Drug development is much harder than it used to be. For the cancer community, rising costs and prolonged research timelines remain a growing challenge. For the brain cancer community, the barriers are even steeper.
Today, the majority of new drugs come from the pharmaceutical and biotech industry, who are better equipped to handle the nearly U.S. $ 2 billion price tag associated with taking a new concept from bench to bedside. Universities and academic medical centers have been priced out of the market. However, these companies find themselves balancing responsibilities to shareholders and investors with the public need. Unfortunately, but perhaps not surprisingly, everyone?s priorities do not always align.
Considering that new drug development can require up to 20 years from discovery to approval by the U.S. Food and Drug Administration (FDA), at a cost of U.S. $ 800 million to U.S. $ 1.8 billion, difficult choices must be made. And despite these staggering investments in time and money, a new drug still has less than an 8% chance of making it to market, down from 14% in 1985.
For patients facing an uncommon disease, such as a malignant brain tumor, these realities equate to a drought in new drug development. Since 1982, only 5 new drugs have been approved for brain cancer patients. In comparison, for lung cancer patients, this number is in excess of 50. As a neurosurgeon at the Barrow Neurological Institute and clinical trialist at the Ivy Brain Tumor Center, these are some of the harrowing statistics that my colleagues and I grapple with every day. Our Center focuses on patients with advanced brain tumors, including glioblastoma ? the cancer that recently took the life of Senator John McCain.
For our patients, market forces and the complexity of their disease have left them on the bottom rung of the world?s drug development priorities. In spite of this, our biological understanding of malignant brain tumors has never been more comprehensive, thanks in large part to our medical and scientific communities.
Accelerated Phase 0/2 Clinical Trials
Despite the odds, the answers are out there, waiting for breakthroughs like we have seen with immunotherapy for cancers like melanoma and drug cocktails for viruses like HIV. Federal funding for brain tumor research remains low, but decades of discouraging results have emboldened scientists and clinical investigators to think out of the box. At the Ivy Brain Tumor Center, innovation has arrived in the form of Phase 0 clinical trials, specialized studies that match patient genetics with drugs that have never been trialed in brain tumor patients, offering a rare glimpse of the how their individual tumors respond to drugs in days, not months or years.
Phase 0 trials begin with the patient receiving a small dose of an experimental drug cocktail hours before a planned brain tumor operation. During surgery, tumor tissue is collected and specialized laboratories determine if the drug cocktail reached the tumor and impacted its molecular targets.
If the answers to both questions are yes, then the patient begins daily treatment days within days of surgery. Alternatively, if the experimental drugs do not work, that is valuable information, too, as is the time and effort saved by not enrolling patients onto a futile therapy. The funding and time needed for our current system of brain tumor drug development is ill-suited for today?s brain tumor patients.
Our approach, enabled by a U.S. $ 50 million grant from the Ben & Catherine Ivy Foundation, the largest such commitment in brain tumor research history, aims to level the playing field for patients who are in the fight of their lives. Over 138,000 Americans are living with a malignant brain tumor and 9 out of 10 diagnosed with glioblastoma die within five years.
In combining rapid Phase 0 studies with new classes of agents, patients today can know whether new regimens are relevant to their individual tumor, not just to cell cultures and laboratory animals.
 Sanai N, Li J, Boerner J, Stark K, Wu J, Kim S, Derogatis A, Mehta S, Dhruv HD, Heilbrun LK, Berens ME, LoRusso PM. Phase 0 Trial of AZD1775 in First-Recurrence Glioblastoma Patients. Clin Cancer Res. 2018 Aug 15;24(16):3820-3828. doi: 10.1158/1078-0432.CCR-17-3348. Epub 2018 May 24. [PubMed][Article]
 Bao X, Wu J, Sanai N, Li J. Determination of total and unbound ribociclib in human plasma and brain tumor tissues using liquid chromatography coupled with tandem mass spectrometry. J Pharm Biomed Anal. 2019 Mar 20;166:197-204. doi: 10.1016/j.jpba.2019.01.017. Epub 2019 Jan 11. [PubMed][Article]
Last Editorial Review: April 12, 2019
Featured Image: Nader Sanai, MD, FAANS, FACS Courtesy: © 2010 – 2019 Ivy Brain Tumor Center. Used with permission.