By Don Long
Maxia Pharmaceuticals Inc. launched a Phase III trial of its MX6 product to treat intermediate- to high-grade cervical intraepithelia neoplasia (CIN II-III), a precancerous condition which, if untreated, may progress to cervical cancer.
The multicenter trial follows successful results from a recently completed Phase I/II trial, in which MX6 "cured or improved the status of about one-half of all patients treated and [it] was well tolerated," according to Magnus Pfahl, president and CEO of the San Diego-based firm.
MX6 incorporates a new class of chemicals called retinoid-related molecules (RRMs), shown to selectively target and kill a range of cancers in laboratory and animal models. The Phase III trial is being carried out under a new drug application that has been granted priority review by the FDA.
"The FDA is very excited about this," Pfahl told BioWorld Today, "because the condition can only be treated by various types of surgeries and they can all have side effects." Up to a quarter of such surgeries may result in serious complications, Pfahl said.
MX6 has been developed as a gel that is applied topically, via timed release.
CIN is diagnosed primarily through an abnormal Pap smear, followed by a colposcopy and biopsy. More than two million women each year are diagnosed with various grades of CIN, and about 700,000 of these cases are classified as CIN II-III.
Maxia's Phase III trial will follow 140 women at six clinical U.S. sites, comparing the status of patients using MX6 with those using a placebo over a 14-day period. The company is also preparing to launch another Phase III trial in Britain, Pfahl said. These trials will be evaluated in 1999, and the company is hoping for FDA approval sometime in the year 2000.
A molecular biologist, Pfahl formed Maxia in 1995, teaming up with Galderma Research, also based in San Diego, to screen a library of more than 1,600 RRM candidates supplied by Galderma. One of those identified previously had been shown effective in treating skin problems, and was found to have an application for CIN.
After that, Maxia worked with the Sidney Kimmel Cancer Center (SKCC), based in Paris, to identify the method of action, and reported those findings in the June 1997 issue of Nature Medicine.
Some retinoids are naturally produced and related to vitamin A. While they have been found to inhibit cancer cell growth, they cannot kill them. As described by Pfahl, the new retinoids preferentially bind to receptors in the nucleus of the cancer cell to trigger apoptosis, or programmed cell death, eliminating unneeded cells without inflammation. The binding effect makes the mechanism of apoptosis much more selective than the chemotherapeutic, an effect shown in preclinical in vitro studies of the RRMs.
Calling the new Phase III trials a "significant step forward" in Maxia's development of MX6, Pfahl credited its development as an example of how private companies and a basic research center such as SKCC can work together in developing new strategies for fighting cancer.
Maxia currently has a staff of 20 employees. It received initial funding from Galderma, Pfahl said, and has since received a second injection of funds from a venture capital firm. Currently, Maxia is negotiating with several pharmaceutical companies, and Pfahl predicted a collaboration with one of these companies by next year. *