About four months after Human Genome Sciences Inc.'s repifermin failed in a Phase II trial against venous ulcers, the drug fizzled in another Phase II study that was testing it as a treatment for mucositis induced by cancer therapy.
Wall Street apparently was not surprised. The company's stock (NASDAQ:HGSI) dipped only 33 cents on the news, closing at $13.74.
Repifermin (keratinocyte growth factor-2), a human protein discovered by HGS, will not be developed further for any indication.
Jerry Parrott, vice president of corporate communications for Rockville, Md.-based HGS, told BioWorld Today the outcome of the first Phase II trial was "not particularly" useful in surmising the outcome of the second.
"One was topically administered - in the wound-healing indication - and the other one is systemically administered," he pointed out.
Nor was it an indicator of success when Thousand Oaks, Calif.-based Amgen Inc. scored with positive Phase III preliminary data in June from its recombinant human keratinocyte growth factor, palifermin, against mucositis related to cancer therapy.
"They're similar targets, but the reality is that every drug is different," Parrott said. "As a scientist here once said to me, you don't know until you know, until you do the trials and have the data."
Efficacy in the Phase II trial with repifermin against mucositis was measured as the percentage of patients experiencing Grade II-Grade IV mucositis at the highest dose of drug given. The study was designed to show a 40 percent relative reduction, but the percentage of patients treated with the highest dose - 75 mcg/kg - showed Grade II-Grade IV disease that was not statistically significantly different from placebo.
Ninety-two patients with multiple myeloma, who were scheduled to get two autologous hematopoietic stem cell transplantations, were randomized in the single-center, double-blind, crossover, dose-escalation Phase II trial.
Of those, 51 patients were given either placebo or repifermin at the 75 mcg/kg dose intravenously daily for three days before their chemotherapeutic conditioning regimen, and daily for seven days following their first autologous hematopoietic stem cell transplantation.
After a period of three months to six months, patients who had been administered repifermin for their first transplantation were given placebo before and after their second transplantation. Patients who had received placebo for their first procedure were administered repifermin before and after their second. The drug was well tolerated across all doses with a safety profile similar to placebo.
Alice von Loesecke, senior director of the intelligence unit for research firm Decision Resources, said a survey of 83 oncologists in the U.S. last April and May found them eager for any safe treatment that works.
"Right now, there is nothing," she told BioWorld Today. "A lot of them are using ice chips, cryotherapy in the mouth as you give the infusion. It reduces blood flow to the mouth so they don't get as much chemotherapy in the area."
That doesn't work spectacularly well, nor does the so-called "magic mouthwash," which contains pain relievers and a liquid coating for the mouth, throat and esophagus, she said.
"If you get very severe mucositis, you're way beyond that," she said.
Physicians were enthusiastic about the Amgen treatment even before Phase III data were unveiled in June, and the HGS drug "was the closest one behind it."
HGS has no other growth factors like repifermin in its basket, Parrott said, but the company's remaining drug candidates are making progress.
"We've still got a very rich pipeline," he said. Last month, the company began dosing patients in a Phase II trial of LymphoStat-B (human monoclonal antibody to B-lymphocyte stimulator, BlyS) for rheumatoid arthritis. The trial will evaluate LymphoStat-B in about 230 patients with active rheumatoid arthritis who have failed prior therapy. Positive Phase I data support developing the drug for lupus, too.
"Moving along very nicely in a variety of Phase I trials" are the Tumor Necrosis Factor Apoptosis-Inducing Ligand (TRAIL) Receptor-1 and TRAIL Receptor-2 proteins, he said.
In October, HGS entered a license agreement with DiaDexus Inc., of South San Francisco, giving HGS exclusive, worldwide rights to develop and commercialize diagnostic immunohistochemical tests based on the proteins, which HGS discovered. DiaDexus, which had gained diagnostic rights through a deal with London-based GlaxoSmithKline plc, retains exclusive commercial rights for diagnostics in other formats.
HGS also has Albuferon-alpha for hepatitis C. At the annual meeting of the American Association for the Study of Liver Diseases in Boston last fall, the company offered interim results from an ongoing Phase I/II trial with the drug, showing it to be well tolerated, with a prolonged half-life and biological activity in treatment-experienced adults with chronic HCV.
"We have enough to keep us busy," Parrott said.