on patients six weeks after enrollment. If the PFS data demonstrated a "meaningful benefit" (definition never truly defined) favoring Reolysin, the study would be expanded with additional patients enrolled and the primary endpoint switched to overall survival. Here's where the story gets squirrely, in my view. Enrollment in the Reolysin head-and-neck trial was slower than expected. The first PFS scan on the 80 patients took place late in the first quarter 2012, which should have allowed Oncolytics to announce results in April or May of last year. Instead, we got nothing from the company. The first-scan analysis (at six weeks post enrollment) was never released. (Was it done at all?) Instead, Oncolytics told investors that an interim analysis was being conducted after a second scan for PFS -- 12 weeks post enrollment for all patients. This analysis was expected in July or August of last year.
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