Setting the bar high usually brings about one of two results: an exalting triumph or falling flat.
The result of Biomira Inc. and partner Merck KGaA ratcheting up the bar for Theratope in the interim analysis of their Phase III trial in metastatic breast cancer was not an exalting triumph, but that doesn't mean the product has completely fallen, either.
A Data Safety Monitoring Board (DSMB) conducted an interim analysis of the companies' 1,030-patient Phase III trial of Theratope vaccine and recommended the trial continue to its conclusion, expected in the second half of next year. Also, the DSMB said it had no safety concerns with current programs and wouldn't have any for Theratope trials initiated using the same development plan. That's the upside.
The bad news is that the board reviewed data that did not meet the predetermined statistical significance required for either endpoint - survival and time to disease progression. But that might be because Biomira, of Edmonton, Alberta, was going for it all, said its president and CEO, Alex McPherson.
"We designed the trial with a formal interim analysis to see if we could see rigorous data earlier than planned," McPherson said in a conference call. "We set rigorous hurdles for ourselves."
Biomira and Merck set the "p" value for both endpoints at the interim analysis at 0.0145, more difficult to reach than the standard 0.05 value normally used to demonstrate statistical significance. Had the data reached that statistically significant figure, the plan was go to the FDA with a strong filing package and discuss registration. But while that didn't happened, it merely means Biomira will continue the trial and wait for the final analysis, which will focus on survival alone.
"While we didn't meet the endpoint of time to disease progression, and this was the final review for this endpoint, we are talking about survival and clinical benefit for this trial," McPherson said. "This is a survival study and that is what is most important."
The final survival analysis will have a less-stringent "p" value of 0.03, and while McPherson expressed disappointment at not achieving the goals of the interim analysis, he said the chances of Theratope being successful are "very real, in our opinion."
But with the data still blinded to Biomira, Merck and the public, and with no way of knowing how much the endpoints missed by, The Street didn't view the news favorably. Biomira's stock (NASDAQ:BIOM) dropped 95 cents Thursday, or 41.3 percent, to close at $1.35.
Theratope vaccine contains a synthetic form of a cancer-associated carbohydrate antigen, Sialyl Tn. The vaccine is intended to stimulate a patient's immune system to control cancer. In the call, McPherson pointed to the board's recommendation of completing the trial and it saying it had no issues with the initiation of similar trials as a sign that perhaps the trial was going well. The board is required to stop trials that do not help patients.
"If there is any indication that patients are not getting any clinical benefit or are being disadvantaged, [the board] would have to stop the trial," he said. "[The board] recommended the trial go to final analysis. Although that isn't saying to us that there is a high probability of this being successful, we do have some indication of clinical benefit for patients, or at least not disadvantaging them."
And since the DSMB said further trials using the same development plan would be fine, Biomira and Darmstadt, Germany-based Merck said they enrolled the first patient in a Phase II trial of Theratope vaccine in women with metastatic breast cancer who are being treated with aromatase inhibitors or Faslodex (fulvestrant). The study is expected to enroll about 95 patients at about 12 U.S. sites. For Biomira and Merck, it's still full speed ahead.
Last November, Biomira let go 22 employees and cut an autologous vaccine program that was in Phase I, as well as liposomal interleukin-2, which was in Phase II work. That left just the Theratope vaccine program and the BLP25 liposomal vaccine, which also is being developed with Merck. BLP25 is being evaluated in a Phase IIb study for non-small-cell lung cancer and a Phase II trial in prostate cancer patients. (See BioWorld Today, Nov. 30, 2001.)
Biomira signed with Merck to collaborate on Theratope and BLP25 in May 2001, and could receive as much as $150 million through the deal if all milestones are met. Merck would co-promote Theratope, if and when approved, in the U.S. through its affiliate, EMD Pharmaceuticals Inc. Merck has exclusive rights to Theratope outside North America, except for Israel and the Palestinian Autonomy Area. (See BioWorld Today, May 4, 2001.)
As of June 30, Biomira had C$60.1 million (US$38.2 million) in cash and short-term investments. It posted a net loss of C$7.8 million for the second quarter and C$15.4 million for the first six months of the year. In May, the company filed a $150 million shelf registration with the SEC, which it has not yet touched.