Editor

Topping last week's news: Outcomes for ImClone Systems Inc. with its Erbitux for cancer, and Amgen Inc.'s ambivalently received results from an FDA panel meeting related to anemia products, also widely used not only in the oncology setting but also in kidney disease, where the advisory committee focused.

ImClone's brink-of-trial settlement of the patent fight with Repligen Corp. over Erbitux (cetuximab) cost $65 million in cash, but the firm got away without paying royalties on sales of the drug, which is approved for colorectal cancers and head and neck tumors.

Wall Street seemed to view Repligen as the loser in the case, and knocked more than 18 percent off the company's stock value on the news, even though Repligen stands to net about $40 million from the agreement after sharing with the Massachusetts Institute of Technology, its co-plaintiff in the case slated for trial this week.

As Elemer Piros, analyst with Rodman & Renshaw, pointed out, ImClone killed two birds with one stone in the out-of-court pact, getting not only royalty-free rights to disputed U.S. Patent No. 4,663,281, but also the same for U.S. Patent No. 5,665,578, owned by Abbott.

The pharma firm sued ImClone for patent infringement earlier this year but, under a previous agreement between Abbott and Repligen, the latter has legal rights to sublicense the patent, so ImClone was able to sidestep that skirmish.

ImClone rose somewhat on word of the Repligen news, but took off even more the next day, Tuesday, when nondetailed but promising results were disclosed from the FLEX study done by ImClone's partner, Merck KGaA.

The pivotal, 1,100-patient study found that Erbitux, when combined with chemotherapy (vinorelbine plus cisplatin) met the primary endpoint of increasing overall survival in advanced non-small-cell lung cancer, compared to chemo alone. (FLEX is an approximate acronym for "First-Line Treatment for Patients with EGFR-Expressing Advanced NSCLC.")

But Merck didn't say more. Full results are slated for an unspecified, upcoming scientific meeting, which left analysts to speculate about whether Erbitux met or beat the high bar set by Genentech Inc.'s Avastin (bevacizumab), cleared for colorectal and lung cancers. Though patients with some subtypes of NSCLC can't use the drug - and those subtypes were among patients enrolled in Merck's FLEX study - Genentech has shown overall survival with Avastin hit 12.5 months vs. 10.5 months with the control, chemo-only arm, which could be difficult for Erbitux to surpass.

Even without details, the FLEX success raised some eyebrows, since a Phase III study by U.S. partner Bristol-Myers Squibb Co. earlier this summer failed. That study, though, tried a different chemo combination, paclitaxel and carboplatin - more popular in the U.S. - and made adjustments to the protocol when the 600-patient study was half-enrolled.

In any case, analyst Brian Rye with Janney Montgomery Scott LLC said the market is more than large enough for both drugs as combo products with chemo against NSCLC. Since Avastin takes about half the market share of the entire market, or two-thirds of the nonsquamous subset that the compound targets, "ample room [remains] for Erbitux to garner meaningful sales without encroaching on Avastin," he told BioWorld Financial Watch.

Industry observers Tuesday had their sights on Amgen more than ImClone, though. That day, the Cardiovascular and Renal Drugs Advisory Committee and its Drug Safety and Risk Management Advisory Committee voted 14-5 against setting a hard-stop target of 11 g/dL for the use of erythropoietin (EPO) stimulating agents (ESAs) in dialysis and predialysis patients with chronic kidney disease, because of safety concerns.

Amgen sells the red-blood-cell boosters Epogen (epoetin alfa) and the second-generation product Aranesp (darbepoetin alfa), both approved for anemia in cancer patients and in CKD. (See BioWorld Financial Watch, Aug. 6, 2007.)

A majority of the panelists recommended that a target range of 10-12 g/dL is more appropriate, and Amgen seems to have dodged a major bullet. If the FDA falls in line with the advisory panel's view, as is customary but not guaranteed, Johnson & Johnson also would benefit. The firm makes the ESA Procrit (epoetin alfa).

Jennifer Chao, analyst with Deutsche Bank, called the panel's advice a "major relief to the $2.5 billion renal franchise," where a reduction to 11 g/dL could have cost Amgen at least $600 million.

Now, investors are waiting to hear from the Centers for Medicare & Medicaid Services. This summer, CMS restricted the use of ESAs, refusing to pay for them when a cancer patient's hemoglobin count exceeded 10, and was considering a similar policy for kidney patients.

CMS made known the oncology decision a few days after the FDA's advisory panel put forth its cancer recommendations, but nobody knows if CMS will take action shortly on ESAs in kidney disease or wait until the FDA decides on a revised label, expected in the second half of this year.

"The major disconnect has been a departure by FDA, CMS and the [cancer advisory] panel on the importance of quality of life [QOL]," Chao said.

"EPO has been used increasingly over the last decade to improve QOL - enabling patients to withstand optimal chemo, have improved daily living and certainly avoid blood transfusion," she noted.

Lately, though, the FDA and CMS have changed their ideas of treatment goals, Chao said.

"Avoiding blood transfusions was highlighted by the panel yesterday as a symptom, not the ailment," and treating with ESAs only to avoid blood transfusions was seen as "a throwback to standard of care in the 1980s and 1990s," she said.

"Re-focus on the QOL issue is essential in successfully revoking" the CMS decision in oncology and keeping the current product labels there, Chao added.

On the brighter side for Amgen, "the fact that many panelists expressed, 'There are no data to show 12 g/dL is worse than 11,' suggests a potential trend that FDA may be more data-driven - potentially tipping favor back to Amgen," though "numerous obstacles lie ahead, unrelated binary events, which are difficult to risk-mitigate," Chao pointed out.