Patricia F. Fitzpatrick Dimond Ph.D. Technical Editor of Clinical OMICs President of BioInsight Communications

Disappointing Phase III results in SCLC but promising Phase II results in colorectal cancer make company’s future uncertain.

There was more disappointing news for cancer patients and doctors treating small-cell lung cancer (SCLC) as Poniard Pharmaceuticals, formerly known as NeoRx, announced on November 16 that its pivotal Phase III SPEAR trial of picoplatin in the second-line treatment of SCLC failed to meet its overall survival primary endpoint.

Poniard says that the SCLC trial failed because more patients on the best supportive care arm received chemotherapy following disease progression than those on the picoplatin arm, meaning survival was better in the control arm than anticipated. The company is awaiting further data in January.

Picoplatin is in development as a treatment for SCLC, colorectal cancer, and prostate cancer. It reportedly has an improved safety profile compared to existing platinum-based chemotherapeutics to overcome platinum-resistance associated with chemotherapy in solid tumors and delay time to relapse. Severe toxicities associated with most current platinum-based drugs include neuropathies, renal toxicity, and myelosuppression.

On news of the trial results, the company’s stock declined a breathtaking 78%, but then recovered as much as 36% as the company announced, on November 17, that picoplatin showed comparable efficacy to an already approved treatment, oxaliplatin, in a Phase II mid-stage colorectal cancer study. The company also announced new results from its Phase I cardiac safety trial, which showed no picoplatin clinical cardiac-related events.

According to Jerry McMahon, Ph.D., CEO, “Our updated proof-of-concept Phase II safety and efficacy results continue to suggest that picoplatin could be superior to oxaliplatin as a neuropathy-sparing alternative when used in combination as a first-line treatment for metastatic colorectal cancer.” The company is continuing follow-up on patients to obtain median overall survival data to facilitate an end of Phase II meeting with the U.S. FDA.

The study results showed that the drug, given once every four weeks in combination with 5-fluorouracil and leucovorin in the FOLPI regimen, has comparable efficacy to oxaliplatin, given in combination with 5-fluorouracil and leucovorin in the modified FOLFOX-6 regimen, as assessed by one-year survival rate, progression-free survival, and disease control.

If the SCLC trial top-line results had been positive, the company intended to initiate rolling submission of an NDA with the FDA by year-end, Dr. McMahon said, targeting approval and commercial launch of picoplatin in 2010.

Poniard had also planned to continue exploring potential development and commercialization partnerships for picoplatin but is currently burning through $10 million a quarter, and as of September 30 was  down to $40.1 million in cash and investment securities. In March, the cash-strapped company initiated a restructuring resulting in discontinuation of all of its preclinical research activities and release of 12% of its workforce (eight employees).  That same month, Pionard’s auditors presented the company with a going-concern warning.  

Still Banking on Picoplatin

At this point, Poniard appears to be dependent on Phase II results with its only drug candidate to find a partner. “Based on the current data in colorectal cancer, as well as encouraging efficacy and safety data from more than 1,100 cancer patients treated with picoplatin in clinical trials, including the cardiac safety trial data, we are continuing discussions with potential partners,” Dr. McMahon said. But analysts remain skeptical regarding the drug’s utility in lung cancer. “The likelihood for this drug ever winning approval in SCLC in slim to none, in our view,” wrote Canaccord Adams’ analyst George Farmer, Ph.D.  

Before cutting out its preclinical research program during a cash-conserving reorganization last year, Poniard had been thinking beyond picoplatin. The company licensed a class of protein kinase inhibitors for treating a variety of diseases from Scripps Research Institute. The candidates were discovered through a research collaboration supported by Poniard. “We are pleased with the productive collaboration with Scripps Research,” Dr. McMahon said in a statement issued at the time. “We are on target with our program at Poniard to identify a kinase drug candidate that has the potential to be combined with our lead product picoplatin.”

But while Poniard might eventually have developed a kinase inhibitor pipeline, and the CEO was more than well-qualified to shepherd the development of protein kinase inhibitor drugs, he was hired to develop picoplatin, according to Dr. Farmer. Prior to his job at Poniard, Dr. McMahon was president and head of research at Sugen, where he was a co-developer of Sutent, a small molecule multitargeted kinase inhibitor and the only drug ever to gain simultaneous FDA approval for two types of cancer. 

Poniard’s fortunes may, however, rise and fall on picoplatin. Despite the clinical trial results in SCLC, Dr. Farmer thinks that “picoplatin has potential in other diseases, and the drug can be a better oxaliplatin. But developing it is going to require the right partner and finding that partner will be difficult given Poniard’s current financial situation. Even though Poniard has a credit facility in place, I can see a potential partner dragging it out. The company should have planned for the worst case.”

On November 23, Poniard sold 3,465,878 of its common shares to Azimuth Opportunity for gross proceeds of approximately $7.4 million. The company plans to use the $7.3 million in net proceeds from this sale to focus on regulatory and partnering activities for picoplatin, clinical development, other general corporate purposes, and working capital.

Patricia F. Dimond, Ph.D., is a principal at BioInsight Consulting. Email: [email protected].

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