Sometimes no news is good news.
That seems to be the case for Amgen Inc., which Thursday disclosed top-line Phase III data showing that Aranesp (darbepoetin alfa) did not raise safety concerns in previously untreated patients with extensive-stage, small-cell lung cancer receiving platinum-containing chemotherapy. Worries have arisen of late that the red blood cell booster and earlier versions of it, Epogen (epoetin alfa) and its counterpart Procrit (epoetin alfa), can increase the risk of death and confer higher chances of cardiovascular events and tumor growth.
As a result, investors generally had low expectations ahead of data from the trial, designated Study 145. Instead, they liked the neutral-to-positive findings, as Amgen shares (NASDAQ:AMGN) gained $2.31 to close at $62.32 after trading as high as $64.40. Still, the stock remains well off its high-water mark for the year, $75.85 on Jan. 22.
"I think a lot of investors felt like the 145 trial was going to show a negative outcome for Aranesp," explained Les Funtleyder, an analyst with Miller Tabak + Co. LLC in New York. "Basically, it showed no difference," he told BioWorld Today, adding that the atypical outcome is beneficial in this case because of lingering investor pessimism. "The stock went up, just on relief."
Some of the overhang on the stock is gone, for now.
Specifically, the 600-patient trial demonstrated no statistically significant difference in the risk of death, and Aranesp's overall safety profile, including thromboembolic events, was consistent with that described in its label. The overall survival hazard ratio of Aranesp compared to placebo was 0.93, with a 95 percent confidence interval (0.78 to 1.11), and investigator-determined progression-free survival of Aranesp compared to placebo produced a hazard ratio of 1.02 with a 95 percent confidence interval (0.86 to 1.21).
On a co-primary endpoint, Aranesp generated a significant change in hemoglobin concentration from baseline compared to placebo, and Aranesp-treated patients also experienced a significantly lower risk of blood transfusions.
In summation, the findings confirm "the original intention of Aranesp in the oncology setting, lowering the risk of blood transfusions in patients with chemotherapy-induced anemia, with no effect on overall survival," analyst Joel Sendek of Lazard Capital Markets LLC in New York wrote in a research note.
Such data should allay short-term concerns over sales erosion, Funtleyder said, since the results have "somewhat mitigated" safety worries. Similarly, analyst Christopher Raymond of Robert W. Baird & Co. in Chicago published a research note saying that the Study 145 news "translates into a higher likelihood that Aranesp use in oncology stabilizes."
Collectively, Aranesp and Epogen accounted for almost $4.8 billion of the company's $13.9 billion in total product sales last year. First-quarter financial results are expected Monday, which should shed light on any recent sales weaknesses, and Amgen officials have scheduled a conference call to discuss earnings and more thoroughly explain the Study 145 results.
The trial randomized patients on a one-to-one basis to receive Aranesp 300 mcg or placebo every week for the first four weeks, followed by administrations once every three weeks for the remaining 24-week treatment period.
They were treated to a target hemoglobin level of 13 g/dL, which is higher than indicated on the product's label, with dose withholding at 14 g/dL.
Certainly the Study 145 data will be discussed at next month's FDA advisory committee meeting on Aranesp, Epogen and Procrit, though Raymond said the new findings have let some of the air out of the balloon. He predicted a "largely anticlimactic" event, though Funtleyder declined to handicap the panel session.
Last month the FDA gave the three products a black box warning on their labels to point out that the safety problems usually arise when they're dosed at levels beyond those approved. Sendek noted that the safety conclusions drawn from higher doses of Aranesp in Study 145 contradict the results of several other trials that prompted the recent label change, and called the coming advisory committee meeting "the proper forum" for discussing appropriate dosing.
Amgen, of Thousand Oaks, Calif., makes all three erythropoiesis-stimulating agents (ESAs), though Procrit is sold by Johnson & Johnson, of New Brunswick, N.J.
Looking longer term, Funtleyder expressed concern about potential competition to Amgen's EPO franchise from F. Hoffmann La-Roche Ltd.'s planned entry into the ESA market, Mircera, not to mention follow-on biologics. The FDA is scheduled to act on the Basel, Switzerland-based company's product by May 15.
In addition, Funtleyder warned that Aranesp and Epogen could take sales hits because of federal government inquiries into pricing, and taking a companywide view of things to come at Amgen, Funtleyder cautioned that to date, "the results have been modest" for its pipeline products.
"That could change in a second," he hedged, "but at the time being, we're a little bit concerned about three or four years from now."