Eli Lilly once made a fortune on a schizophrenia drug that helped a lot of people, but came with a nasty side effect—weight gain. Now Dublin, Ireland- and Waltham, MA-based Alkermes is wagering that it can get the benefits of the original treatment without causing patients to add so many extra pounds.
Alkermes (NASDAQ: ALKS) is announcing to shareholders today that it has a new combo-drug strategy to improve upon Eli Lilly’s olanzapine (Zyprexa). This idea, to combine olanzapine with Alkermes’ proprietary compound ALKS33, is actually way beyond the “we’ve got an idea” stage. Based on encouraging results from a short-term study of 106 healthy volunteers, Alkermes says it is getting ready to take this compound into the second of three stages of clinical trials normally required for FDA approval.
There’s a big potential market here if Alkermes can convince doctors and payers that it has something better than a cheap generic. Eli Lilly’s original olanzapine generated more than $5 billion in sales in 2010, the last full year of sales before its patent expired. The market was huge then, even after researchers began to better understand the drug’s side effect profile. One federally funded study from 2009 showed that patients who started on the drug, at an average weight of 118 pounds, ended up gaining 18.7 pounds on average after about 11 weeks on olanzapine. Despite those results, and evidence that showed olanzapine caused the biggest weight gains in its class, it continues to be widely prescribed in its generic form.
Alkermes, knowing this, designed a study in 106 healthy volunteers (who don’t have schizophrenia), and randomly assigned them to get standard olanzapine or olanzapine plus ALKS33—a combo it is now calling ALKS3831. Although the volunteers were only followed for three weeks, researchers quickly saw a difference in weight gain. Patients on the Alkermes drug combo gained an average of 2.5 kilograms (about 5.5 pounds) compared with 3.4 kilograms (7.5 pounds) in the comparison group. The result is far from iron-clad proof that the new regimen offers a real medical benefit, but it was statistically significant—meaning researchers can say with confidence the result isn’t a fluke. The results were encouraging enough for Alkermes to invest its resources in a bigger and longer-term study of schizophrenia patients that will begin in 2013.
“We’ve been hammering hard on building this CNS [central nervous system] drug pipeline, and this is one example,” says Alkermes CEO Richard Pops. “Big Pharma isn’t doing much in CNS anymore, but the unmet need there is still vast.”
In terms of this experiment, Pops says, “we’d never argue this is definitive, but it certainly explains to our shareholders why we’d go into a Phase II trial in schizophrenia patients.”
Many other pharmaceutical companies have experimented with new and improved versions of olanzapine, but none are thought to be as far along in development, Pops says. Israel-based Teva Pharmaceutical has expressed interest in the field publicly, he says.
Much work needs to be done to prove the Alkermes hypothesis. The Alkermes drug added to the mix, ALKS33, is an opioid receptor modulator that was designed to curb addictive behaviors. It has passed a mid-stage clinical trial as a treatment for alcohol dependence, but hasn’t been tested alone as treatment for weight loss. The drug’s future as a treatment for alcohol dependence is on hold for now, Pops says, until the company can agree with the FDA on mutually acceptable goals for future studies.
For now, the proprietary Alkermes drug will need to be given in combination with olanzapine in clinical trials. If the combo continues to progress, Alkermes will want to move ahead with a drug that puts both active ingredients into a single pill. “Ultimately, it will be a single tablet, but we’ll have talk to FDA about it,” Pops says.
Alkermes made the announcement just a couple of days before jetting off to the JP Morgan Healthcare Conference in San Francisco, the biotech industry’s biggest annual event for investing and dealmaking. The company is also announcing today it has gotten a patent that lasts until 2030 on its once-monthly injectable form of aripiprazole lauroxil. That drug for central nervous system disorders, including schizophrenia, is designed to come as a once-monthly injection that it hopes will improve upon Bristol-Myers Squibb’s blockbuster treatment aripiprazole (Abilify). Alkermes is also planning to release clinical data in the first half of 2013 on ALKS5461, a combo drug for treatment-resistant depression that is also based partly on ALKS33.
The overarching story this year at Alkermes will be more about the R&D pipeline for central nervous system disorders, and less about the big merger with Elan Drug Technologies, first announced in May 2011. Essentially, that’s old news. And while people were rightly paying attention to how that merger would change the complexion of Alkermes, they might not have noticed some of the drugs that were progressing in the pipeline. “Our CNS pipeline is getting more exciting,” Pops says.