Replacing Adderall: Medicines to Change the World (Part I)

It’s a sad beginning to my series on medications set to change society and the way we live our lives. Shares in the promising biotech Alcobra Pharma plummeted 50 percent this week — and it’s disappointing news for more than just shareholders.

Alcobra, an Israeli company, is developing novel non-stimulant medications for attention deficit hyperactivity disorder, or ADHD, which affects an estimated 5 percent of children. Complicated phase III trial results for its lead drug candidate, Metadoxine (MDX), caused share prices to drop, just several weeks shy of Alcobra’s one-year IPO anniversary.

While those receiving the drug showed clinically significant improvements in their ADHD, four extreme positive placebo reactions marred the entire trial.

“So what?” you ask. Experimental drugs implode all the time, why care about this relatively small trial?

Because this drug could have been life changing. Think of the dilemma that parents across the U.S. face daily. If their child is struggling at school and has been diagnosed with ADHD, they have to debate whether or not to feed their offspring stimulants. Ritalin, Adderall, Concerta — all of these current medications carry significant side effects. It makes these people wonder: Is ADHD currently over diagnosed? Is my child a pawn in a stimulant market that was artificially created?

Parents have to reconcile all of this with their child’s situation — the likelihood they will end up in trouble, not finish high school or stray towards illegal drugs. No matter what side of the fence parents’ set up camp, there will inevitably be judgment from teachers, parents and society. I don’t pretend to know exactly what these parents battle, but Alcobra’s MDX could have advanced the equation, creating a middle ground between two very harsh realities.

That’s because the drug is an extended release, non-stimulant “GABA modulator.” It controls gamma-aminobutyric acid, a chemical that reduces nerve stimulation, rather than targeting traditional dopamine/serotonin targets that deliver a “high.” Unlike previous ADHD medications, it sidesteps the risk of recreational abuse and may improve disability for the 30-50 percent of patients unresponsive to stimulant-based treatments.

MDX also has potential applications in dementia, fragile X syndrome and various causes of cognitive fog. It’s a mighty big market, with people who can’t take for granted basic quality of life. ADHD medications could currently be aiding these off-label uses, but the extent of their abuse has made getting a prescription nearly impossible. Without the issue of black markets, MDX would be more widely available for a variety of patients to try. Conditions like cognitive impairment caused by chemotherapy medication could be lessened and controlled.

Not all hope is lost. Despite shareholder pessimism, the phase III trial did show success within the data. With only 300 participants, the issue was with the placebo arm, which was statistically skewered by four extreme responses.

Encouragingly, Alcobra’s Chief Medical Officer Dr. Jonathan Rubin promised the company would continue development of the drug: “We plan to take the complete findings of this and other MDX studies to the FDA to determine the next steps on the path to potential regulatory approval for MDX.”

If and when this drug does reach the market, the consequences will impact society just as much as they will the field of medicine. And I think we can all agree it’s about time that the treatment landscape for ADHD saw change.