West Coast Editor

SAN FRANCISCO - After days of rain that flooded parts of the Bay Area, the sun shone like Biblical hope on JPMorgan's 24th Annual Healthcare Conference here, with about 7,000 attendees expected and 296 companies showing their stuff to investors.

Dark clouds broke somewhat more for multiple myeloma patients, too, on word that Celgene Corp.'s Phase III study with its approved drug Thalomid (thalidomide) - which already has a supplemental new drug application for the blood cancer pending with the FDA - met a pre-established efficacy goal of p<0.0015 for the primary endpoint, time to disease progression. Results with Thalomid and its derivative, Revlimid, have been "unprecedented," said Brian Gill, director of public relations for Warren, N.J.-based Celgene. "There's nothing else like it." His firm was among those presenting Monday morning at the JPMorgan event.

Celgene's stock (NASDAQ:CELG) ended the day at $71.88, up $3.05.

The favorable news on Thalomid, which adds to a growing stack of data, means treatment assignments for patients on the trials will be unblinded and those not getting the drug will have the chance to add it to their dexamethasone regimen.

Results are confirmatory, so they will not become part of the sNDA waiting action by regulators, "but they're certainly aware of it," Gill said.

Specifically, an independent data monitoring committee found that the trial, testing the approved leprosy drug Thalomid (already widely used off label for MM) in combination with dexamethasone as compared to dexamethasone alone as induction therapy for previously untreated MM, yielded time to disease progression of 75.7 weeks vs. 27.9 weeks (p=0.000065).

Progression-free survival totaled 55.7 weeks vs. 24.3 weeks (p=0.0003) in patients who got Thalomid as opposed to those given only dexamethasone alone.

Conducted under a special protocol assessment, the randomized, placebo-controlled study included 270 patients randomized to get thalidomide plus dexamethasone, or placebo plus dexamethasone. Researchers calculated time to disease progression by counting from the time from randomization to the first finding of progressive disease based on Bladé myeloma response criteria.

Patients given the Thalomid and dexamethasone combo showed an increase in side effects as compared to those given placebo plus dexamethasone alone. They included insomnia, tremors, dizziness, peripheral neuropathy and constipation. Grade 3 or Grade 4 adverse events reported included deep-vein thrombosis (DVT), occurring in 10.3 percent of patients treated with thalidomide plus dexamethasone, compared to 1.7 percent of patients treated with placebo plus dexamethasone alone.

Pulmonary embolism occurred in 5.6 percent of patients treated with thalidomide plus dexamethasone, compared to 1.7 percent of patients treated with placebo plus dexamethasone alone.

MM, also known as myeloma or plasma cell myeloma, is a blood cancer in which malignant plasma cells are overproduced in the bone marrow. Celgene also has Revlimid (lenalidomide), which gained FDA clearance in late December for myelodysplastic syndromes. A supplemental NDA filing is expected shortly, seeking the go-ahead for that compound to officially target multiple myeloma. (See BioWorld Today, Dec. 29, 2005.)

A third star on the MM front is Velcade (bortezomib), from Millennium Pharmaceuticals Inc., of Cambridge, Mass., which recently yielded data from trials testing Velcade alone or in combination with other commonly used agents in previously untreated MM, and gained overall response rates as high as 92 percent, with complete response rates as high as 30 percent.

"Some thought leaders are convinced that MM [eventually] will be treated like a chronic disease, with a cyclical treatment regimen," Gill told BioWorld Today. "It's an incurable disease. How can any drug compete with another in a situation like that?"

Life expectancy, previously about three years after diagnosis, has been extended, though, by about five years to seven years. Annually, 15,000 new cases of MM are reported in the U.S., and at any one time, between 60,000 and 70,000 patients are living with the disease, said Brian Durie, chairman of the International Myeloma Foundation in North Hollywood, Calif., who has been involved in research with Thalomid, Revlimid and Velcade.

"Each of them is going to have its place," he said, since each brings advantages and disadvantages. Revlimid does not cause neuropathy, giving it an advantage over Thalidomide. Velcade appears not to cause DVT, but it's intravenous rather than oral.

"Thalidomide, for all its faults, still has an important place in myeloma, since it does not knock down the blood count and put the patient at risk of infection," he added.

That drug also was a "critical triggering factor" in MM experiments, which have picked up in recent years, Durie told BioWorld Today.

"Celgene kind of backed into that one," he said. "They were very fortunate it turned out to be so active in myeloma. That brought a lot of focus, a lot of money into the research. It also showed that a targeted biologic approach in myeloma could work, so when Velcade came along, there was a lot more confidence about throwing that into the mix."

Physicians will continue to combine novel agents with standard therapies such as the alkylating agents, Durie said. On the horizon for MM is the heat-shock protein 90 inhibitor IPI-504, from Infinity Pharmaceuticals Inc., of Cambridge, Mass., which has the product in a Phase I study in relapsed or relapsed/refractory multiple myeloma. It is expected to announce today that it is initiating a second Phase I trial to evaluate the drug in patients with gastrointestinal stromal tumors (GIST) that are resistant to Gleevec (imatinib mesylate, by Novartis AG).

"People are kind of hooked on the NFkB pathway now," Gill said. "They seem to feel that if you can block it in a couple of places, or maybe block one of the natural escape pathways, which is what the heat-shock protein does, that could work." NFkB is a transcriptional activator implicated in cancer and inflammatory diseases.

The JPMorgan conference, long considered a first-of-year bellwether, brought the customary packed hallways to the Westin St. Francis Hotel. Registration began Sunday afternoon, and by early evening, the streets of Union Square teemed with people carrying bright red canvas bags given during sign-in. The meeting continues through Thursday.