Many patients being treated for various cancers develop anemia. Aranesp is approved by the FDA for the treatment of patients with anemia, which is caused by chemotherapy treatment of their malignant disease, rather than the underlying malignant disease itself. Essentially, it is a toxic drug which attempts to overcome some of the damage caused by other far more toxic drugs.
Amgen, the maker of Aranesp, conducted a large, multicenter, randomized, placebo-controlled study that showed Aranesp was ineffective in reducing red blood cell transfusions or fatigue in patients with cancer who have anemia that is not due to concurrent chemotherapy. The study also showed higher mortality in patients receiving Aranesp.
A letter to health professionals from Dr Sean Harper, Amgen’s Senior Vice President for Global Development, provides more details. Here is the substance of the letter:
Amgen wishes to inform you of the results of a study showing that Aranesp was ineffective in reducing RBC transfusions in patients with cancer who have anemia that is not due to concurrent chemotherapy. In addition, this study showed higher mortality in patients receiving Aranesp. In the study, Aranesp® (darbepoetin alfa) was compared to placebo in patients with active malignant disease not receiving or expected to receive chemotherapy or radiation therapy. This study was designed to establish the effectiveness of Aranesp in this new indication and failed to meet its primary endpoint of reducing RBC transfusions in the Aranesp treatment group. This study was not optimal in design to establish the effect on survival, a safety endpoint, however more deaths occurred in the Aranesp treatment group when compared to the placebo group.
Aranesp is not approved for use in this population. Aranesp is approved for the treatment of patients with anemia, which is caused by chemotherapy treatment of their malignant disease, rather than the underlying malignant disease itself. Aranesp should be used only in accordance with its approved product labeling for the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitantly administered chemotherapy.
Study Description. This Amgen-sponsored study was a Phase 3, double-blind, randomized, placebo controlled clinical study, monitored by an independent Data Safety Monitoring Board. The treatment period was 16 weeks; additional information on safety and effectiveness will be obtained from a 16 week extension study in which randomized treatment with Aranesp or placebo was continued. All patients have completed this extension study. Survival follow up will continue on patients for a minimum of 2 years. The target hemoglobin in the Aranesp treatment group was 12 g/dl. A total of 989 patients with hemoglobin (Hgb) < 11 g/dl, with active cancer, and who were not receiving myelosuppressive chemotherapy or radiotherapy were enrolled. Approximately 60% of patients enrolled had advanced (stage IV) disease.
The final analysis of the initial 16-week treatment period did not show a statistically significant effect on the primary efficacy endpoint (Hazard ratio 0.89; 95% Confidence Interval: 0.65, 1.22), with an incidence of RBC transfusions of 24% in the placebo vs. 18% in the Aranesp group, p=0.15.
In the 16-week treatment phase of the study, more deaths were reported in the Aranesp treatment group (26% (136/515)) than the placebo group (20% (94/470)). With median survival follow-up of 4.3 months the absolute number of deaths was greater in the Aranesp treatment group (216/470=46% and 250/515=49% for the placebo and the Aranesp arms, respectively, Hazard Ratio 1.25; 95% Confidence Interval: 1.04, 1.51). Follow-up of surviving patients continues. Details of this study will be presented and published in a peer-reviewed setting as soon as possible.
It is understandable that such drugs are developed and used. It is unfortunate that the commercial goal of increased profit drives drug companies to repeatedly explore additional markets for their drugs which involves vulnerable people being "used" as commercial cum clinical guinea pigs. At least Amgen has been quick to conclude this foray was a failure and they appear to be providing a reasonably transparent window on how they explored this new potential market-expanding application.
