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
Torcetrapib with Lipitor [atorvastatin] by Pfizer
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
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.