Individuals with complete spinal cord injuries face a lifetime of complications, not the least of which is fecal incontinence. But those patients – approximately 250,000 in the U.S. who live with the condition, four out of five of them men – represent just the tip of the iceberg for those with rectal diseases, including anal fissures and fistulas.

Nearly 8 percent of non-institutionalized adults in the U.S., or some 20 million individuals, suffer from fecal incontinence, or loss of bowel control. The condition, which results from damaged or weakened anal sphincter muscles, can occur at any age and often leads to placement in a long-term care facility because family members cannot adequately manage their loved one's condition at home.

Unlike the need, treatment options are sparse. No prescription drugs are approved in the U.S. for the condition.

RDD Pharma Inc., of Tel Aviv, saw that imbalance as a niche opportunity.

Founded in 2008 in a life sciences incubator in Israel's Office of the Chief Scientist, RDD is focused on fast track development and commercialization of therapeutics for anorectal diseases and gastrointestinal disorders, using the 505(b)(2) pathway. Based on its early progress, in 2012 the company attracted outside funding from its main backer, Orbimed Advisors, and smaller stakes from Israeli seed investor Ofakim Hi-Tech Ventures and the German investment fund Corporate Finance Holding GmbH.

The company's lead candidate, RDD-1219 (nifedipine), is a calcium channel blocker formulated as a "capository" – a combination suppository and capsule – to treat pain associated with anal fissure. RDD-1219 is expected to start a phase III study in Europe in the first quarter, followed by a second phase III in the U.S. that also expects to begin enrolling patients this year. The drug is designed to normalize internal anal sphincter pressure, leading to a healthier blood supply to stimulate healing of the area. In two phase II studies that enrolled 54 patients in total, RDD-1219 demonstrated superior pain relief to Rectogesic, a glyceryl trinitrate ointment approved in the U.K., without that product's side effect profile, which includes headaches in a majority of users.

RDD – an acronym for rectal drug delivery – also is preparing to advance RDD-0315 (phenylephrine), an alpha agonist also formulated as a capository, into a phase IIb study this year in fecal incontinence. The company reported in January that a pilot study of the compound, which sends a signal to the anal sphincter to contract, met its efficacy endpoint. The double-blind, crossover phase IIa study, conducted in 19 patients with spinal cord injury, showed a statistically significant 25 percent reduction in the number of fecal incontinence episodes at eight and 12 hours following administration in the treatment arm compared to placebo.

RDD-0315 also was well tolerated by patients and met safety goals. No systemic absorption was observed, with plasma levels of RDD-0315 below detectable limits.

'DON'T NEED A LARGE COMMERCIAL ORGANIZATION'

Jason Laufer joined RDD two years ago as CEO, attracted by the urgent need to treat a sensitive medical condition that was receiving almost no attention from the pharma world.

"Although many companies are in the gastrointestinal space, no single company is focused on the last stop of the gastrointestinal tract, which is the anal-rectal region," Laufer told BioWorld Today. "That's for a variety of reasons, not the least of which is that people who suffer from anal-rectal diseases don't talk about them."

Without discounting the seriousness of rotator cuff surgery, stent placements and chemotherapy treatments – common topics of public conversation – Laufer maintained that anorectal disorders such as anal fissure and fecal incontinence are "highly" prevalent and debilitating.

"This was an opportunity to be a sort of pioneer," said Laufer, who started his career nearly three decades ago in clinical and regulatory affairs at New York-based Pfizer Inc. and subsequently held executive roles in specialty pharma and medtech.

The potential market opportunity isn't exactly trivial, either. The U.S. market for anal fissure treatment is estimated at $600 million, with the fecal incontinence market projected to be approximately $3 billion.

The company's capository formulation is designed to provide the exact amount of drug directly to the affected area with maximum patient compliance. Regulators have guided the company that the drug/device combo will be regulated as a drug, but the complete package is key to a user-friendly solution.

"Without the delivery system, patients will not consistently administer the drug," Laufer said. "It's an innovative way to treat a disease that occurs in a very problematic place."

And that's not just the unpleasantness factor. The anorectal region has unique physiological challenges, including high temperature and humidity, frequent abrasion and absorptive capacities, he pointed out.

RDD's candidates also are formulated for extended release, typically giving patients four to five hours of freedom to perform a variety of common activities, including work, shopping, medical appointments and social engagements, according to Laufer.

If the RDD-1219 phase III program succeeds in anal fissure, RDD could file its marketing authorization application in the EU next year, followed by a new drug application to the FDA in 2018. EU authorities indicated they will accept a single phase III study that enrolls 300 patients, while the FDA is looking for data on 500 patients, Laufer said, so the company will enroll another 200 in the second phase III.

RDD holds patents on two additional indications – pruritus ani, or chronic anal itching, and cancer treatment-related radiation colitis – that extend its "innovation bin," Laufer added. And the company has kept its overhead to a minimum, with the equivalent of just four full-time equivalents.

With major milestones looming, RDD is in the process of raising a $15 million series B round that Orbimed already agreed to support. The funds will allow the company to move RDD-1219 to registration in anal fissure in the EU and U.S. and to complete the RDD-0315 phase IIb program in fecal incontinence. At the point of commercialization, the company expects to have multiple options.

"The nice thing about both indications is that you don't need a large commercial organization to properly detail it," Laufer said, suggesting the company could hire its own sales team. "But we also believe the appetite by established companies for products such as these, which address unmet medical needs, will lead specialty pharmas and other commercial partners to knock on our door."