By Mary Welch
Biomira Inc. started what is expected to become the largest metastatic breast cancer trial ever, with 900 evaluable patients in the Phase III study testing Theratope, a synthetic, carbohydrate-based vaccine.
"It's a rigorous trial," said Alex McPherson, president and CEO of Edmonton, Alberta-based Biomira. "Nobody will be able to tell who has the active formulation."
The randomized, double-blinded trial will evaluate Theratope's effectiveness in treating patients with metastatic breast cancer following first-line chemotherapy. The trial will take place at 70 to 75 sites, with the endpoints being time to disease progression and survival. About 40 sites will be in the U.S., and the rest in Europe. Canadian sites may be added later.
McPherson called the study "best designed clinical trial I've been involved in. Of course, I'm biased, but I've also participated in over 100 trials, and this is the best designed to prove its point that I've ever seen."
Biomira began the trial following a bridging study with an enhanced formulation of Theratope. The company said interim data from the 23-patient bridging study show that the new version of the vaccine appears to be as safe and 100 times more potent than the original formulation. (See BioWorld Today, Sept. 9, 1998, p. 1.)
"The trial will end in December with the data accrued in January, but already — after two or three vaccinations — we have seen antibody response in over 90 percent of the patients," McPherson said. "The FDA agreed with us. There was no reason to wait until December when the results will be at least as good as the interim data."
In earlier studies, results showed significant survival benefits for patients with metastatic breast cancer. In one Phase II study, Theratope vaccine-treated patients had a median survival of 26.6 months compared with 9.2 months for the placebo group. (See BioWorld Today, Aug. 22, 1997, p. 1.)
"This is a beautiful trial for patients," McPherson said. "[Theratope] produces no toxic results, except for a localized irritation at the site of the injection. The systemic effects are minimal, which — for women coming off chemotherapy who don't like the idea of those chemotherapy agents again — is very welcomed."
Theratope includes a synthetic antigen that mimics natural STn, a cancer-associated epitope, the expression of which is associated with disease aggression. It is conjugated to a high molecular weight protein carrier, Keyhole Limpet Hemocyanin (KLH). The improved survival observed in some patients is associated with the strength of the immune response to STn.
In this study, two groups of at least 450 evaluable patients will be used. The first group will receive a single injection of Theratope four times within a nine-week period. The second group will get only KLH, four times. The injections in both groups will also carry the adjuvant Detox-B Stable Emulsion, in order to enhance the immune response. Detox-B is produced by Ribi Immunochem Research Inc., of Hamilton, Mont.
Following this regimen, all patients are eligible to receive additional injections for up to 25 weeks if they do not have disease progression after the first round of vaccinations.
BLA Possible In Two Years
The company expects enrollment to take 18 months, with the first review for possible submission of a biologics license application (BLA) to the FDA planned six months following full patient enrollment.
McPherson called Theratope a "potential watershed in the use of active specific immunotherapy in solid tumor malignancies, such as breast, lung and colon." If the vaccine is approved, Biomira's partner, Chiron Corp., of Emeryville, Calif., will market it in the U.S., Europe, Australia and Japan, while Biomira retains the rights in Canada, the Middle East, Africa, Latin American and Asia (except China).
Although full financial details of the 1997 agreement with Chiron were not released, Biomira received under the deal's terms an up-front fee of $1.4 million; development milestone payments; 45 percent of revenues up to $150 million; and 50 percent of revenues after $150 million in the U.S. and Europe.
Biomira's stock (NASDAQ:BIOMF) closed Monday at $3.406, down $1.406. *