In 2010 Pfizer (PFE) voluntarily withdrew its then-new hypertension drug, sitaxentan (Thelin) after liver toxicity claimed two lives. It was an expensive failure. The drug had already been marketed throughout Europe, Australia, and Canada. Clinical trials were halted and plans to file for FDA approvals were shelved.
Another sad scenario involved a widely used chemo drug with success at curing leukemia. Despite amazing gains in extending life, and even curing leukemic children, treatment with the widely used class of chemotherapeutic drugs, anthracycines showed to increase the likelihood of heart failure by 7.5% within 30 years. Breast cancer victims treated with the same type of drug are subject to similar side effects, but with lower risk, at 1-2%.
Currently, about 20% of all drugs fail in trial because of adverse reactions related to toxicity, according to the Tufts Center for the Study of Drug Development. A new frontier in biotech has emerged to help identify toxicity issues in the early states of drug development before expensive clinical trials are initiated. Small cap Compugen (CGEN), an Israeli-based company, partnered with global giant Merck Serono, a division of Merck KGaA (MKGAY) to serve the 'fail early' niche. The new start-up, Neviah Genomics, provides cutting edge tools to help identify the toxicity profiles of new drug candidates before they proceed to clinical trial testing.
Sometimes drugs introduced to reduce toxic side effects meet with fast approval. Last year, privately held BTG International Inc., won FDA approval for Voraxaze (glucarpidase) to help lower toxic, high blood levels stemming from treatment with methotrexate. Patients who are treated with high doses of the widely-used chemotherapy drug are at increased risk for kidney failure.
In its report, the FDA said, "Prolonged exposure to high levels of methotrexate can result in kidney and liver damage, severe mouth sores, damage to the lining of the intestine, skin rashes, and death due to low blood counts," according to Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "Voraxaze is an important new treatment option for cancer patients aimed at preventing these toxicities associated with sustained high levels of methotrexate."
While toxicity risks associated with chemotherapy are well known, dangers related to commonly prescribed imaging techniques like cardiac angiography and CT (computed tomography) scans that use contrast are still below the radar of many patients. Contrast solutions that contain iodine and barium are routinely used to enhance clarity and visualization of body structures and tissues, enabling more precise diagnosis and treatment. But it can be dangerously toxic. Patients with prior kidney damage who undergo angiographic imaging are at risk for contrast-induced nephropathy (CIN) resulting from exposure to the intravascular iodinated contrast medium.
As the frequency of diagnostic imaging and interventional studies increases, particularly among an aging population, the incidence of CIN also rises. The problem has intensified as diagnostic imaging and interventional studies are routinely prescribed and ill effects are cumulative. Patients with type 2 diabetes mellitus, who frequently require coronary ngiography and coronary intervention are at risk for CIN. This can lead to potentially deadly and costly complications, and most often leads to dialysis.
There are still no FDA-approved therapies to prevent contrast-induced nephropathy (CIN). However, microcap PLC Systems (PLCSF) has developed a novel device, the RenalGuard System that may offer protection through a therapeutic approach. The device, which limits toxin exposure in kidneys, has already achieved success in European clinical trials. Findings in two Italian studies showed RenalGuard to be superior to the current standard of care. In fact, so far, RenalGuard-protected patients were found to have nearly a 70% lower rate of CIN than the control group, according to a US Pivotal trial.
If PLC Systems continues to firm up its global strategic position by widening RenalGuard distribution and sales, it could tap into a $500 million market opportunity. Currently RenalGuard is in commercial release with the Company's distribution partners in Europe as well as in several large Latin American countries including Brazil. In all, the company has established distribution channels in 17 countries throughout Europe, as well as in Latin and South America, Australia, New Zealand, China, Japan, Israel, and the UAE.
Domestically, as baby boomers age and with the incidence of diabetes on the rise, the need for protection against CIN becomes more urgent. Yet there are still few solutions in the pipeline to compete against RenalGuard. One alternative drug is CRMD001 (unique formulation Deferiprone), which targets the prevention of Contrast-Induced Acute Kidney Injury (AKI). The drug, under development by CorMedix (CRMD) has received approved Phase III Special Protocol Assessment. Recently CorMedix filed for an extension in order to maintain its status on the New York Stock Exchange.