Despite a promising start, Bayer’s most recent attempt at a new targeted treatment for mesothelioma has failed early stage testing. In July, the company announced that clinical trials for the much-anticipated drug Anetumab Ravtansine did not meet expectations. This is a blow to both scientists and mesothelioma patients who had hopes of finding a new treatment method for this deadly cancer.
Traditional Treatment Options for Mesothelioma
Malignant pleural mesothelioma – a cancer of the lung’s protective lining or pleura – is very difficult to treat. It progresses incredibly quickly, and victims of the disease generally receive an average life expectancy of one year following diagnosis. The rare and aggressive cancer, which is usually caused by asbestos exposure, has a latency period of 20 to 50 years. Rapid deterioration is a hallmark trait of this disease. It leaves victims with little time to prepare, decide on treatment options, and come to terms with the nature of the debilitating illness.
Traditional mesothelioma treatment options include surgery, chemotherapy, and radiation. And while these options may extend the lives of victims, mesothelioma has no cure.
Surgery is typically a difficult, painful, and invasive process. Frequently mesothelioma patients choose to undergo surgery more for its palliative (rather than curative) purposes. Radiation and chemotherapy are both treatments that can help destroy cancer cells, but they can also destroy healthy cells in the process.
Chemotherapy has become the generally accepted first-line therapy for patients with malignant mesothelioma, however, there is no universal standard of care when it comes to second-line treatment of the disease. While chemotherapy can extend a patient’s life, reduce the size of tumors, and decrease the risk that the cancer will spread (or metastasize), in most patients the cancer still continues to progress.
Experts say the lack of options at this point in a patient’s battle with mesothelioma shows a serious unmet need for more medical research and alternative treatments. Bayer was trying to fill that gap with its work on antibody-drug conjugates (ADCs) and latest rounds of testing.
Antibody-Drug Conjugates and How Anetumab Ravtansine Was Supposed to Work
Bayer’s new biopharmaceutical advancement, Anetumab Ravtansine, is an antibody-drug conjugate (or ADC), a class of potent drug hybrids designed to specifically attack cancer cells. These types of treatment combine antibodies with cancer-killing drugs to create a targeted therapy that can distinguish between healthy and diseased tissue in the human body. ADCs are an emerging class of new cancer treatments created using advanced medical technology, yet to date only four of them have ever received market approval. Despite the massive potential that these antibody-based drugs hold, only two ADCs – one used to treat breast cancer and one for lymphoma – are available internationally today.
Researchers built Anetumab Ravtansine to target mesothelin, a marker for the protein that is overexpressed in mesothelioma cancer cells. The ADC would bind to that mesothelin and the tumor cells would take it in. The ADC’s enzymes would then release a tubulin inhibitor which would begin cell cycle arrest and apoptosis (the controlled death of cells) within the cancerous tumor. Through this process, scientists hoped that the ADC would target and kill the mesothelioma cells rather than the patient’s healthy cells, aiding in the fight against cancer.
Bayer’s Clinical Trials of Anetumb Ravtansine
The results of Bayer’s Phase I testing of Anetumb Ravtansine on 16 patients were promising when presented in 2015. Out of the 10 patients who received the drug during trials, 5 experienced tumor shrinkage and 4 remained stable. The ADC also proved safe at the maximum dose, with three of the patients continuing to receive the drug over two years after starting the trials.
This is why the next round of testing was so pivotal.
During the much-anticipated Phase II trials, researchers tested Anetumb Ravtansine on 248 patients with advanced or metastatic malignant pleural mesothelioma. All of these participants had previously undergone chemotherapy as a first-line treatment for the cancer and continued to experience tumor growth. In a randomized study, each of the patients was given either a dose of Anetumab Ravtansine once every three weeks or a weekly dose of Vinorelbine, a standard chemotherapy drug. The participants continued with these treatments until their cancer progressed or they withdrew from the study.
The study’s primary endpoint – or the main focus of the study and measure of its success – was the “progression-free survival” of the patients. This is the length of time after treatment that a patient lives with the disease but it does not get worse. Scientists measured secondary endpoints as well, like overall survival, efficacy, patient-reported outcomes, and tumor response rate.
Results of Phase II Trials
Unfortunately, the drug did not delay the progression of mesothelioma.
Bayer has not released exact numbers or complete results of the study, but it announced that Anetumab Ravtansine did not meet the study’s primary endpoint. It failed to improve progression-free survival in mesothelioma patients.
Head officers for Bayer and MorphoSys, one of the company’s partners in developing the treatment, made the following statements:
“The outcome of this Phase II study with Anetumab Ravtansine in recurrent malignant pleural mesothelioma is disappointing, in particular for the patients suffering from this serious and extremely difficult to treat disease,” stated Dr. Markus Enzelberger, Interim Chief Scientific Officer of MorphoSys.
“[W]e had hoped for a better outcome for patients,” said Robert LaCaze, Executive Vice President and Head of the Oncology Strategic Business Unit at Bayer. “We would like to thank the patients and their caregivers, as well as the study investigators for their participation and contributions in this study. Based on the available data, we remain committed to further evaluating the utility and safety of Anetumab Ravtansine across multiple tumor types with significant unmet medical need.”
Other Possible Uses for Anetumab Ravtansine
Data from these Phase II patients was enough to end testing of this much-talked-about ADC as a monotherapy for malignant mesothelioma.
Yet while these particular cancer patients may not benefit from this antibody-drug conjugate, Bayer will continue to investigate whether Anetumab Ravtansine is a viable treatment for other cancers. They are currently testing the drug against six different types of advanced solid tumors and chemotherapy-resistant ovarian cancer.
