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WSJ on GNTA, ALTH panel meetings:

http://online.wsj.com/article/0,,SB108362563863200846,00.html?mod=yahoo_hs&ru=yahoo

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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.
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