06 December 1999 00:00 [Source: ICB Americas]By Feliza Mirasol
Pharmacia & Upjohn will further strengthen its oncology portfolio by launching a new anti-breast-cancer drug in the first quarter of 2000. Aromasin (exemestane), a once-daily oral treatment, received Food and Drug Administration approval in mid-October for advanced breast cancer in post-menopausal women. Aromasin was also approved in the UK in June. It is expected to be widely available throughout Europe by mid-2000.
Aromasin is the first aromatase inactivator for the treatment of advanced breast cancer in patients whose tumors stop responding to tamoxifen therapy, says the company. The drug, categorized as a hormonal therapy, interacts with the enzyme aromatase, which is responsible for estrogen synthesis. Researchers believe that by blocking the stimulatory effects of estrogen, the growth and metabolism of breast cancer cells are inhibited.
Unlike other aromatase inhibitors, Aromasin has an irreversible effect, according to P&U. Whereas other aromatase inhibitors bind to the receptor site on the enzyme temporarily, Aromasin remains bound, permanently inactivating that enzyme molecule from synthesizing estrogen.
This is P&U's second approval for a new anti-breast-cancer drug this year. In September, the company received FDA approval for Ellence (epirubicin), which was launched in the US in early October.
Ellence is a chemotherapy agent belonging to a highly active class of drugs known as anthracyclines, an example of which is doxorubicin (Adriamycin). Although it has not been in the US market for long, the drug has been sold globally for nearly 15 years under the name Pharmorubicin. P&U says that through August, Pharmorubicin has had year-to-date sales of $131.9 million outside of the US. Analysts project total 1999 sales of Pharmorubicin at roughly $200 million and estimate that total sales of the drug, both US and international, will reach roughly $235 million next year.
The company says that Ellence, which was approved in the US as a component of adjuvant therapy for treating primary breast cancer, is the first chemotherapy agent approved for the treatment of early node-positive breast cancer following surgery. Like other anthracyclines, Ellence has cytotoxic properties against many types of tumors, although its exact mechanism of action is not completely understood. Anthracyclines are commonly used in combination with other medications to treat cancer patients.
P&U says Ellence may also be a better alternative to a currently used adjuvant therapy, CMF (cyclophosphamide, metho- trexate, fluorouracil), because it offers a greater reduction of the risk of death (29 percent reduction) and the risk of cancer recurrence (24 percent reduction) than CMF. In addition, Ellence appears to be at least as active but less toxic than doxorubicin, one of the most commonly used anthracyclines in the US.
Both Aromasin and Ellence are expected to be priced competitively against other anti-breast-cancer treatments. "In terms of the cost for [the drugs], they're going to be comparable with other drugs that are used similarly," the company says.
Among the older anti-breast-cancer drugs is tamoxifen (Zeneca Pharmaceutical's Nolvadex). Tamoxifen is among the first round of chemopreventive agents to receive FDA clearance (October 1998) for reducing the incidence of breast cancer in women at high risk for the disease. The drug has been used in the treatment of breast cancer for more than 20 years, says FDA. Year-to-date September sales of tamoxifen reached $203 million, according to estimates by IMS Health.
Tamoxifen is thought to act as an anti-estrogen, competitively binding to receptors in the nuclei of some breast cancer cells, thereby inhibiting the binding of estrogen itself. Other indications suggest that tamoxifen may also block the growth of breast cancer cells by decreasing the secretion of transforming factor-alpha, which stimulates tumor growth, and increasing the secretion of the beta form of that substance, which inhibits tumor growth. Tamoxifen may also increase the body's level of natural killer cells, which break down a range of tumors.
Waltham, Mass.-based Decision Resources Inc. says that in addition to tamoxifen, other agents are being considered for the potential chemoprevention of breast cancer. Among these candidates are fenretinide, other retinoic acid derivatives and Eli Lilly & Co.'s Evista (raloxifene).
Other drugs currently on the market for breast cancer include the cytotoxic agents cyclophosphamide, methotrexate, 5-fluorouracil, vinblastine, thiotepa, fluoxymesterone and paclitaxel.
Among the newer breast cancer agents are Genentech Inc.'s Herceptin (trastu-zumab), approved in September 1998, an innovative product resulting from monoclonal antibody technology, and Hoffmann-La Roche's Xeloda (capecitabine), an oral treatment approved in April 1998 for advanced cases.
Decision Resources projects that by 2007, breast cancer therapeutics in the seven major markets will total almost $3 billion, with tamoxifen and paclitaxel continuing to dominate.
ALEXION Pharmaceuticals Inc., New Haven, Conn., has sold an additional 415,000 shares of common stock to the underwriters of its recently completed public offering, raising the total from the offering to $47.8 million. These funds will be used to finance clinical and manufacturing development of 5 G1.1 for the treatment of acute inflammation. In addition, they will fund pre-clinical research, drug discovery programs and clinical manufacturing development for the company's other programs.
ASPIRIN COMBINATION--FDA has approved a new drug that combines the active ingredients aspirin and dipyridamole into one pill. The new drug is for the reduction of the risk of strokes in patients who have already had transient ischemic attacks or completed ischemic strokes due to blood clots in the brain. It will be marketed as Aggrenox by Boehringer Ingelheim Pharmaceuticals Inc.
GAMMA HYDROXYBUTYRATE--The US Senate has approved legislation (S 1561) directing the Attorney General to make illicitly manufactured gamma hydroxybutyrate (GHB) an illegal substance, while making Orphan Medical Inc.'s medically formulated GHB product, Xyrem (sodium oxybate) oral solution, available to treat patients with narcolepsy.
HERBAL EXTRACT--PL Thomas & Co. Inc. now offers a range of excipient-free standardized herbal extracts, derived purely from the herb by which each extract is identified. The company's products include black cohosh, chaste tree, Panax and Siberian ginseng, grape seed and olive leaf.
PVP-IODINE--International Specialty Products will increase its prices for povidone-iodine, effective January 1, 2000. Bulk and truckload drum prices will be raised by 5.5 percent. The company says that the increase will help support investments being made to increase the capacity of its Calvert City, Ky., plant.
TACROLIMUS--Food and Drug Administration has accepted Fujisawa Healthcare Inc.'s new drug application for tacro-limus ointment, for atopic dermatitis.
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