By Jim Shrine
The FDA granted accelerated approval to Alza Corp.'s Doxil for refractory ovarian cancer, marking the first liposomal drug approved to treat a solid tumor.
The drug, a liposomal formulation of doxorubicin, also was the first from that class approved for any indication when the agency cleared Doxil in 1995 to treat Kaposi's sarcoma (KS). The drug was developed by Sequus Pharmaceutical Co., and Alza completed its acquisition of Sequus in March.
Sales of Doxil in 1998 were $42.2 million, most from off-label uses, since the KS market has dwindled over the years because of more effective HIV drugs. The new approval will allow Alza and its 110-person sales group to market Doxil for treating ovarian cancer that is refractory to paclitaxel and platinum-based chemotherapy regimens.
"The fact that we will be able now to promote the product in the ovarian cancer setting will have a positive impact on sales," Alza spokeswoman Anneke Cole said. "This enables Alza and our sales organization to start educating people on how to use Doxil in that setting, which is different than KS."
The approval - and that of Ethyol last week for reducing dry mouth associated with radiation treatments for cancer - helps fill out Alza Oncology, a group formed earlier this year to focus on the cancer market. Both drugs, which have been on the market for years, were recommended for approval for the new indications by the FDA's Oncologic Drugs Advisory Committee three weeks ago. (See BioWorld Today, June 9, 1999, p. 1.)
Alza gained U.S. rights to Ethyol from U.S. Bioscience Inc., of West Conshohocken, Pa. Alza's focus for Doxil also will be in the U.S. They are the flagship products in Alza's new oncology business.
Cole said the FDA granted orphan status to Doxil for this indication, meaning no other liposomal agent for refractory ovarian cancer can be marketed for seven years.
"Our priority and focus is on launching Ethyol and Doxil for their respective new indication in the U.S.," Cole said.
Schering-Plough Corp., of Madison, N.J., has Doxil rights in Europe. It is expected to seek approval of Doxil there this year for treating metastatic breast cancer, Cole said. After that, Alza would be expected to use results from the breast cancer studies to support filing in that indication in the U.S. That filing is targeted for sometime in 2000, Cole said.
"It's certainly been a busy week and a half," Cole said, noting the company's acquisition by Abbott Laboratories, of Abbott Park, Ill., in addition to the expanded labeling of the two products. "It's been very exciting for Alza, particularly on the oncology side," Cole said. "We've really made an effort over the past couple of years to bolster our place in oncology."
Alza, of Palo Alto, Calif., now has one of the six largest specialized oncology sales forces in the U.S., Cole said.
"For a company Alza's size that pretty significant," she said. "That's one of the reasons the Abbott acquisition made so much sense for both companies. Abbott has a strong pipeline of products for oncology but doesn't have a presence in oncology yet. With Alza, they're acquiring a company with a solid presence in oncology already, including a specialized sales force."
Abbott agreed to acquire Alza, of Palo Alto, Calif., last week in a stock deal worth about $7.3 billion. (See BioWorld Today, June 23, 1999, p. 1.)
The Doxil approval came through the FDA's accelerated process, which allows approval on surrogate endpoints - tumor response rates, in this case - on the condition that the company demonstrate the drug's clinical benefit in post-market studies. The FDA is allowing Alza to use its ongoing Phase III trial to satisfy that requirement, Cole said.
The Phase III study, comparing Doxil to the chemotherapy agent topotecan, already is fully enrolled, Cole said, and results are expected in the first half of next year.
Doxil uses what Sequus called Stealth technology to evade recognition and uptake by the immune system, allowing it to circulate longer and increasing the chance the encapsulated drug will reach its tumor target. The technology uses a fatty coating called polyethylene glycol liposome as the delivery mechanism.
Data from the three Phase II trials and some early Phase III results showed Doxil produced a response rate of 14.4 percent in metastatic ovarian cancer, with response defined as a reduction of at least 50 percent in tumor size.