Alkermes advances schizophrenia prodrugs in shift from drug delivery
This article was originally published in Scrip
In its quest to become known as a drug developer as well as a drug delivery partner, Alkermes will report various data points for its central nervous system (CNS) pipeline in 2013, starting with Phase II plans for ALKS 3831 and a new patent for aripiprazole lauroxil (formerly ALKS 9070), which both treat schizophrenia.
The Dublin, Ireland-based company wants to build on it history of drug formulation expertise – including the long-acting injectable technology behind Janssen's Risperdal Consta (risperidone) and the opioid modulator platform that supports Alkermes' Vivitrol (naltrexone for extended-release injectable suspension) – with new drugs for the CNS market.
"We're building a portfolio of CNS products that could be a game-changer for our company," Alkermes chairman and CEO Richard Pops told Scrip.
Pops said the company could grow from generating $500 million in annual revenue that comes largely from products developed by partners to one with revenue from wholly-owned blockbuster drugs that target schizophrenia and other CNS disorders.
Alkermes anticipates $490-$530 million in fiscal year 2013 revenue after it recorded $390 million in revenue in fiscal year 2012, which ended on 31 March. The company more than doubled its fiscal 2011 revenue of $186.6 million through the $960 million merger with Elan Drug Technologies (EDT), which combined the firms' complimentary drug delivery technology platforms (scripintelligence.com, 9 September 2011).
Data from a 690-patient, placebo-controlled Phase III clinical trial for aripiprazole lauroxil are anticipated in late 2013. If the data are positive, Alkermes plans to file a new drug application (NDA) with the US FDA in 2014 for the once-monthly schizophrenia therapy, which converts to aripiprazole after injection in the body.
The proprietary compound is a prodrug of the Bristol-Myers Squibb and Otsuka atypical antipsychotic Abilify (aripiprazole), which is dosed daily as both an oral and injectable drug. So with just one Phase III study for aripiprazole lauroxil, Alkermes will leverage existing data for Abilify to seek FDA approval under section 505(b)(2) of the Food, Drug and Cosmetic Act, which allows applicants to submit NDAs that refer to data from previously approved drugs.
Now that the US Patent and Trademark Office has issued a notice of allowance for the company's US Patent Application 12/823,007 and a patent is expected to be issued within the next month, Alkermes has patent protection until at least 2030 for aripiprazole lauroxil.
The new molecular entity was formulated with the company's LinkeRx technology platform for the development of injectable extended-release atypical antipsychotics and other CNS therapies. Aripiprazole lauroxil sits in patients' muscles and slowly metabolizes into aripiprazole.
Pops noted that schizophrenia is a $24 billion pharmaceutical market worldwide and the vast majority of patients are treated with oral agents. Abilify is the top drug in that market.
"We think there's potential for more to be treated with long-acting injectables," he said, especially for patients whose doctors are looking for ways to improve compliance with antipsychotic dosing regimens.
But for patients likely to stick with oral medicines, Alkermes is developing ALKS 3831, which is a combination of the company's proprietary molecule ALKS 33 and olanzapine – the Eli Lilly atypical antipsychotic Zyprexa that was hit by generic competition starting in 2011.
ALKS 3831 is designed to attenuate weight gain and related metabolic side effects associated with antipsychotics, including diabetes and dyslipidemia.
Olanzapine has one of the highest incidences of weight gain and causes some of the largest amounts of weight gain among atypical antipsychotics, according to a 2010 study published in the Cochrane Database of Systematic Reviews.
Pops said the efficacy of olanzapine "comes at a high price for many patients, measured in terms of weight gain and other metabolic changes. It can be 40 or 50 pounds and cause type 2 diabetes or other metabolic disorders."
The difference in weight gain between the ALKS 3831 treatment group and the olanzapine-only control group in a recently completed 106-patient, three-week Phase I clinical trial was statistically significant (p=0.014). Healthy volunteers in the study gained an average of 2.5kg (5.5 lbs) with aripiprazole lauroxil versus 3.4kg (7.5 lbs) with olanzapine.
"They still gained weight, but at a statistically lower level. It's very encouraging," Pops said.
Alkermes will present the early-stage data at an upcoming medical conference and the company plans to begin a Phase II trial with schizophrenia patients in mid-2013. However, Pops said it is too early to say whether ALKS 3831 will follow a 505(b)(2) regulatory path based on known Zyprexa data.
The ALKS 33 component of ALKS 3831 is an opioid modulator in Phase II for the treatment of alcohol dependence. Alkermes noted in July 2011 that ALKS 33 has "durable pharmacologic activity in modulating brain opioid receptors", but the company said it would no longer pursue a binge-eating indication for the molecule (scripintelligence.com, 19 July 2011).
ALKS 33 combined with buprenorphine make up ALKS 5461, which Alkermes views as its third potential CNS blockbuster in addition to ALKS 3831 and aripiprazole lauroxil. ALKS 5461 is in Phase II development for the treatment of major depressive disorder (scripintelligence.com, 4 January 2012).
Alkermes plans to drive home the potential value of its research and development pipeline as it enters into 2013 with continued revenue growth for its established portfolio of more than 20 commercial drug products.
The commercial portfolio is led by Risperdal Consta for schizophrenia and bipolar disorder, Vivitrol for alcohol and opioid dependence, Invega Sustenna (paliperidone palmitate) for schizophrenia, Bristol-Myers Squibb's Bydureon (exenatide extended-release injection) for type 2 diabetes, and Acorda Therapeutics' Ampyra (dalfampridine) to improve walking for people with multiple sclerosis.
Pops said the company's CNS-focused pipeline has "the potential to change the perception and valuation of the company".