The bad news keeps coming for Poniard Pharmaceuticals’ platinum-based chemotherapy treatment picoplatin. What the company happily tried to portray on Sunday as a successful phase II trial in metastatic colorectal cancer - in that it showed a statistically significant reduction in neurotoxicity compared with oxaliplatin - also showed worrying safety and efficacy signals.
Following picoplatin’s failure to show improved survival in a phase III trial for small-cell lung cancer, the news of additional safety and efficacy questions in a second indication does not signal a bright future for the California company (Poniard pays for taking a gamble, November 17, 2009). With just one more indication for picoplatin in clinical trials, no further pipeline products, except an oral version of picoplatin in phase I, and oxaliplatin now subject to generic competition, the likelihood that Poniard will be able to find a partner for picoplatin seem to be fading as fast as its share price, which declined 25% yesterday.
With the poor evidence on picoplatin, analysts have steadily downgraded sales estimates. Just over a year ago EvaluatePharma’s consensus estimate for 2014 sales was $192m. Now it is $38 million, with no anticipated sales revenue for Poniard before 2014.
Poniard ended the third quarter of 2009 with $40m in cash, and it spends about $10m a quarter. To raise money for additional trials, in two separate rounds of financing in November and December it sold seven million shares for $13.9m under a committed equity arrangement with Azimuth Opportunity. At the time of each transaction, the company said it would have enough cash to operate through mid-2010.
With the financial pressure building, Poniard was banking on good news from its clinical trials to secure partners for additional trials and eventual marketing. Bad news does not allow Poniard to negotiate from a position of strength, or, indeed, give it the ability to attract partners at all.
After closing at $2.61 on Friday, Poniard shares fell to $1.95 at the close of trading Monday, and in early trading Tuesday another 10 cents to $1.85.
Presented at the American Society of Clinical Oncology gastrointestinal symposium, the study in 101 metastatic colorectal cancer patients aimed to measure a common first-line treatment protocol, 5-fluorouracil (5-FU), leucovorin, and oxaliplatin, against 5-FU and leucovorin with picoplatin. The patients on the picoplatin regimen fared better on neuropathy; 26% suffered any grade of neuropathy, compared with 62% on the oxaliplatin arm.
However, the efficacy signals were not as clear. Of the patients on the oxaliplatin regimen, 83% survived six months and 55% survived a year, compared with an 80% six-month and a 52% one-year survival rate for the picoplatin patients. Moreover, Poniard said those on picoplatin had more frequent and severe thrombocytopaenia and neutropaenia, along with more frequent alopecia.
The drug has one more shot at delivering a successful set of results with phase II trials ongoing in prostate cancer. However, the omens do not look encouraging in this setting given that a similar platinum compound, satraplatin, failed in phase III prostate cancer trials in 2007, leading to the demise of its lead investigator GPC Biotech (GPC, Pharmion’s phase III failure could raise eyebrows at Poniard, October 31, 2007).
So while Poniard’s leadership may be putting a happy face on the results, without a definitive finding of superiority picoplatin may be another platinum-based therapy headed for the R&D dustbin. As such it would come as little surprise if the company reverts to type in such bleak circumstances and announces a "strategic review", with some shareholder no doubt hopeful that returning cash to them is the best and most logical option.