About 273,000 individuals in the United States alone suffer the effects of spinal cord injuries. One of the most common and serious side effects is also the least talked about: loss of control over the muscles involved in elimination.
In about three-quarters of people with spinal cord damage, the anal sphincter does not receive the nerve signal to contract and hold in waste. One-third of those affected have no choice but to wear adult diapers because the only currently available treatment is a surgically implanted pacemaker device that is not a cure-all.
Tel Aviv-based RDD Pharma is developing a potentially groundbreaking remedy: a molecule proven to constrict the sphincter significantly for long periods of time.
“Most people with spinal cord damage are relatively young, and apart from that, in relatively good health,” says Dr. Nir Barak, the Israeli internist who founded RDD in 2008 to fast-track development and commercialization of innovative therapeutics for anorectal and gastrointestinal disorders.
“They report that fecal incontinence affects their quality of life even more than loss of sexual functioning. It keeps them from daily contact with family and friends because it’s a problem they cannot hide. It also affects their lifespan, due to related pressure sores and recurrent infections.”
Another three to five percent of the general population suffers fecal incontinence from an unknown cause, and it is the second most common reason families choose to institutionalize a relative.
A pilot study on people with spinal cord injuries showed that the RDD treatment enabled continence for eight to 12 hours following drug administration, with no adverse side effects or changes in heart rate or blood pressure.
Successful initial studies in Israel have led to a second investigative clinical trial beginning this spring in Hungary.
An embarrassing problem
Barak tells ISRAEL21c that he founded RDD to address the problem of anal fissure, a painful tear in the lining of the lower rectum.
Prompted by a patient’s frustration with existing treatments, he discovered that anal fissures affect an estimated one in 300 Americans, including many new mothers and people with Crohn’s and other bowel diseases. The actual numbers are probably much higher than reported, because many people don’t tell their doctors they are suffering from this embarrassing problem.
Topical drugs aren’t always effective, and surgery is radical and risky, sometimes causing permanent fecal incontinence.
Barak’s research showed that the underlying malady was a too tightly constricted anal sphincter prone to spasms. He set out to provide a solution for this unmet need.
“I learned that this area of the body has a very unique physiology,” explains Barak, now chief medical officer of RDD Pharma. “The anal sphincter has a different temperature and humidity than the rest of the body, and it is not a unified tissue. It’s a transition tissue that moves gradually from skin to the epithelial lining of the gastrointestinal tract.” Each of these surfaces has different absorption capacities.
The challenge was not finding better medications, but inventing a better way to deliver them accurately. RDD is focused on “repurposing” proven, already-approved preparations that work more effectively.
“When attempting to accurately apply medication to this area, the physician and the patient need to get to very specific spots. Two centimeters up or down, and they are not effective,” says Barak.
“Up until now, people were self-administering — not a precise way of delivering a specific drug to a specific area,” says RDD Chief Executive Officer Jason Laufer.
Anal fissure medications are administered by an RDD innovation – a combination capsule-suppository, the Capository, which recently received patent approval in the US, Japan, Korea and Australia. The system can be used to deliver medications for any anorectal condition and will be available under license for use by third-party pharma companies.
“Suppositories are quickly absorbed into the bloodstream, while ointments don’t reach all the desired sites of action,” Laufer explains. “The Capository is designed to increase effectiveness, reduce the likelihood of side effects and increase patient compliance. The drug is delivered to the exact site of the fissure, an area that would not easily be accessible otherwise.”
Patients in a pilot study in Israel have received a take-home kit containing Capositories loaded with a medication to treat anal fissures.
A few years to market
Also in RDD’s development pipeline are products for pruritus ani, or severe itching; and radiation proctitis (also called acute radiation colitis), which affects some 300,000 cancer patients every year in the United States alone.
“Radiation proctitis is truly an unmet need for people being treated with radiation therapy who as a result develop inflammation and damage to the lower parts of their colon, forcing their clinicians to stop treatment until it subsides,” says Laufer. “Radiation proctitis most commonly occurs after treatment for cancers such as cervical cancer, prostate cancer and colon cancer. There is no FDA-approved product for this disorder.”
Barak’s basic approach was validated in its early stages by the tech-transfer arm of Clalit, Israel’s largest health maintenance organization. Seed money was granted by the Office of the Chief Scientist through Ofakim Hi-Tech Ventures Incubator, while later investments came from OrbiMed and Capital Point, a German financial institution.
Various molecules in development at RDD are expected to reach the market in three to six years.
For more information, see rddpharma.com.