The road to FDA approval for Cell Therapeutics, Inc. (NASDAQ: CTIC) has been one littered with speed bumps and potholes yet the biotechnology company now sits just a few months away from potentially clearing the final hurdle and advancing their primary drug pixantrone to commercialization. It goes without saying that the deck is still stacked against CTIC despite their ability to gain confirmation from a second independent radiology panel concerning the statistical significance of response and progression endpoints of their PIX301 pivotal trial for the treatment of non-Hodgkin’s lymphoma. As most investors recall an FDA advisory panel unanimously turned down pixantrone 9-0 back in 2009, citing numerous concerns about the efficacy and safety of the company’s trial.
Rather than conduct further clinical trials CTIC opted to appeal the FDA decision and while that decision was upheld the regulatory body left open a window of opportunity for the company. In their response to CTIC the FDA’s Office of New Drugs recommended the company conduct an additional review of radiographs utilizing a new independent panel of radiologists to confirm the response and progression events noted in the pixantrone NDA in order to determine that efficacy had been met.
CTIC went this route and actually earned confirmation from this second independent radiology panel which assessed the response and progression endpoint data of the PIZ301 trial and determined the statistical robustness of the efficacy data contained in the NDA. With that confirmation gained CTIC resubmitted their NDA and the FDA informed the company they would receive a six month review which could potentially earn them approval for pixantrone as early as April 2012.
Obviously this is what CTIC is banking on and company CEO James A. Bianco has remained optimistic about the outcome saying “We believe the resubmitted NDA not only addresses the items in the Complete Response Letter, but confirms the reliability of the initial efficacy results, which we believe demonstrates that pixantrone does provide a clinical benefit to this patient population for which there are no currently approved therapies.”
Whether the FDA shares the same opinion is not yet known but many shareholders have reserved their optimism having been disappointed before. Looking at the prospect of FDA approval for pixantrone it makes sense to be a bit cautious given the fact that the first go-around went horribly wrong. CTIC submitted their original NDA based on a trial that enrolled less than half the 320 patients it was designed to study. On top of the low enrollment only eight of the patients in the study were from the U.S. despite CTIC arranging for 28 U.S. sites to enroll patients. This is important to the FDA because patients in the U.S. tend to receive more pre-treatments which can affect their prognosis.
It was also discovered that 5 of the 14 patients who saw their tumors wiped out with the treatment of pixantrone actually had slow-growing tumors, not the fast-growing aggressive tumors that the patients in the study were supposed to have. Additionally there were six patients who quit taking pixantrone during the study because they had white blood cell depletion, an issue that wasn’t encountered in the control group. The study also produced severe heart toxicity in the enrolled patients, bringing up further questions about the safety of pixantrone. According to CTIC pixantrone “produced a favorable benefit to risk profile” for patients with no other options. While the FDA certainly recognizes the importance of approving treatments for patients that have no currently approved therapies they rarely base their decision on an argument that the patient doesn’t have any options so let’s just try this.
An important fact that should be remembered by investors is that pixantrone is targeted to treat relapsed or refractory aggressive non-Hodgkin’s lymphoma in patients who failed previous therapy. In fact the application for pixantrone is to use it as a third-line therapy, meaning two other therapies will have had to fail a patient before doctors turn to pixantrone. Essentially this makes pixantrone appear to be a Hail Mary; not only does the FDA have a hard time with this but even if approved it is something doctors could have a hard time recommending.
CTIC does have other drugs in their pipeline but the reality is they need to find success with pixantrone. The company is still awaiting news from European Union regulators, the European Medicines Agency, regarding their MAA for pixantrone and a decision is now expected to come sometime in early 2012. While the FDA will not base their decision on what the EMA does if CTIC can gain approval in Europe then it could prove influential.
At the moment it just seems difficult to believe the FDA will reverse their previous decision even with the confirmation from the second independent radiology panel. The concerns expressed by the FDA advisory panel back in 2009 still appear to exist and without a new trial to ease those concerns the prospect of FDA approval looks bleak.
Shares of CTIC have remained steady over the past few months, holding around the 1.09 – 1.15 range as shareholders still hold out hope. That share price range is about even with their 50-day moving average of 1.15 yet it still trails their 200-day moving average of 1.59. There will almost certainly be more activity picking up in the near future as CTIC gets closer to that April date with the FDA but with that activity there should be some volatility as investors place their bets.