The PharmExec 2005 Pipeline Report - Pharmaceutical Executive


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

Panzem [2-methoxyestradiol], from Entremed, is a naturally occurring metabolite of estradiol, a type of estrogen. Currently in Phase II trials for prostate cancer and age-related macular degeneration, the drug was developed by one of Folkman's colleagues at Children's Hospital.

PCK 3145, by Procyon, is a synthetic peptide based on a prostate protein (PSP 94), which has anti-VEGF effects. The compound is currently in Phase II trials for prostate cancer.

Thalidomide, by Celgene, is one of the most prescribed anti-angiogenic agents in the world, if only outside the United States. Thalidomide is widely prescribed for leprosy and multiple myeloma, among other maladies. (See separate profile.)

Revlimid, by Celgene, is more potent than thalidomide, but has fewer side effects. It offers new hope for patients with resistant forms of multiple myeloma. (See separate profile.)

Zactima [vandetanib], by AstraZeneca, inhibits vascular endothelial growth factor receptor-2 (VEGFR-2). It is an orally administered anti-angiogenic agent in Phase II and III clinical trials for various solid tumors, including lung, thyroid, and breast cancer, as well as multiple myeloma.

Torcetrapib with Lipitor [atorvastatin] by Pfizer

Phase III

Torcetrapib began life as a stand-alone treatment for atherosclerosis. But in the course of clinical trials, Pfizer discovered that the ester transfer protein antagonist raised levels of high-density lipids (HDL), the blood component often referred to as "good cholesterol." For the past several years, Pfizer has said little about torcetrapib as a stand-alone therapy.

Instead, the company has pushed a program to market torcetrapib as a fixed-combination cholesterol therapy with Lipitor, the top-selling drug in the world. Many analysts like the idea. If successful, the combination therapy has blockbuster potential because patients would be able to raise HDL and lower LDL, or "bad cholesterol," with one pill. The proposed formulation is 40 mg of Lipitor, with 60 mg of torcetrapib.

"There are people who would suggest that they are doing that to carry on the monopoly with Lipitor," says Ryan, noting that Lipitor faces patent expiration in 2010. "But the HDL theory may not be as well-established as the LDL theory," she says. "And HDL may be more complicated in terms of what kinds of HDL matter, and how high is high. At the end of the day, if raising HDL doesn't provide any benefit, then the combination is not compelling."

Thalomid [thalidomide] by Celgene

Revlimid [lenalidomide] by Celgene

Multiple myeloma
Phase III

Murray Aitken
Best known for causing birth defects when boomers were babies, thalidomide is making a comeback in the United States as an oncology drug. The once notorious compound is in pre-registration for multiple myeloma, a bone-marrow tumor, and in Phase III trials for indications ranging from myelodisplastic syndrome (MDS) to colorectal, lung, and renal cancers.

"Thalidomide has been a successful treatment for multiple myeloma throughout the world for the last four or five years," says Folkman of Harvard. "Now it's moving into solid tumors as an angiogenesis inhibitor. There is a report [from Celgene] that adding thalidomide to topotecan, a chemotherapy agent, is very good for ovarian cancer."

Revlimid, a derivative by Celgene that Folkman calls "the son of thalidomide," is nearing FDA approval for myelosdisplastic syndrome and multiple myeloma. An immunomodulating agent with anti-angiogenic properties, the drug appears to act directly on multiple myeloma cells that are resistant to common forms of chemotherapy.


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