The granddaddy of all cancer meetings - of all scientific meetings, many agree - came and went earlier this year, when the American Society of Clinical Oncology held its annual convergence in Chicago.
But the beat went on last week in Washington, where the American Association for Cancer Research held its 94th annual meeting. Hardly yielding the headlines ASCO did, AACR offered up its own stream of developments, mostly early stage.
"By comparison, the AACR [meeting] is almost boring," said Lewis Metts, president and CEO of Taxolog Inc. "You have so many people doing so much mechanistic work, which is far back in the iffy' stuff. Many of them are trying to explain how old drugs work. Our poster sort of stood out, because there weren't many new drugs presented."
Taxolog, a Fairfield, N.J.-based company of 36 employees founded in 1997 by Metts, lately found itself "standing out" in other ways, embroiled in legal skirmishing that put the firm in the spotlight. The AACR meeting came just in time to give Taxolog some favorable public exposure.
Metts' company is developing a novel taxane jointly with Wyeth Research (a division of the pharmaceutical firm Wyeth, formerly American Home Products Corp.). The compound is said to inhibit the growth of tumor cell lines resistant to Taxol (paclitaxel) and its first developed analogue, Taxotere (docetaxel).
Under the terms of the deal, Wyeth has "exclusive rights for indications in oncology for three years - one more year," Metts said.
Taxol was first approved in the U.S. for refractory ovarian cancer in 1993 and was launched the following year by Bristol-Myers Squibb Co. The compound from Wyeth and Taxolog, named MAC-321, is "in the same class as Taxol and Taxotere [sold by Aventis SA], but the preclinical efficacy in animals, specifically mice, is far greater than the prototypic taxanes. It's far different also in that it's orally active," Metts said.
Like the other two drugs, MAC-321 has been found to boost the rate of tubulin polymerization in vitro and cause the bundling of microtubules in cells, which represses normal reorganization of the microtubule network and halts cell division.
But preclinical studies "suggest there are many tumors that Taxol or Taxotere won't touch and that, at least in mice, our drug will cure," Metts said. Wyeth and Taxolog tested MAC-321 in resistant cell lines grown in vitro and in vivo.
One 70 mg/kg intravenous dose of MAC-321 eliminated detection of tumors that were partially responsive to a single dose of Taxol, and either partially or completely inhibited tumor growth in three tumor models resistant to Taxol, said an abstract presented at the AACR meeting.
MAC-321's intravenous formulation is in a Phase II trial that is "just getting started," and the oral formulation is in Phase I. Development of the drug, though, has been fraught with strife never sought, or expected, by Taxolog, Metts told BioWorld Financial Watch.
A U.S. Court of Appeals ruling earlier this month found that American BioScience Inc. (previously known as VivoRx Inc.), the privately held parent company of American Pharmaceutical Partners Inc., owns the patent on three next-generation taxane anticancer compounds (called the '653 patent). That ruling overturned a lower court decision in a lawsuit filed in 1998 by Florida State University and Taxolog, claiming they were the true inventors of the compounds.
"There was [an alleged] theft of trade secrets from Florida State," Metts said. ABI paid $300,000 in June 2001, but the payment didn't settle the matter of patent ownership.
"We went on to claim the patent they had was invalid, and that some of the Florida State people should have been named as authors," he said.
This was the case decided by the appeals court - in favor of ABI.
"As far as we're concerned, it's settled," Metts added, although FSU may ask for a re-hearing.
Metts said he was involved in talks with ABI over what the amount due from ABI should be, and was "really disturbed" that Taxolog ended up in that position. "I said, Just the fact that we have to deal with you . . . damages us,'" he recalled saying in a meeting.
FSU had said the compound was worth more than $200 million, and claimed that two of its professors should have been named as inventors in the patent, charging that three ABI researchers should not have been.
After a two-week trial, an appeals judge ruled that "there is no evidence that FSU's inventors conceived of any of the claimed compounds," pointing out that to have in mind "specific portions of a claimed compound is not the same as conceiving the compound with all of its components."
ABI marches on with taxane-related research, and to notable success.
The company of which it's the parent - American Pharmaceutical Partners - offered positive data at the ASCO meeting earlier this year from the first 28 of 100 patients enrolled in a Phase II, metastatic breast cancer trial of ABI-007, a novel cremophor-free protein-engineered nanoparticle version of paclitaxel. Patients were eligible for the trial if they had metastatic breast cancer and had shown ongoing growth of their tumor even after receiving Taxol or Taxotere.
After getting ABI-007 weekly, five of the 28 patients (18 percent) showed a reduction in tumor size of at least 50 percent, with duration of response ranging from six months to more than 10 months, despite the patients' demonstrated resistance to current taxane therapy.
Six of the 28 (21 percent) of those patients remained progression-free for more than eight months, with two progression-free for more than 10 months. All six patients remained in the ongoing study, receiving weekly doses of ABI-007.
American Pharmaceutical Partners, which chalked up $81.34 million in sales in the first quarter of this year, is expected to report second quarter earnings Thursday. The company is valued strongly on its injectable generic drugs.
Meanwhile, parent company ABI scored another legal victory recently. The Superior Court of California in Los Angeles dismissed a claim by third-party payers that ABI and Bristol-Myers had conspired to delay the release of generic Taxol. IVAX Corp. has the generic version, called Taxene.
Taxolog, thankfully, is not involved in that matter at all, Metts said.
"We don't want anything to do with ABI," he said.