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New Drugs Online Report for lorcaserin hydrochloride
Information
Generic Name:
lorcaserin hydrochloride 
Trade Name: Lorqess (EU), Belviq (US) 
Synonym: Lorqess 
Entry Type: New molecular entity  
 
Developmental Status
UK: Filing withdrawn 
EU: Filing withdrawn 
US: Launched 
UK launch Plans: Available only to registered users
Actual UK launch date:  
Comments
Jun 13: Launched in the US [32]. 
08/06/2013 09:14:13
May 13: Belviq has been made a Schedule IV controlled substance in the US and the drug will be launched next month [31]. 
08/05/2013 13:35:08
May 13: Company has withdrawn its submission for marketing approval in the EU as it is unable to address all the issue raised in Jan before CHMP make its final decision [30] 
08/05/2013 13:34:34
Jan 13: The company has received the Day 180 List of Outstanding Issues from the EMA´s CHMP. The questions relate to previously identified non-clinical and clinical issues, including tumours in rats, valvulopathy and psychiatric event. These are many of the same concerns about raised in the 120-day list of questions, suggesting Arena´s responses were unsatisfactory [29].  
24/01/2013 15:19:25
Jul 12: The FDA requires Arena to conduct 6 postmarketing studies, including five in different paediatric age ranges. The FDA is also mandating a long-term cardiovascular outcomes trial that will finish in 2018. The company hopes to start this study by mid-2013 [28]. 
08/07/2012 16:29:25
Jun 2012 - US FDA approved lorcaserin hydrochloride as an addition to a reduced-calorie diet and exercise, for chronic weight management [26] 
28/06/2012 10:21:31
May 12: FDA advisory panel vote 18-4 in favor of approval [25]. 
14/05/2012 08:45:52
Mar 12: EMA has accepted for filing [24] 
27/03/2012 15:13:57
The proposed indication is weight control, including weight loss & maintenance of weight loss, in pts who are obese (BMI >30) or overweight (BMI >27) & have at least one weight-related co-morbid condition [23]. 
06/03/2012 09:52:43
Mar 12: Filed in EU [22]. 
04/03/2012 18:09:52
Jan 12: FDA has accepted for filing [21].  
11/01/2012 13:54:24
Jan 12: Company submit response to the FDA´s Complete Response letter [20] 
04/01/2012 14:35:13
Dec 11: Plan to file in EU 1H 2012 [19]. 
06/12/2011 10:05:13
Dec 10: Company expects to resubmit its NDA by end 2011 [17]. 
23/12/2010 08:27:39
Nov 10: Arena & Eisai to review recently presented data from the 1-yr BLOOM-DM study with the FDA [16]. 
12/11/2010 10:36:53
Oct 10: The FDA has issued a Complete Response Letter rejecting approval for lorcaserin. The agency expressed concerns about tumours found in animal studies and the marginal weight-loss seen in non-diabetic patients. It has asked for new data from a one-year study of obese and diabetic patients and asked Arena for independent experts to look at the tumour data [15]. 
26/10/2010 14:13:25
Sep 10: The FDA Endocrinologic and Metabolic Drugs Advisory Committee rejected lorcaserin (votes 5 to 9) on the balance of benefits and risks [14].  
17/09/2010 17:18:58
Jun 10: FDA Endocrinologic and Metabolic Drugs Advisory Committee meeting on 16 Sep 10 will review lorcaserin [11]. 
03/06/2010 10:00:34
Feb 10: FDA decision on licensing expected by 22 Oct 10 [10]. 
27/02/2010 17:42:23
Dec 09: New Drug Application (NDA) submitted to the FDA for lorcaserin, for weight management, including weight loss and maintenance of weight loss. (9) 
23/12/2009 08:34:29
Sep 09: US filing expected in Dec 09 [6] 
19/09/2009 23:09:20
Jun 09: The company expect to file in US by the end of 2009 (5).  
09/06/2009 20:06:41
 
Trial or other data
Jun 12: Public Citizen has written to the FDA urging the agency not to approve lorcaserin because of its association with adverse effects on heart valves [27]. 
07/07/2012 22:59:26
Jun 12: Results from BLOOM-DM published early online: Obesity (2012); 20 7, 1426–1436. doi:10.1038/oby.2012.66 
06/07/2012 16:01:43
May 11: Data from a meta-analyses of three PIII trials investigating presented at the European Congress on Obesity. The trials randomised 7,794 pts, & 7,500 pts were included in the primary efficacy analyses. This was carried out as a Modified Intent-to-Treat with Last Observation Carried Forward (MITT-LOCF) analyses; pts had an average BMI, baseline weight & age of approximately 36 kg/m2, 100 kg & 45 years, respectively & approx 80% were female. At one yr, using MITT-LOCF of the integrated results, 46.3% of lorcaserin 10 mg twice daily & 40.6% of lorcaserin 10 mg once daily pts achieved at least 5% weight loss vs. 22.1% of pts on placebo. 22.0% of lorcaserin 10 mg twice daily pts & 17.3% of lorcaserin 10 mg once pts achieved at least 10% weight loss vs. 8.3% of pts on placebo. Of the pts completing year one of the trials, 62.3% of lorcaserin 10 mg twice daily pts & 52.8% of lorcaserin 10 mg once daily pts achieved at least 5% weight loss vs. 32.0% of pts on placebo. 33.5% of lorcaserin 10 mg twice daily pts & 25.5% of lorcaserin 10 mg once daily pts achieved at least 10% weight loss vs. 13.8% of pts on placebo. The most frequent lorcaserin-associated adverse events included headache, nausea, dizziness, fatigue & dry mouth [18]. 
31/05/2011 09:01:02
Nov 10: top-line results from the one-yr BLOOM-DM trial reported. 604 obese & overweight pts with T2DM were randomised to lorcaserin 10 mg BD, lorcaserin 10mg once daily or placebo. The 3 primary efficacy endpts at wk 52 were proportion of pts losing at least 5% of their baseline body weight, change from baseline in body weight and proportion of pts losing at least 10% of their baseline body weight. Using Modified ITT LOCF analysis, lorcaserin 10 mg BD met the 3 primary efficacy endpts by producing statistically significant weight loss vs. placebo (p<0.0001). At wk 52, 37.5% of pts treated with lorcaserin 10mg BD achieved at least 5% weight loss, vs. 16.1% of pts taking placebo. They achieved mean weight loss of 4.5% (4.7 kg), vs. 1.5% (1.6 kg) for placebo, & 16.3% of lorcaserin 10 mg BD pts achieved at least 10% weight loss, vs. 4.4% of pts taking placebo. Lorcaserin 10 mg BD pts achieved a 0.9% reduction in HbA1c vs. 0.4% reduction for the placebo gp (p<0.0001), but changes with lorcaserin treatment relative to placebo for fasting insulin, triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol, & systolic & diastolic BP were not statistically significant. The most frequent adverse events occurring in ≥10% of pts (excl hypoglycaemia) & the proportion of pts affected for lorcaserin 10 mg BD & placebo, respectively, were: headache (14.5% vs. 7.1%), upper respiratory infection (13.7% vs. 14.7%), back pain (11.7% vs. 7.9%) & nasopharyngitis (11.3% vs. 9.9%). AEs of hypoglycemia were reported by 29.3% & 21.0% of lorcaserin 10 mg BD & placebo patients, respectively. Discontinuations for AEs were 8.6% for lorcaserin 10 mg BD pts and 4.3% for placebo pts. At wk 24, 2.5% of lorcaserin 10 mg BD pts & 1.9% of placebo pts had new valvulopathy detected on echocardiogram; and at wk 52, 2.9% of lorcaserin 10 mg BD pts & 0.5% of placebo pts had new valvulopathy (though the study was not powered to detect meaningful differences in the incidence of valvulopathy) [16]. 
12/11/2010 10:34:39
FDA briefing documents for lorcaserin raise concerns; clinical trials just barely met one of the two common standards for obesity drug effectiveness. Those enrolled in the Bloom trial lost 5.8% percent of their body weight, vs 2.2% in the placebo group. The FDA generally wants weight loss drugs to be 5% points better than placebo. In addition, preclinical data in rats show the drug was linked to "valvular heart disease, neuro-psychiatric and cognitive-related adverse events, and preclinical tumor development," although an increased cancer risk wasn´t apparent in the 7,000 subjects who participated in clinical trials (http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM225631.pdf)  
14/09/2010 21:37:42
Jul 10: PIII BLOOM study results published (NEJM 2010; 363: 245-256). 3,182 obese or overweight adults (mean BMI 36.2) were randomised to receive lorcaserin 10mg, or placebo, twice daily for 52 wks. All pts underwent diet & exercise counselling. At wk 52, patients in the placebo gp continued to receive placebo but pts in the lorcaserin gp were randomised to receive either placebo or lorcaserin. At 1 yr, 55.4% of pts on lorcaserin & 45.1% of pts on placebo remained in the trial, and 1,553 pts continued into yr 2. At 1 yr, 47.5% of pts in the lorcaserin gp & 20.3% in the placebo gp had lost 5% or more of their body weight (p<0.001), corresponding to an average loss of 5.8kg with lorcaserin & 2.2kg with placebo during yr 1 (p<0.001). Among the pts who received lorcaserin during yr 1 & who had lost 5% or more of their baseline weight at 1 yr, the loss was maintained in more pts who continued to receive lorcaserin during yr 2 (67.9%) than in pts who received placebo during yr 2 (50.3%, p<0.001). Among 2,472 pts evaluated at 1 yr & 1,127 evaluated at 2 yrs, the rate of cardiac valvulopathy was not increased with the use of lorcaserin. Among the most frequent adverse events reported with lorcaserin were headache, dizziness & nausea. The rates of serious adverse events in the two gps were similar [13]. 
15/07/2010 18:01:47
Jul 10: Arena has granted Eisai exclusive US rights to commercialize lorcaserin. Arena will manufacture the drug in Switzerland and sell finished product to Eisai for marketing and distribution in the US [12]. 
04/07/2010 16:47:49
Dec 09: Data from a clinical trial evaluating the abuse potential of lorcaserin were presented at the 48th meeting of the American College of Neuropsychopharmacology. The trial was a randomized, placebo-controlled, double-blind, seven-way crossover trial conducted in 35 healthy male and female recreational drug users who received single doses of lorcaserin (20mg, 40mg and 60mg), zolpidem (15mg and 30mg), ketamine (100 mg) and placebo. The primary endpoint was derived from the scores on a "drug liking" scale. Subjects reported neutral "drug liking" scores for placebo and positive "drug liking" scores for zolpidem and ketamine, which confirmed study validity. The subjective effects of lorcaserin 20mg were similar to those of placebo. "Drug liking" was significantly lower for the 40mg and 60mg lorcaserin vs zolpidem and ketamine, and subjects demonstrated significant disliking of these supratherapeutic doses of lorcaserin vs placebo. Subjects´ willingness to take lorcaserin again for recreational purposes was significantly lower for 40mg and 60mg doses vs placebo [8]. 
14/12/2009 11:40:52
Oct 09: Further data relating to secondary outcomes have been reported from the PIII BLOSSOM study. ITT-LOCF analyses showed significant differences between lorcaserin and placebo in reduction in BMI, waist circumference and hip circumference over one year. Lorcaserin was also associated with significant improvements in HDL-cholesterol and triglyceride levels and in QoF measurements using the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) questionnaire. Lorcaserin was well tolerated. AE that exceeded placebo by >3% were headache, nausea, dizziness, fatigue and dry mouth. Serious adverse events occurred infrequently and rates in patients on lorcaserin twice daily, once daily or placebo, respectively, were: 3.1%, 3.4% and 2.2% [7].  
27/10/2009 21:37:22
Sep 09: In the 4008 patient (average BMI 35.9) BLOSSOM one-year study, 47.2% patients on 10mg lorcaserin twice daily lost ≥5% of their body weight vs 25% for those on placebo; 22.6% vs 9.7% lost ≥10% of body weight. This result satisfies the efficacy benchmark in the most recent FDA draft guidance. Average weight loss was 5.9%, 4.8% and 2.8% for patients on lorcaserin 10mg twice daily, once daily or placebo, respectively. Discontinuation rate for adverse events was 7.2%, 6.2% and 4.6%. respectively. Integrated ECG data from BLOSSOM and BLOOM did not identify a risk of valvulopathy with lorcaserin according to criteria requested by the FDA [6]. 
19/09/2009 23:08:10
Jun 09: A poster presented positive results from the BLOOM study’s (n=3,182 , BMI 30-45) per protocol population at the ADA’s 69th Scientific Sessions. 66.4% of lorcaserin patients lost ≥5% of their weight vs 32.1% on placebo (p<0.0001), and 36.2% vs. 13.6% (p<0.0001) ≥10% in year 1. The average weight loss was 17.9lbs vs 7.4 lb. Patients randomized to remain on lorcaserin for year 2 maintained a greater weight loss vs. those who switched to placebo. Results from the BLOSSOM study (n=4,008) are expected in September. Approximately 600 patients are expected to be enrolled in BLOOM-DM, which is planned as a supplement to the lorcaserin US submission for approval (5).  
09/06/2009 20:06:19
Shares in Arena fall and jobs in the company are shed as investors fail to be impressed by the results of BLOOM. The average weight loss (not per protocol) was 5.8% of body weight after 12 months of treatment with lorcaserin vs 2.2% on placebo, a 3.6% difference. The FDA requires a 5% difference. ECG results however do not indicate valvulopathy (3,4) 
25/04/2009 22:38:18
BLOOM results: Lorcaserin patients who completed 52 weeks of treatment according to the protocol lost an average of 8.2% of body weight, or 17.9 pounds, compared to 3.4%, or 7.3 pounds, in the placebo group (p<0.0001) (2).  
31/03/2009 11:05:39
First in new class of drugs 
29/04/2008 15:02:16
Three PIII trials underway (BLOOM, BLOSSOM, BLOOM-DM) (1). Pharmacology similar to fenfluramine; monitoring for cardiac adverse effects are integral to the study design (1). 
29/04/2008 14:59:54
 
Evidence Based Evaluations
EMA doc  http://www.ema.europa.eu/docs/en_GB/document_library/Medicine_QA/2013/05/WC500143811.pdf 
FDA doc  http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM303198.pdf 
NICE scope  http://www.nice.org.uk/nicemedia/live/13036/49715/49715.pdf 
NHSC  http://www.nhsc-healthhorizons.org.uk/files/downloads/1288/1793.dbedf18eb1332734f604bf12edca21e9.pdf 
   
References  
Available only to registered users
Category
BNF Category:
Centrally acting appetite suppressants (04.05.02)
Pharmacology: Serotonin 5HT2Cantagonist  
Epidemiology: In adults, overweight is typically defined by a BMI of 25 kg/m2 to 29 kg/m2 and obesity by a BMI of 30 kg/m2 or more. In 2006, 38% of adults in England were classed as being overweight and 24% as obese [NICE scope].  
Indication: Obesity 
 
Method(s) of Administration
Oral 
 
Company Information
Name: Venseca 
US Name: Eisai 
 
NICE Information
In timetable: Yes  
When:  /  
Note: date TBC - 21st wave, STA [ID337]