Pancreatic Cancer Treatment Granted Orphan Drug Designation by FDA

The FDA has granted orphan drug designation to Rexahn Pharmaceuticals’ investigational pancreatic cancer treatment, RX-3117.

During preclinical studies, the next generation, cancer-specific nucleoside analog was found to maintain anti-tumor activity in human cancer cell lines that are resistant to the pancreatic cancer chemotherapy drug, gemcitabine. Up to 40% of pancreatic cancer patients treated with gemcitabine become resistant to the drug after 30 days.

Now, patients are being enrolled into a Phase Ib clinical trial on RX-3117 that is expected to be completed in the first quarter of 2015

"Receiving Orphan Drug Designation for RX-3117 in the treatment of pancreatic cancer is an important milestone for this clinical development program," said Rexahn CEO Peter D. Suzdak, PhD, in a press release. "RX-3117 has shown to be effective in treating cancer cells that have become gemcitabine-resistant. If the results of our Phase Ib trial and future trials show similar results in gemcitabine-resistant patients, this would represent a major breakthrough in the treatment of pancreatic cancer patients."

RX-3117 acts as a novel small molecule anti-metabolite that is incorporated into cells to inhibit the synthesis of both DNA and RNA, which can cause the apoptotic death of tumor cells. The drug mediates the down regulation of DNA methyltransferase 1, an enzyme that is targeted by anticancer therapies.

In preclinical studies, RX-3117 was found to be effective in slowing the growth of several human cancer xenograft models, including colon, lung, renal, and pancreatic cancer. Additionally, the treatment was found to overcome chemotherapeutic drug resistance.

The drug also demonstrated a broad spectrum of anti-tumor activity in 50 different human cancer cell lines and was effective in 12 different mouse xenograft models, thus showing superior to gemcitabine. RX-3117 was found to retain full anti-tumor activity in human cancer cell lines that previously became resistant to gemcitabine’s anti-tumor effects.

In an exploratory Phase I clinical trial during which investigators examined the oral bioavailability, safety, and tolerability of the drug, RX-3117 exhibited an oral bioavailability of 56% and a plasma half-life of 14 hours. The drug was also found to be safe and well tolerated through the tested dose range in all patients.

The ongoing Phase Ib multi-center dose-escalation study seeks to evaluate the safety, tolerability, dose-limiting toxicities, and maximal tolerated dose of the treatment in patients with solid tumors.

The secondary endpoints of the trial include characterizing the pharmacokinetic profile of RX-3117 and evaluating its preliminary anti-tumor effects.