August 19, 2013 10:27 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) plans to study Belviq (lorcaserin) in combination with phentermine has met with optimism amongst experts regarding its prospects for additional weight loss. However, experts told Biopharm Insight some safety concerns still linger, particularly in light of the valvulopathy previously observed with the combination fenfluoramine/phentermine (“fen/phen”), they added.
The San Diego, California-based company is partnered with Eisai (TYO:4523) for marketing and distribution of Belviq. The drug was FDA-approved last June to be used alongside a reduced-calorie diet and increased physical activity for chronic weight management.
In a 2Q13 earnings release, the company stated it has completed dosing in a study to evaluate the safety, tolerability and pharmacokinetic properties of Belviq and phentermine when administered in combination. Additionally, plans have been agreed upon with Eisai to initiate a 12-week pilot study to evaluate the co-administration of the two drugs, according to the release.
An Arena spokesperson declined to comment beyond what was discussed in the recent earnings call.
Good prospects for added efficacy
For weight loss, it is pretty clear that using one drug may not be enough for a lot of patients, said Dr Sun Kim, assistant professor in endocrinology, gerontology and metabolism, Stanford University School of Medicine, California. Most drugs, on average, do not produce more than 10% weight loss, but combining modalities with different mechanisms of action would likely produce added weight loss, she said. “I have no problems with trying different combinations because I don’t think we’ve exhausted the ways we can try to control appetite and eating,” she added.
Additional weight loss benefit is expected with the addition of phentermine to Belviq, agreed Dr Caroline Apovian, director, Clinical Research at the Obesity Research Center of Boston Medical Center, Massachusetts. The total weight loss effect will probably be along the lines of fen/phen, she added. In the 1980s, studies of fen/phen yielded a 32-pound average weight loss, according to public information. The average weight loss during the first year on Belviq was about 12 pounds.
It is a good idea to combine Belviq and phentermine, as weight loss drugs will likely be used in combination, said Dr Louis Aronne, directors, Comprehensive Weight Control Program at New York Presbyterian/Weill Cornell Medical Center.
It is a “no brainer” to study Belviq and phentermine in combination, and it will probably increase weight loss, said Dr Donna Ryan, associate executive director for Clinical Research, Pennington Biomedical Research Center, Louisiana. There is a lot of scientific rationale for using drug combinations for obesity, similar to how most people being treated for hypertension are often on two or three different blood pressure-lowering medications, she said. Multiple medications at lower doses can produce increased efficacy with decreased side effects as the drugs are much more tolerable at lower doses, she said.
Studying Belviq in combination with phentermine is an obvious next step, said Dr Steven Smith, scientific director of the Florida Hospital-Sanford-Burnham Translational Research Institute. Generally, when combining obesity medications, there is at least an additive, if not synergistic effect between the drugs, he said. The concept of serotonergic agents (drugs related to the neurotransmitter serotonin) being combined with a drug like phentermine which has more of an adrenergic effect (having to do with adrenaline) makes a lot of sense from a mechanistic standpoint now that there is a greater appreciation for the role of the brain in appetite, he said. Agents that influence serotonin in combination with sympathomimetic agents like phetnermine makes a lot of sense, he added.
Some safety concerns linger
One concern about Belviq and phentermine would be that it could encounter the same issues as fen/phen, specifically the valvular concern, said Kim. Even with Belviq, there are still some lingering questions regarding its effect on cardiac valves. It is important not to add in additional problems along with the beneficial effects of weight loss, she said.
Aronne however downplayed valvular concerns, as fenfluoramine was ultimately implicated in the fen/phen valvular issues. Phentermine was “completely exonerated” from the valvular issues, and Belviq has been thoroughly studied for any CV concerns, he said. There is about as high a degree of certainty as possible that there will not be a CV side effect linked to Belviq, he added.
Belviq is not fenflouramine, Apovian said, noting she does not foresee valvulopathy as being a major issue. Valvulopathy is also associated with obesity, therefore it is important to measure baseline valvulopathy and track it in a clinical trial setting to rule out Belviq-related effects, she explained.
Ryan agreed the valvulopathy issue is pretty well understood, and also was due to fenfluoramine rather than phentermine. Specifically, the 5HT2b receptor mediated the heart valve effects from fenfluoramine, whereas Belviq is highly specific for the 5HT2c receptor, and avoids the 2b receptor, she explained. Further, Belviq does not require patient echocardiograms prior to initiating treatment, speaking favorably toward Belviq’s CV profile, she added.
The pharmacologies of Belviq and fenfluoramine are very different, said Smith. Belviq was designed to get around the lack of specificity of generic serotonergic activators -- like fenfluoramine -- and only hit the 5HT2c receptor, he noted.
Approximately 12,500 Belviq prescriptions were filled in the US between 11 June and 19 July, according to IMS Health. Company revenues in 2Q13 totaled USD 68.9m, including USD 1.3m in net product sales and USD 65.5m in milestone payments, according to a company press release.
Arena has a market cap of USD 1.6bn.
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