lorcaserin

Lorcaserin Carcinogenicity Data Issue

FDA release advisory panel briefing document on Lorcaserin. It raised question regarding carcinogenicity data:

“A number of malignant tumor types developed in rats treated with lorcaserin for up to two years. An excess number of malignant mammary tumors developed in female rats treated with lorcaserin at doses within 7-fold of the proposed clinical dose of 10 mg BID. Male rats developed malignant mammary tumors when treated with lorcaserin at doses 17-fold higher than the proposed clinical dose. ”

This is not entirely surprising to me. I raised this potential pre-clinical data issue after reading an article titled “Arena Pharmaceuticals: Locraserin and the Fallen Competitors: Analysis Part III” (http://www.gekkowire.com/?p=4186 comment by JQ on July 21, 2010).

I found suspension of ATHX-105 development for obesity due to pre-clinical toxicology data interesting since it was supposed to be selective to 5HT2c similar to Lorcaserin. I found the following from ATHX website http://bit.ly/aakDH8):

“In September 2008, we were notified by the FDA that our proposed phase II clinical trial was being placed on clinical hold, pending discussion with the FDA and resolution of several issues, some of which related to proposed trial design, and one of which related to a preclinical toxicology finding in rodents. While we were able to resolve each of the other issues regarding the clinical hold, we believe we will be unable to practically resolve the issue related to the toxicology finding in rodents, and as a result we have suspended further development of ATHX-105. The potential significance of the toxicology issue to humans remains unclear, but it appears to be a compound-specific effect that is not representative of the class of compounds we are developing. However, given that we would have to complete long-term toxicology studies in rodents and potentially other species in order to resolve the issue, and these studies may not be conclusive, we decided that further development of ATHX-105 may be too risky, expensive and time consuming, and therefore may not serve the best interests of our stockholders. Accordingly, we have withdrawn our IND application for ATHX-105, and suspended further development of this compound. ”

Posted on Sept. 14, 2010

accessdata.fda.gov
Belviq (lorcaserin)

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(1R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine

Lorcaserin is a selective 5-HT2C receptor agonist, and in vitro testing of the drug showed reasonable selectivity for 5-HT2C over other related targets. 5-HT2C receptors are located almost exclusively in the brain, and can be found in the choroid plexus, cortex, hippocampus, cerebellum, amygdala, thalamus, and hypothalamus. The activation of 5-HT2C receptors in the hypothalamus is supposed to activate proopiomelanocortin (POMC) production and consequently promote weight loss through satiety. This hypothesis is supported by clinical trials and other studies. While it is generally thought that 5-HT2C receptors help to regulate appetite as well as mood, and endocrine secretion, the exact mechanism of appetite regulation is not yet known. Lorcaserin has shown 100x selectivity for 5-HT2C versus the closely related 5-HT2B receptor, and 17x selectivity over the 5-HT2A receptor.

via wiki

Watch on gfzambrano-blog.tumblr.com

“NEW DIET DRUG HELPS PATIENTS LOSE ABOUT 10% OF WEIGHT”

USAToday reports on the FDA’s recent approval of QYSMIA to combat obesity. The video above highlights the claimed benefits of the newest “weight-loss” pill that will soon be available to millions combating obesity.  It was previously known as QNEXA and did not gain FDA approval under that name when originally considered. At the time, experts were concerned over added risks associated with heart rates. QYSMIA is intended for individuals that are obese, or 30 pounds over their target weight.

Health experts are already cautioning that the pills will not be a ‘magic pill’ that produces results. Rather, as W. Timothy Garvy, Chair of the Department of Nutrition Sciences at the University of Alabama-Birmingham, is quoted as stating, in USAToday:“This is not a magic pill. Patients can’t take it and think that’s all they have to do. It needs to be used with a lifestyle modification program”.

Public Citizen’s Sidney Wolfe has already been outspoken about the newly approved pill and is quoted as stating that it was “reckless” of the FDA to approve it because research has demonstrated it increases heart rate and at least 4 patients taking the pill had non-fatal heart attacks during the research phase.

USAToday reports that post-market surveillance on cardiovascular outcomes is planned but that results will not breadh for 4-5 years. QSYMIA is expected on shelves by the end of 2012.

Zydus Cadila Healthcare Ltd, WO 2015102017, lorcaserin

Zydus Cadila Healthcare Ltd, WO 2015102017, lorcaserin

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Processes for the preparation of lorcaserin Zydus Cadila Healthcare Ltd WO 2015102017, 09 July2015  Applicants: CADILA HEALTHCARE LIMITED [IN/IN]; Zydus Tower, Satellite Cross Roads Ahmedabad – 380 015 Gujarat (IN) Inventors: DWIVEDI, Shriprakash Dhar; (IN). SHAH, Alpeshkumar Pravinchandra; (IN). GAJJAR, Samir Rameshbhai; (IN). KHERA, Brij; (IN)     On 10 May 2012, after a new round of studies…

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Anti-Obesity Drugs: Phentermine-Topiramate Combination

Phentermine/Topiramate Extended Release Preparation is the first FDA approved combination for obesity management. Like Lorcaserin, it is also currently not available in India. The combination works by suppressing appetite and other mechanisms not yet fully understood. At its top dose, it can help patients achieve a mean weight loss of 10.9 % compared to 1.6 % with placebo in 1 year.

Keep reading

Zydus Cadila Healthcare Ltd, WO 2015102017, lorcaserin

Zydus Cadila Healthcare Ltd, WO 2015102017, lorcaserin

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Processes for the preparation of lorcaserin

Zydus Cadila Healthcare Ltd

WO 2015102017, 09 July2015 

Applicants: CADILA HEALTHCARE LIMITED [IN/IN]; Zydus Tower, Satellite Cross Roads Ahmedabad – 380 015 Gujarat (IN) Inventors: DWIVEDI, Shriprakash Dhar; (IN).
SHAH, Alpeshkumar Pravinchandra; (IN).
GAJJAR, Samir Rameshbhai; (IN).
KHERA, Brij; (IN)

On 10 May 2012, after a new round of studies…

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