October 19, 2012 9:28 pm
This article is provided to FT.com readers by BioPharm Insight—a news service focused on providing insight into the most price sensitive issues in the global pharmaceutical market. www.biopharminsight.com
Arena Pharmaceuticals’ (NASDAQ:ARNA) likely Drug Enforcement Agency (DEA) scheduling for anti-obesity drug Belviq (lorcaserin) is unlikely to impact prescribing habits, experts told BioPharm Insight. While schedule IV classification is likely, experts are not concerned the drug will be addictive in patients.
At the time of approval, the US Food and Drug Administration (FDA) recommended schedule IV; schedule V is the lowest possible DEA schedule.
Arena is partnered with Eisai (TYO:4523) for the commercialization of Belviq in the US. Eisai is currently targeting an early 2013 Belviq launch, pending the finalization of DEA scheduling, according to an Arena spokesperson. The DEA is in its review process, and once the DEA finalizes Belviq’s scheduling designation, Eisai will make the drug available to patients and physicians in the US, the spokesperson said.
The FDA approved Belviq 27 June for chronic weight management in obese adults and overweight adults with at least one weight-related medical condition. The Centers for Disease Control and Prevention (CDC) define obesity based on body mass index (BMI), a measure determined by weight and height. In adults, a BMI between 25 and 29.9 is considered overweight, while a BMI of 30 and above is defined as obese.
More than one-third of US adults (35.7%) are obese, according to the CDC. In 2008, medical costs associated with obesity were USD 147bn, the CDC estimated.
DEA scheduling impact
At the time of approval, Arena was instructed to conduct six post-marketing studies including a long-term cardiovascular outcomes trial and five pediatric trials, the first of which must be in juvenile rats.
Fellow anti-obesity drug developer Vivus (NASDAQ:VVUS) followed close on Arena’s approval, winning an FDA nod for Qsymia on July 18. Qsymia is a new extended-release formulation of the drugs phentermine and topiramate, which are available as generics. While phentermine has schedule IV status, Qsymia is not DEA scheduled.
Because Belviq is a new drug, unlike the generic drugs that comprise Qsymia, it will be scheduled while Qsymia is not, said Dr Caroline Apovian, director, Clinical Research at the Obesity Research Center of Boston Medical Center. It is a foregone conclusion Belviq will receive a schedule IV classification, said Dr Donna Ryan, executive director for clinical research, Pennington Biomedical Research Center, Louisiana.
The schedule IV classification is unlikely to hinder sales, Apovian said, noting it has never bothered her to use a scheduled drug. Ryan agreed, adding the designation is “not a big deal” and “just a line to fill in on the prescription.”
Belviq does not have any real problems with abuse, said Dr Frank Greenway, professor and director, outpatient clinical research, Pennington Biomedical Research Center, Louisiana. Schedule IV allows regulators to keep track of doctors’ prescribing habits, Greenway added, noting the scheduling does not make it more difficult to write prescriptions.
The difference between schedule IV and schedule V is “negligible,” said obesity consultant Ted Kyle, ConscienHealth, Pittsburgh. Codeine cough syrups are schedule V and dispensed without a prescription, but requiring a signature, he noted.
The schedule IV classification makes sense, said Kyle, as it seems Belviq has low abuse potential, comparable to that of Ambien (zolpidem), which is also a schedule IV controlled substance. Ambien and Xanax (alprazolam) are examples of schedule IV drugs that are widely used, he added.
Both Ryan and Kyle noted the designation reflects added caution from the FDA. Ryan said the schedule IV designation has nothing to do with abuse and dependence but because the FDA wants obesity agents to be used responsibly and not for cosmetic weight loss.
European approval prospects
Prospects for Belviq’s speedy EU approval remain low considering the European Medicines Agency’s (EMA’s) harsh stance on drug therapy for a condition largely viewed as a psychobehavioral disease, rather than a risk factor for hypertension and diabetes, experts said.
EMA is thus likely to scrutinize the agent’s modest weight-loss effects, they added. In final clinical assessments, Belviq demonstrated an approximately 3% placebo-adjusted weight-loss effect, while Qsymia revealed close to a 10% placebo-adjusted weight loss. Placebo-adjusted percentage refers to the percentage of weight loss seen in patients treated with the respective drug minus the percentage of weight loss in placebo patients.
EU regulators will likely delay Belviq approval at least several months as US post-marketing and cardiovascular data become available, the experts said.
Belviq, a serotonin 2C receptor agonist, targets the same appetite pathway as the infamous “fen-phen” drug combination (fenfluramine/phentermine). Both drugs act through a serotonin mechanism, but fenfluramine was associated with heart valve disease and withdrawn from the market in 1997.
While Belviq is related to fenflouramine, it has a more favorable safety profile and has not demonstrated valvular issues thus far, an ex-US Vivus consultant noted. However, valve problems cannot be discounted as the signal with fen-phen was not picked up until there were millions of patient exposures, the consultant said.
Because of superior safety, Belviq may face less of an EU approval delay compared to Qsymia, some experts said, noting Qsymia’s potential negative effects on blood pressure. However, one expert noted, Belviq’s similarity to Abbott Laboratories’ (NYSE:ABT) Meridia (sibutramine) may mean a pre-approval cardiovascular outcomes trial will be required, potentially delaying approval by a few years.
Meridia was withdrawn from the market after demonstrating adverse effects including death, nonfatal stroke and nonfatal heart attack.
The European Medicines Agency’s Committee for Medicinal Products for Human Use recently recommended against Qsymia approval due to the potential for cardiovascular and neuropsychiatric adverse effects.
Belviq is currently under regulatory review in the EU, an Arena spokesperson said. The company has received the 120-day assessment report and list of questions, she added. Arena plans to respond this quarter and expects a decision in 1H13, the spokesperson noted.
Belviq is estimated to have US annual sales of USD 624m in 2017, according to BioPharm Insight data.
Arena has a current market cap of USD 2.1bn.
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