Separate reports of late-stage data sent two companies' stocks soaring Tuesday, with shares of Theratechnologies Inc. taking the biggest hike, jumping more than 75 percent on news that TH9507 met its primary endpoint in a Phase III study in HIV-associated lipodystrophy.
"The results are just excellent," Theratechnologies President and CEO Yves Rosconi said of the company's TH9507 pivotal study, testing a stabilized analogue of the growth hormone-releasing factor designed to reduce visceral adipose tissue (VAT) in lipodystrophy patients.
Top-line data demonstrated that patients receiving TH9507 achieved a 15 percent VAT reduction vs. baseline and a 20 percent reduction vs. placebo at 26 weeks. The study was powered to detect an 8 percent VAT reduction compared to placebo.
Those results show that TH9507 is "a strong contender" in the space, Rosconi said in a conference call, and has an efficacy and safety profile that "offers great prospects for treatment" with "advantages over other approaches in development."
The company's stock reflected the news. Theratechnologies' shares (TSX:TH) gained C$2.07 Tuesday, or 75.3 percent, to close at C$4.82 (US$4.18).
Patients treated with TH9507 in the study showed an average reduction of 15 percent in VAT, compared to an average 5 percent increase for patients in the placebo arm. The average VAT reduction was 28 square centimeters, with overall body fat lost in the visceral cavity and not clinically significant changes in subcutaneous adipose tissue (SAT) or limb fat.
Importantly, Rosconi said, a subset of glucose-intolerant patients, which made up about 19 percent of the 412-patient trial population, "performed as well as the group as a whole."
Theratechnologies, of Montreal, anticipates reporting 52-week safety data next year, and intends to begin a confirmatory study in the first quarter of 2007. That second Phase III study will follow a similar design as the first, and again will evaluate a reduction in VAT as the primary endpoint. A special protocol assessment was set in August. (See BioWorld Today, Aug. 24, 2006.)
"Our top priority is getting TH9507 to the market as soon as possible," Rosconi said.
HIV-associated lipodystrophy, which is linked to antiretroviral therapies, is characterized by abdominal fat accumulation and often a loss of peripheral subcutaneous fat. It's believed to affect about 250,000 HIV patients in North America and Europe.
There are no approved treatments, though other firms are developing drugs for that indication, most notably Geneva-based Serono SA, which earlier this year filed a supplemental new drug application for Serostim, a recombinant form of human growth hormone. Serostim previously received approval for AIDS wasting.
At this time, Theratechnologies anticipates holding onto North American rights for TH9507, though it does intend to seek a partner. And its recent clinical success, Rosconi said, should "add considerable value to those discussions."
TNFerade Shows Survival Trend
Separately, GenVec Inc.'s stock gained 37 percent on interim survival data from its Phase II/III trial of TNFerade in pancreatic cancer.
As another firm considering its partnership options, Gaithersburg, Md.-based GenVec received a boost following news of interim data from its ongoing pivotal trial of TNFerade in patients with locally advanced pancreatic cancer.
Results for the first 51 patients enrolled in the Phase II/III Pancreas Cancer Clinical Trial with TNFerade (PACT) study showed a 42.5 percent absolute increase in overall survival when TNFerade was added to chemo-radiation, the standard of care, in pancreatic cancer. At one year, survival was 70.5 percent in the TNFerade plus standard-of-care arm vs. 28 percent for patients in the standard-of-care arm.
The news pushed GenVec's stock (NASDAQ:GNVC) up 70 cents Tuesday to close at $2.56.
"We like to think of it as an early holiday gift," said GenVec President and CEO Paul Fischer, adding that the interim data, combined with earlier safety data reported, suggests that TNFerade "has a lot of the hallmarks for being a good product."
Results also "seem to corroborate earlier data from a dose-escalation trial," which showed a clear dose-dependent response of the drug's effect on tumor response and survival, said Mark Thornton, senior vice president of product development for GenVec.
The Phase II/III study is designed to enroll 330 patients to be randomized 2-to-1 to receive chemotherapy and radiation for a five-week period, either with or without TNFerade, an adenovector carrying the gene for tumor necrosis factor-alpha (TNF-alpha). Patients then receive maintenance therapy of gemcitabine and possibly Tarceva (erlotinib, Genentech Inc.) The trial's primary endpoint is survival at 12 months.
GenVec continues enrolling patients. Though it has not disclosed a specific timetable for the study, it suggested that the promising interim data could accelerate development.
The study was powered to achieve a 20 percent reduction in overall survival compared to standard of care. But, with the 42 percent survival benefit shown so far, GenVec is "exploring ways in which the trial can be modified to take into account this finding," Thornton told BioWorld Today.
"If this trend is destined to be real," he added, "we don't want one more patient than necessary to receive an inferior treatment."
TNFerade is designed to work by stimulating production of TNF-alpha, a protein that destroys tumor blood vessels and leads to tumor cell death. The advantage with TNFerade is that "it keeps the protein produced locally in the tumor, so that it's not spilled out into the blood system resulting in toxicity," Thornton said.
Pending positive results from the full PACT study, and armed with safety data accumulated from earlier trials, GenVec expects to have sufficient data to file for regulatory approval.
In the meantime, the company continues discussions with potential partners for ex-U.S. commercialization of TNFerade. In the U.S., however, "we'd like to keep our options open," Fischer said.
GenVec also is studying TNFerade in Phase II studies in rectal cancer and melanoma.
BioMarin Preparing For NDA
More positive late-stage data Tuesday came from BioMarin Pharmaceutical Inc., which confirmed in a Phase III extension study that Phenoptin, its small-molecule drug for phenylketonuria (PKU) met all safety and efficacy endpoints.
Data demonstrated that the drug also showed long-term safety and tolerability as a treatment to control blood phenylalanine (Phe) levels across a range of doses.
Those data came nine months after the Novato, Calif.-based company released its first positive results from Phenoptin's Phase III PKU trial, in which Phenoptin (sapropterin dihydrochloride) demonstrated a reduction at six weeks in blood Phe levels compared to placebo. (See BioWorld Today, March 17, 2006.)
The 22-week open-label extension study enrolled 80 patients, all of whom previously completed dosing in the Phase III study, to receive Phenoptin doses of 5 mg/kg/day, 10 mg/kg/day and 20 mg/kg/day for two-week intervals each, followed by four weeks at 10 mg/kg/day. Findings showed that Phenoptin had a good safety and tolerability profile, which was the study's primary endpoint, and also demonstrated that a once-daily dose regimen of the drug was sufficient to maintain the reduction of blood Phe levels throughout a 24-hour period.
BioMarin said it remains on track to file for approval of Phenoptin for PKU in both the U.S. and Europe in the second and third quarters of 2007, respectively.
Phenoptin is partnered with Serono in the companies' 2005 licensing deal. (See BioWorld Today, May 17, 2005.)