The PharmExec 2005 Pipeline Report - Pharmaceutical Executive

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The PharmExec 2005 Pipeline Report
Dry? Not quite. Instead of 1990s-style blockbusters, pharma's new molecules are niche drugs, cancer treatments and—at last—innovative mechanisms for troublesome targets.


Pharmaceutical Executive


TAK 242 by Takeda

TARGET INDICATION
Septic shock
DEVELOPMENT
Phase III

Designed to compete with Eli Lilly's Xigris (drotrecogin), an expensive, last-resort therapy for septic shock, Takeda Pharmaceutical's TAK 242 was granted fast-track status by FDA in July.

That was the first the US pharma industry heard of the drug. Unlike most domestic drugs, TAK 242 was not monitored closely by clinicians or academic researchers until this year, when it was already in Phase III. Wolters Kluwer's R&DI database has no informational entries before July, and lists no conference presentations and only three research articles, one from the company database and two from journals in Japan, where Takeda is based. IMS also commenced coverage in July, shortly after the FDA announcement.

"It isn't a well-known drug," said one industry insider who asked not to be named. "But the science is very strong and the drug will make serious money."

The new drug inhibits cytokine production and counteracts inflammation by suppressing the signal flow through toll-like receptor 4 (TLR4), which is one of the receptors that recognizes bacterial components, including toxins.

Xigris is a very expensive drug, says Alasdair Conn, MD, chief of emergency medicine at Massachusetts General Hospital, who was not aware of the drug until Pharm Exec called. ( http://Xigris.com/ lists the average wholesale price of the therapy at $6,800.) In 2004, Xigris's worldwide sales rose 26 percent to $201 million, according to Lilly. "If this drug is indeed going head to head with Xigris, that could be a good move," Conn suggests. "Potentially, Lilly could drop the price to keep its market share."

DGJ by NIH

TARGET INDICATION
Fabry's Disease
DEVELOPMENT
Preclinical
PATIENTS IN US
Fewer than 2,000

Fabry's disease patients lack galactosidase, an enzyme that breaks down lipids. Their symptoms range from pain in the extremities to kidney or heart failure and stroke. Therapy is typically enzyme replacement. But if galactosidase is merely folded to code incorrectly for its substrate, injecting 1-deoxy-galactonojirimycin (DGJ), a "molecular chaperone," may correct the problem, says Roscoe Brady, MD, of the National Institutes of Health. The drug helps the enzyme unfold properly and catabolise lipids. "If the enzyme is present," Brady says, "the chaperone can raise levels from five to as much as 30 percent, enough to help the patient."

GW 406381 by GSK

TARGET INDICATION
Acute and chronic pain
DEVELOPMENT
Phase II
LAUNCH DATE
2009
PEAK ANNUAL SALES
$1.5 billion

Were it not for the withdrawal of Vioxx, this second-generation COX-2 inhibitor would be one of the hottest drugs in the pipeline. Early clinical data suggest that the drug will be useful for severe acute and chronic pain, since it has been shown to cross the blood-brain barrier better than existing COX-2 inhibitors.

"There clearly is a need for a non-sedative analgesic without the side effects we see with opiates," says Byron Cryer, MD, professor of medicine at Southwestern Medical School in Dallas, Texas. "We've seen lots of mechanisms that sounded attractive, but really the proof is in the Phase III clinical trials."

Clinical trials are in progress for migraine, rheumatoid arthritis, and osteoarthritis, according to GSK. But even strong clinical data may not be enough to satisfy FDA.

"The threshold for approval has changed," says Cryer, who has published journal articles on second-generation COX-2 inhibitors. "Something that was passed a few years ago may not be allowed to have the same class of evidence for approval now."


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