Chemistry professor’s cancer drug clears final hurdle: FDA approval

The FDA just approved cedazuridine, the cancer drug Chemistry professor Dana Ferraris invented more than a decade ago when he worked in the biotech industry as a medicinal chemist.

For Ferraris, it’s an Oscar, Pulitzer and maybe even Nobel all rolled into one.

“If you go into industry as a medicinal chemist, you just want one – just one drug that makes it through the long journey from lab to preclinical trials to clinical trials and into someone’s pill bottle,” says Ferraris, who mentors McDaniel students in drug discovery research. “Only 1 in 5,000 compounds made in the lab makes it to clinical trials and then only about 8 percent of those make it through the trials.”

Inqovi, the trade name of the combination of cedazuridine and decitabine in pill form, “represents an important advance in treatment options for patients with myelodysplastic syndromes (MDS)), a type of blood cancer, who previously needed to visit a health care facility to receive intravenous therapy,” the FDA said in the agency’s July 7 approval announcement. The FDA also noted that in these times of global pandemic, treatments cancer patients can take in the safety of their own home are particularly important.

With Inqovi, it’s the decitabine that destroys the cancer cell and the cedazuridine that gives decitabine a fighting chance to work. Cedazuridine targets and inhibits the enzyme cytidine deaminase (CDA) which otherwise would chew up or metabolize the decitabine before it can knock out the cancer cell. 

"You want to help people – that’s why you go into drug discovery. So it’s exciting to know that there’s another weapon out there to help people with these cancers." - Chemistry professor Dana Ferraris  

“It’s all kind of surreal to think that we did it,” says Ferraris, who developed the drug while working in biotech and also conducted drug discovery research at Hopkins before joining McDaniel’s faculty in 2015. “You want to help people – that’s why you go into drug discovery. So it’s exciting to know that there’s another weapon out there to help people with these cancers.” 

Drug discovery sounds simple. Scientists pick a target – and then make a molecule that interacts with the target and ultimately knocks it out. But chemists typically make hundreds, even thousands, of compounds trying to produce one that works.  With cedazuridine, this early phase or discovery phase went quickly, taking only a year or so and only 30 experimental molecules for Ferraris and his group to synthesize a new unique molecule, never before created, that took aim at an oral treatment for MDS.

“But making a molecule that hits the target is only the beginning – now it moves into pre-clinical trials using animal models to make sure it isn’t toxic and to determine if it is orally bioavailable so it can be given as a pill,” says Ferraris, who holds McDaniel’s John Desmond Kopp Professorship in the Sciences and is chair of the department.  

If it’s safe and can be taken in pill form, the compound moves on into clinical trials with humans, which can take eight to 10 years to complete. Phase I tests safety and tolerability in healthy humans, phase II involves a small group of patients with the disease in a double-blind study, in which neither patients nor experimenters know who is receiving the drug and who is receiving a placebo, and phase III is involves thousands of patients with the disease in a several-years-long trial.

Estimates put the cost from concept to FDA-approved drug at $2.6 billion, Ferraris says. This is why biotech firms sell promising drugs to pharmaceutical company sponsors with the resources and potential profits to see the drug through the costly trials.

“I’ve had a couple of other drugs that made it into clinical trials but none of them made it past phase I,” says Ferraris. “But ok, that’s kind of normal odds. You hear about the failures but don’t hear about the successes.

“Then last June Phase III was done, it went into FDA review and on July 7 – a homerun and a big bottle of champagne!”