>> Two Potential Cancer Drugs Fail to Clear Hurdles at FDA
By ANNA WILDE MATHEWS Staff Reporter of THE WALL STREET JOURNAL May 4, 2004
GAITHERSBURG, Md. -- A Food and Drug Administration advisory committee voted against approving two cancer drugs after the agency raised significant questions about the evidence the companies presented to show the medicines worked in treating skin cancer and brain metastases from breast cancer.
The advisory panel voted 13 to 3 against approval of Genasense, a treatment for advanced malignant melanoma from Genta Inc., of Berkeley Heights, N.J., and French partner Aventis SA.
Voting 16-1, the panel also rejected RSR13, for breast-cancer patients whose disease has spread to their brains. RSR13 is made by Allos Therapeutics Inc. of Westminster, Colo. The FDA tends to follow the recommendations of its advisers.
Both decisions had been closely watched for signs of how flexible the FDA will be in granting approval for cancer medications, as clinical trials for both drugs ran into major setbacks. Last May the FDA cleared Iressa, a drug for non-small-cell lung cancer that helped shrink tumors in about 10% of patients in one limited study, while other studies showed no effect. The oncologic committee had voted in favor of Iressa.
Separately, the FDA posted materials for the committee's meeting today, which will focus on a high-profile issue: The safety of several bioengineered treatments for anemia, including Amgen Inc.'s Aranesp and an older drug sold by Amgen as Epogen and by Johnson & Johnson as Procrit. In particular, the panel will examine some recent trials that suggested a possible, although still controversial, link between these so-called EPO treatments and a faster progression of cancer.
Tumor Shrinkage
Genasense, combined with a chemotherapy drug, failed to extend patients' lives enough to be statistically significant in a 771-person trial, missing the main target of the study. Genta officials argued that the drug helped shrink tumors and slow the progress of the disease. But FDA officials raised significant questions, mostly focused on how the company measured results, including whether the timing of checks of patients' tumors might have skewed the findings.
In the end, the committee decided that Genasense hadn't shown enough evidence that benefits outweighed potential risks to patients. Genta's chief executive, Raymond P. Warrell Jr., said the company was "very disappointed, but we continue to think we have very good data." Genta is also testing Genasense for several other types of cancer.
Genta shares, which fell more than 40% Friday on the heels of an FDA briefing, plummeted another $3.49, or 41%, to $5.11 at 4 p.m. EDT yesterday on the Nasdaq Stock Market. The shares hit an intraday low of $4.50, below the previous 52-week low of $7.20 set last May.
For RSR13, which is supposed to enhance the effectiveness of radiation for brain metastases, Allos mounted a trial aimed at showing the drug could extend cancer patients' lives. The results fell short of the statistical bar. Instead, Allos zeroed in on the study's 115 breast-cancer victims. Among them, people on the drug lived 4.1 months longer on average than those who weren't.
The FDA said the breast-cancer group was small and the result should be considered "exploratory." The committee voted overwhelmingly that the drug's study results didn't represent "substantial evidence of RSR13 efficacy" in breast cancer patients. Allos Chief Executive Michael Hart said the company was "obviously disappointed" but planned to move forward with a larger trial.
The stock of Allos, too, has fallen sharply. It sank 45% to $2.55 on Friday on the Nasdaq market when the FDA issued a negative review. Yesterday, it slipped another 6%, or 16 cents, to $2.39.
Enemia [sic] Drugs in Spotlight
Today, the committee is set to review safety data for the anemia treatments known generically as erythropoietin, or EPO, which boost the body's production of oxygen-carrying red blood cells. Drugs like Aranesp and Procrit/Epogen are generally used to combat anemia in patients with kidney disease or who are undergoing cancer chemotherapy.
The panel will delve into the question of whether there may be a link between EPO use and the pace of the spread of cancer. The three main manufacturers of EPO-style drugs -- Amgen, Johnson & Johnson and Switzerland's Roche Holding AG -- all say they believe those studies were flawed, and add that their internal reviews of safety data for their drugs has show no sign that EPO stimulates tumors to grow faster.
The FDA, however, considers the matter unsettled. In a briefing paper prepared by agency staffers and posted on its Web site yesterday, the FDA called for more large clinical trials designed to clear up the current confusion. The panel will also consider evidence linking EPO to a higher risk of blood clots.
Drug makers such as Johnson & Johnson acknowledge that the clotting problem is real, but say it emerged as a serious issue only in studies that attempted to boost blood oxygen well above normal target levels. Those studies have since been discontinued, said Adrian Thomas, Johnson & Johnson's vice president for drug safety, in an interview. <<
>> An F.D.A. Advisory Panel Rejects 2 Cancer Drugs
By ANDREW POLLACK Published: May 4, 2004
In deciding whether to approve cancer drugs, the Food and Drug Administration often has to balance the emotional demands of desperate patients against the cold, hard statistics from clinical trials.
Yesterday, the statistics won. An F.D.A. advisory panel withheld its recommendation for two drugs developed by small biotechnology companies, saying the companies had not sufficiently proved the drugs worked. The vote means that the F.D.A. is likely to reject the drugs - Genasense, developed by Genta Inc., and RSR13, developed by Allos Therapeutics.
Both were expected to be the flagship products of their companies.
Shares of Genta plunged $3.49, or 41 percent, to $5.11 yesterday. Shares of Allos were halted in the afternoon, when they were trading at $2.39, down 16 cents. The stock of both companies had already plunged about 40 percent on Friday when negative evaluations by the F.D.A. staff were made public.
The vote was also a setback for Aventis, the French drug company that is about to be acquired by Sanofi-Synthélabo. Aventis has the marketing rights to Genasense, which it acquired two years ago for $135 million up front and total payments that could reach $480 million.
The meeting of the Oncologic Drugs Advisory Committee in Gaithersburg, Md., was closely watched as a gauge of F.D.A. policy. There has been a perception that the agency, under pressure from patient groups, has become more lenient in approving cancer drugs. Often cited is last year's approval of AstraZeneca's Iressa after it shrank tumors in 10 percent of patients in a small trial. But yesterday's discussion shows there is a limit to how far the agency is willing to bend.
"Genasense was overwhelmed by the statisticians," commented Biotech Monthly, a newsletter for investors, which suggested the agency might be tightening up. That could mean "a sad outlook on the future of biotechnology."
But other analysts said that there was no new trend and that each drug had been judged on its merits.
"I think there was a false notion out there at the start that the hurdle for approval had been meaningfully lowered or completely removed," said Dr. Jay Markowitz, biotechnology analyst at T. Rowe Price. [I agree (#msg-2989501).]
Both Genta, based in Berkeley Heights, N.J., and Allos, of Westminster, Colo., needed some leniency. The main clinical trials run by the companies did not meet their goals of prolonging lives. But each company argued there was still evidence of effectiveness.
Genta argued that Genasense, tested with a chemotherapy drug against melanoma, a skin cancer, delayed the median time before disease worsened to 74 days from 49 days for patients getting the chemotherapy alone.
Several patients, urging approval, told the committee they would not be alive were it not for the drug. One doctor told of a patient who had gone from a wheelchair to dancing at her son's wedding.
Even a congressman, Peter Deutsch, testified for approval. "By what right can government deny cancer patients a chance to save their lives," said Mr. Deutsch, a Florida Democrat, adding that he and his children were at risk for melanoma.
But the F.D.A. reviewers argued that the evidence was not convincing because of measurement problems. The committee, many of whose members are doctors, was a bit more sympathetic to the drug but still voted 13 to 3 that the evidence of effectiveness did not outweigh the risks from side effects.
Dr. Raymond P. Warrell Jr., chief executive of Genta, said in a statement that the company strongly believed in Genasense and was "committed to its ongoing development." He said the company would work with the F.D.A. to determine the next steps. Genta is also testing Genasense as a treatment for multiple myeloma and for a form of leukemia.
The vote yesterday is another setback for so-called antisense technology, a method of turning off genes that is used by Genasense.
The vote on the drug from Allos was more lopsided, with 16 members saying the company had not demonstrated effectiveness and only one saying it had.
RSR13 is designed to make radiation therapy more effective. The company tested the drug in patients receiving radiation for tumors that had spread to the brain from elsewhere in the body.
The drug did not improve survival over all, but Allos argued that the drug had doubled median survival in those whose brain tumors had originated in the breast, as opposed to other organs.
But the F.D.A. reviewers argued the finding could be spurious because the company had not defined this subset of patients in advance. If data are sliced and diced enough, they said, it is always possible to find some subset of patients appearing to benefit.
Allos has already started a trial just of patients whose brain tumors started in the breast. <<
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