Dr. Craig Erickson, a pediatric psychiatrist at the Indiana University School of Medicine, has found initial success using an alcohol-dependency drug to improve the language and social skills of patients with autism.
Now IU has licensed Erickson’s patent on the use of the drug to Indianapolis-based startup Confluence Pharmaceuticals Inc., which aims to bring the medication, called acamprosate, to market.
Confluence founders Boyd Sturdevant and Steve Johns are pitching their company to various investors, trying to raise the $1.5 million they need to move the drug into the first round of human testing.
It’s a local example of what is a growing push globally to develop drugs to treat autism. Major drugmakers like Novartis, Pfizer and Roche, as well as small outfits like Confluence and Massachusetts-based Seaside Therapeutics, are all racing to find the first drug to significantly improve the core symptoms of autism.
Indianapolis-based Eli Lilly and Co. says its scientists are working with academic institutions to understand autism, but the company has disclosed no drugs in development to treat the disease.
Winning the autism drug race would be a financial boon for IU and the Christian Sarkine Autism Treatment Center, which Erickson directs. Market research conducted by a class of MBA students at IU’s Kelley School of Business predicted sales of acamprosate could reach as high as $400 million a year in the United States and even more if launched worldwide.
“The clinic here would stand to make considerable money,” said Erickson, 34, from his office on the fourth floor of Riley Hospital for Children in Indianapolis. The center funds a significant portion of the salaries of its 15-person staff through a series of short-term contracts with drug companies and federal, state and foundation grants.
According to the U.S. Centers for Disease Control and Prevention, one in every 110 children in the United States has an autism spectrum disorder, a phrase that includes related developmental disorders such as Asperger’s syndrome.
Patients with autism often have difficulty speaking and with social skills, struggling to make eye contact with others and to say things appropriate to an ongoing conversation.
The CDC estimates that 730,000 Americans under the age of 21 have an autism disorder. Even greater prevalence of the disease has been documented in areas of Japan, Sweden, the United Kingdom and Norway.
Researchers have little understanding of what causes autism, making it difficult to develop drugs to treat it. Antipsychotic drugs like Risperdal and Abilify are approved to treat aggression in autistic patients. But for improving the core symptoms of the disease, behavioral therapy and diet changes are some of the most common treatments.
Erickson’s research has focused on patients with a genetic mutation called fragile X syndrome. It is the leading known cause of autism, but accounts for only roughly 5 percent of all cases.
In the past decade, researchers found that fragile X syndrome causes a neurotransmitter in patients’ brains to be overly active. To reduce the activity of this chemical, called glutamate, researchers have tried to develop drugs that block a portion of brain neurons, called the mGluR5 receptor, where glutamate attaches itself.
In late 2008, Erickson read journal articles on alcohol treatment research, which had determined that acamprosate blocked the mGluR5 receptor. So he decided to try the drug in his patients, including those with fragile X and those without.
The results have been “remarkable,” according to Erickson. All patients showed improvement in language skills, speaking in longer sentences, more appropriate to the social setting. Eye contact improved in a couple of patients, but not in several others.
In Erickson’s case study notes, he describes a 23-year-old male, called C, who took acamprosate for 16 weeks:
“C’s language pragmatics were described as improved, marked by an increased ability to convey his needs and interests in socially appropriate ways. He was described as asking more appropriate and not just repetitive questions, and generally ‘talking more on topic.’”
The psychiatrist also has given acomprosate to patients as young as 6 years old, reporting positive effects. In only one case so far, an 11-year-old boy with autism, did the improvements wane during the course of taking acamprosate.
Erickson has tried acamprosate in only two dozen patients so far. Several large, expensive clinical trials lie ahead before it could be approved by U.S. regulators for sale.
He was confident about trying the drug in the first place because it had already proved safe for decades as a dampener of withdrawal effects in alcoholics trying to beat a drinking addiction.
But the patents on acomprosate, also known as Campral, have now expired, making it widely available in a cheap generic form. Drugstore.com lists 180 tablets of the drug for a price of $161.24.
That fact was enough to scare off the half dozen or so pharmaceutical and biotech firms who expressed an interest in licensing Erickson’s patent, according to Brad Fravel, a business development manager in the IU Research & Technology Corp., which handles IU’s patenting and licensing work.
“The commercial potential on it has always been a little bit of a double-edged sword,” Fravel said. “If you have something [for autism], it’s almost a no-brainer that there’s going to be a market for it.” But, he added, “A generic is a challenge.”
Confluence’s strategy around that problem is to reformulate acomprosate so it can be more easily absorbed by children and into more kid-friendly doses. The drug currently is poorly absorbed, meaning Erickson had to give his patients a lot of it to have an effect. Some patients developed side effects, like nausea and vomiting.
Reformulating the drug should allow Confluence to win a patent on the new drug’s “composition of matter,” a version of a patent much harder to challenge in court than the use patent Erickson currently holds.
Fravel was worried acamprosate would die after the drug companies all said no. But then Sturdevant and Johns approached IU about a licensing deal.
Sturdevant, a Bloomington resident, founded and ran Employee Counseling of Indiana, which provided mental health and “human problem-solving” services to Midwestern employers, their workers and their families. He sold the company in 2003 and has done consulting work since then.
Johns was CEO of Carmel-based eGix Inc., which sold complex telephone systems, from 1990 to 2008.
Sturdevant and Johns spent a year studying acamprosate and its potential markets before saying yes. They intend to apply for FDA approval for acamprosate as an orphan drug for a rare disease—fragile X syndrome. That could allow them to enroll fewer patients in clinical trials, saving money and time. It also makes them eligible for grants and tax incentives.
At the same time, they liked that the drug already has proved safe in humans and has a patient population eager for a treatment.
“This was a market that had an unmet need, was highly motivated and highly organized,” Johns said of autism. “Nobody tried to talk us out of it.”•