Key Takeaways from Webinar: ADCs and Peripheral NeuropathyNews and Blog
On July 28, 2020, AxoSim held a webinar which explored the need for new, predictive assays to better assess ADCs’ effects on peripheral neuropathy. Rakesh Dixit, PhD, DABT, elaborated on his 30 plus years of experience in the development of antibody drug conjugates and challenges he faced during the drug development process.
For many years, scientists have been searching for effective therapeutics to control and eventually cure cancer. One of these treatments is the use of Antibody Drug Conjugates (ADCs), which were first proposed in 1967, with the first clinical trials taking place in 1975. These trials led to the first FDA approved ADC in 2000. While ADCs hold immense promise, their effects have been severely limited by side effects, including peripheral neuropathy. Rates of peripheral neuropathy in ADCs ranges from 19% to over 85%. Although there is not a complete understanding of how ADC’s large molecules impact the nervous system, Dr. Dixit mentioned “there are many things that lead to off-target toxicities.”
The majority of ADCs use tubulin inhibitors, which are known to cause peripheral neuropathy. Of the 172 Antibody Drug Conjugates using tubulin inhibitors, only 4 ADCs have been approved for use in humans, while 52 have been discontinued, and 116 are still being tested preclinically or clinically. Since the field of ADCs is rapidly growing, it is crucial we find better ways to mitigate the side effects, including peripheral neuropathy.
Historically, preclincally, peripheral neuropathy caused by ADCs has been predicted using animal testing. But, these tests are expensive, difficult to conduct, and inaccurate. Dr. Dixit added “It is possible to reduce PN with better selection of the antibody, but you also need a more accurate in-vitro assay. AxoSim’s PN assay provides a great replacement for inaccurate preclinical animal testing.”