West Coast Editor
Already less hurt than others involved in the satraplatin trouble, Spectrum Pharmaceuticals Inc. might have taken some of the edge off bad news on that drug by signing a license agreement with Milan, Italy-based Indena SpA for the third-generation taxane known as ortataxel, which has completed Phase II trials.
But satraplatin licensee Spectrum still took its licks on Wall Street, along with developer GPC Biotech Inc. and GPC's partner Pharmion Inc., when trading resumed after an unfavorable FDA advisory panel vote.
The Oncology Drugs Advisory Committee decided 12-0 to recommend that the agency wait for the overall survival results from the pivotal trial with satraplatin - conducted under a special protocol assessment deal - rather than accept progression-free survival data by themselves. (See BioWorld Today, July 25, 2007.)
"It was a blowout," said analyst Stephen Dunn with Dawson James. Satraplatin "didn't stand a chance," he told BioWorld Today, though another watcher of the panel meeting, Ren Benjamin with Rodman & Renshaw, at one point called the odds 50-50.
Irvine, Calif.-based Spectrum's shares (NASDAQ:SPPI) closed Wednesday at $3.96, down 84 cents, or 17.5 percent. Stock value for GPC (NASDAQ:GPCB) tumbled 35.4 percent to $13.16, down $7.20. Pharmion Corp. (NASDAQ:PHRM) ended the day at $24.24, down 38 cents.
A public alert regarding the trouble with satraplatin came last week, when the FDA published briefing documents on its website.
Those documents concluded that, "based on a review of background materials provided by the applicant describing the methods for assessing pain intensity in the [pivotal] SPARC Study, the single item Present Pain Intensity Scale (PPI), derived from the McGill Pain Questionnaire, has not been adequately validated for use" in SPARC.
During a wee-hours (U.S. time) conference call, officials from Martinsried, Germany-based GPC faced questions about how much the company knew, and when. Thomas McKearn, GPC's vice president of medical affairs, noted that the original protocol did not include the PPI, which was put in after the FDA suggested it.
No further discussions were had with the agency since that decision was made. "What has happened in the interim, and this happened in February 2006 - that is to say, one month after the last patient was enrolled in the [pivotal] SPARC trial - [was] that the FDA published draft guidance," McKearn said. This was the "patient-related outcomes" document that formed the basis for some ODAC skepticism regarding the SPARC results.
News that regulators had questions about the way the pain part of the progression-free survival endpoint would be implemented "came to us, as it came to you folks, in the briefing documents," McKearn said. "We had not heard any feedback along those lines at earlier points in our interactions with the review staff."
Not even the SPA was enough to save GPC from the surprise.
"An integral part, and really the final piece of the SPA implementation, if you will, is to review after submission of the NDA the applicability of all of these pieces, in the case of this composite endpoint - and pain in particular," McKearn said. "The FDA, explicitly by statute, [has] the right to wait until the review process to finalize their acceptance of all of these components," even if the parts were "provisionally accepted" at the time the trial started.
Satraplatin's PDUFA date is Aug. 15. The FDA could issue an "approvable" letter, with clearance pending the overall survival data, as ODAC recommended. Or the agency could issue a "not-approvable" letter, which means GPC would have to re-file when the overall survival data become available. Another option is that the FDA could overrule ODAC and approve satraplatin, though analysts see this as unlikely.
Bernd R. Seizinger, GPC's CEO, pointed to "inherent unpredictabilities" in the timing of final survival results, which depend on the death rates - slowing, at last report, a phenomenon "not unusual toward the end of such a study."
He estimated the data might be available in about six months, "a few months later than we anticipated," and forecast a 12-month time frame for a potential FDA approval.
Analyst Benjamin agreed, writing in a research report Wednesday that "a second bite at the apple will take time," since deaths are down to five per month. "In our opinion, based on the current trend, the survival results will likely become available by the first half of 2008," he wrote.
Seizinger reminded listeners on the conference call that GPC ended the first quarter with about $150 million in cash and cash equivalents, easily enough to take the company to the point where full survival results become available.
Spectrum, meanwhile, has its deal with Indena for ortataxel. Like satraplatin, it's an oral cancer compound, and Spectrum took worldwide rights in exchange for an undisclosed up-front payment plus regulatory and sales milestones, as well as royalties if the drug wins approval.
Ortataxel is designated a new chemical entity, and has shown activity in taxane-refractory tumors in Phase II trials, Spectrum said.