A gene therapy that eliminates the need for radical cystectomies (complete removal of the bladder) in a particular, aggressive form of bladder cancer is undergoing Priority Review by the U.S. Food and Drug Administration.
A gene therapy that eliminates the need for radical cystectomies (complete removal of the bladder) in a particular, aggressive form of bladder cancer is undergoing Priority Review by the U.S. Food and Drug Administration (FDA). It was developed by FKD Therapies Oy with the close collaboration of the Society of Urologic Oncology Clinical Trials Consortium in a novel industry/professional society partnership.
Originally, the therapy nadofaragene firadenovec (rAd-IFN/Syn3) was developed in the lab of Colin P.N. Dinney, M.D., chairman, department of urology, division of surgery, University of Texas MD Anderson Cancer Center, Houston, and co-founder of the Society of Urologic Oncology Clinical Trials Consortium (SUO-CTC), which was critical in conducting the clinical trials.
As Dinney recalled, “I developed this drug from preclinical to Phase I with Schering-Plough Corp. Then Schering was bought by Merck, which decided not to develop it.”
That was around 2009, when the financial crisis was constraining research budgets and relegating many urologists to procedures.
To ensure that urologists retained awareness of and access to research opportunities, Dinney co-founded SUO-CTC, a network of approximately 400 academic and private practice urologists and 200 clinical sites. It works as an independent partner and consultant with biopharmaceutical companies to identify patients and sites for clinical trials, review clinical trial protocols, and meet with investigators and their collaborators to improve clinical trials.
This early, active involvement enables urologists to identify additional opportunities for companies while also expanding research opportunities for its urologist members. In addition to bladder cancer trials, the SUO-CTC also collaborates in partnership with pharmaceutical and biotechnology companies to develop and conduct trials for prostate cancer and renal cancer.
“It’s a very lean organization that offers enormous advantages” to its pharma partners, Gennady Bratslavsky, M.D., told BioSpace. Its expertise encompasses many urologic sub-specialties including, but not limited to, sequencing and biomarkers, and insights from practicing physicians and academic experts. “By providing this expertise early, we become an intellectual partner, which is a unique approach.
“The development of nadofaragene firadenovec is a prime example of an effective collaboration between the SUO-CTC and pharma to develop a novel therapeutic that addresses an unmet need for patients with bladder cancer,” Bratslavsky said.
When the SUO-CTC was formed, however, it started at ground zero.
“We needed a trial to jumpstart the activity of the bladder cancer committee, and I had discussed nadofaragene firadenovec with the president of FKD Therapies Oy,” Dinney said.
Not only did Dinney discuss his Phase I data, but he also discussed a particular patient. “I had a patient with Alzheimer’s disease with high-grade non-muscle-invasive bladder cancer who had not responded to BCG therapy. His wife felt surgery was not a good solution because of his Alzheimer’s,” Dinney said. He enrolled the man into a trial, and administered one of the higher doses. “He remained disease-free until he died of Alzheimer’s four years later.”
FKD licensed the therapy and Dinney negotiated for the SUO-CTC to have exclusive control of the trial sites. The organization recruited 13 sites from among its members for Phase II trials, and quickly enrolled patients. Larger Phase III trials also were recruited quickly and with favorable results.
“This treatment is truly a game-changer and adds a powerful new intravesical therapy for patients with Bacillus Calmette-Guérin (BCG) unresponsive bladder cancer,” Dr. Michael Cookson, president of the Society of Urologic Oncology (SUO), said in a statement.
Specifically, nadofaragene firadenovec is designed for patients with high-grade non-muscle-invasive bladder cancers. The therapy is an adenovirus vector-mediated interferon alfa-2b gene therapy. It was granted Breakthrough Therapy designation by the FDA. Industry watchers say it has the potential to compete with Merck’s Keytruda®, which was approved in January for the same condition.
Approximately 81,000 people in the United States are diagnosed with bladder cancer every year, according to the American Cancer Society, making it one of the most common cancers. It also is one of the deadliest cancers, claiming nearly 18,000 lives in the U.S. this year alone.
The gene therapy is administered to patients via a catheter, directly into the bladder, once every three months. In trials, it helped the body produce high quantities of a protein that fights the cancer. In the Phase III trial, 53% of patients achieved a complete response as early as three months, and 24% at 12 months. In patients with papillary disease, 73% achieved high-grade recurrence free (HGRF) survival at three months and 44% at 12 months.
Nadofaragene firadenovec uses an adenoviral vector to deliver the gene to the cells of the bladder wall, where breaks down and releases its DNA – including the interferon gene. That gene is taken into the nucleus and transcribed, ultimately resulting into the secretion of high quantities of interferon alfa-2b proteins being released into the microenvironment of the tumor.
“Now, we’re waiting for approval from the FDA and looking at opportunities to expand indications. Discussions are ongoing,” Dinney said. The SUO-CTC also is considering trials to introduce the drug earlier in the course of the disease, as well as including it in combination therapies.” His own lab – but, as yet, not the SUO-CTC – is investigating a companion diagnostic for early applications.
FKD, for its part, led the development, manufacturing and regulatory submission efforts. Assuming the FDA approves nadofaragene firadenovec, FKD plans to license the gene therapy to FerGENE for commercialization in the U.S. and to advance global development.
