Animal Studies for Pharmaceuticals
When companies like Bayer develop new medicines, animal testing is both necessary for scientific reasons and required by law. The innovative medical products that are developed through research on animals help to improve the lives of patients all over the world.
We would like to mention two outstanding examples that we believe have improved the lives of many people:
Treatment for Bone Metastases
About Metastatic Bone Disease
Bone metastases derive from tumor cells that migrate from the original primary tumor and invade the bone. Here, they form satellite tumors causing severe pain and often morbidity1. Bones are the third most common target organ of metastasis2. Especially tumor cells deriving from prostate and breast cancer are able to form bone metastases3.
Prostate cancer is the second most common cancer in men worldwide, responsible for over 250,0004 deaths in 2010. Castration resistant prostate cancer (CRPC) is characterized by tumor growth that resumes despite hormone therapy. More than 84% of men who develop CRPC will also experience bone metastasis.
Breast cancer is the most common cancer in women worldwide, with nearly 1.7 million new cases diagnosed in 2012. Although the number of deaths related to breast cancer has declined over the last years, metastatic cases are still universally incurable5. In about 5% of women metastases are already found at the time point of diagnosis, of which 70% harbor bone metastases6.
What role did animal studies play?
Bayer's alpha-particle releasing radioactive drug was approved in 2013 for the treatment of CRPC patients suffering from bone metastases. To test whether this drug can also be used to treat bone metastases derived from breast tumors, Bayer researchers and their partners used rodents - primarily mice - to test the drug's tumor-fighting effects in a metastatic breast tumor model, as is common in cancer research.
In each study, there was a control group of animals that were not treated with the drug and test groups that received different doses of the drug. In the study described here, each group consisted of seven mice. This number was determined by statistical methods to ensure meaningful results.
Once the groups had been assembled, the mice were implanted with isolated tumor cells to induce the formation of bone metastases. The researchers then kept the mice under close observation for several weeks in order to monitor the progression of the disease, the tolerance of the preparation and the general well-being of the mice.
At the end of the study at a predetermined time, all the mice used in the study were euthanized. This is required by law. Samples were taken from each animal to answer questions about the effect of the drug on the tumor and the side effects on healthy organs. Clinical trials on humans only took place after it had been proven that the drug was tolerated to an acceptable degree when administered in an effective dose.
Outcome and Outlook
The animal study described here indicated that the alpha particle-emitting radioactive therapeutic agent can reach and limit the growth of breast cancer bone metastases. It also markedly improved the well-being of the treated mice as compared to untreated animals.
Treatment for Thrombosis
About thrombosis
Thrombosis is a serious and often life-threatening complication of cardiovascular disease in which blood coagulation and platelets are over-activated, forming blood clots that block circulation. Bayer's anticoagulant has been tested in the prevention and treatment of thrombotic and thromboembolic events. It is now approved in more than 130 countries for a wide range of venous and arterial thromboembolism-related indications.
What role did animal studies play?
The team of scientists who developed the anticoagulant wanted to create an antithrombotic drug that could be taken orally. However, the most effective substance could not be absorbed via the guts of experimental animals. Chemical optimization proved that it was possible to modify the substance to allow absorption from the gut. Animal models were among the tests used to optimize the substance.
During the animal study, scientists induced arterial thrombosis and venous thrombi in anesthetized mice and rats. The selection of the most appropriate animal species was based on in vitro studies comparing the clotting effects in human and animal blood. To reduce the number of animals used in the studies, researchers developed an intravital laser microscope technique that allowed them to use a blood vessel from one animal as both treatment and control. This procedure helped to reduce the number of animals needed in the studies by more than 50 percent.
Outcome and Outlook
The anticoagulant reduced the weight of both the arterial thromboses and the venous thrombi. In 2008, it was approved in the EU for the prevention of venous thromboembolism (VTE) in adult patients following elective knee or hip replacement surgery. Since then, the treatment for thrombosis has been approved for many other indications and is now being tested for other cardiovascular diseases, such as prevention of major adverse cardiac events.