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Lupus Clinical Trials

New Medical Therapies™

Obesity

December 2, 2013

Zafgen released results of a phase II study of beloranib for the treatment of obesity in 147 subjects over 12 weeks. The randomized, double-blind, placebo-controlled trial included mostly obese women with mean age 48.4 years, body weight (BW) 100.9kg, and body mass index (BMI) 37.6kg/m2, who were enrolled into one of the four arms of the trial (N=37 in 0.6mg, 37 in 1.2mg, 35 in 2.4mg and 38 in placebo arm). Subjects on 0.6mg, 1.2mg or 2.4mg of beloranib lost on average (+/- standard error of mean) -5.5 +/- 0.5kg, -6.9 +/- 0.6kg, and -10.9 +/- 1.1kg, respectively, v. -0.4 +/- 0.4kg for those on placebo (all p<0.0001 v. placebo). Weight loss with beloranib was progressive and continuing at week 12, reduced sense of hunger and improved cardiometabolic risk markers. Clinically and statistically significant improvements in systolic blood pressure were observed for the 1.2mg and 2.4mg doses, showing reductions of 7.6mmHg and 12.0mmHg, respectively.

October 21, 2013

Kythera Biopharmaceuticals issued results of two phase III clinical trials of ATX-101 for the reduction of submental fat, which commonly presents as a double chin. Studies ATX-101-11-22 and ATX-101-11-23 are two identical, multicenter, double- blind, randomized, placebo-controlled phase III trials conducted to compare the efficacy and safety of a 2mg/cm2 dose of ATX-101 v. placebo for the reduction of submental fat. Patients received up to six treatments approximately 28 days apart. The studies were conducted at 70 centers in the U.S. and Canada and enrolled 506 and 516 subjects with moderate-to-severe submental fat at baseline as determined through both validated clinician- and patient-rating scales. Clinician ratings demonstrated that 79.5% of ATX-101-11-22 and 78.3% of ATX-101-11-23 subjects showed an improvement of at least one grade using the validated Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) assessed 12 weeks after the last treatment v. 36.4% and 34.6%, respectively, for placebo.

June 3, 2013

Novo Nordisk issued results from a phase IIIa trial of liraglutide for the treatment of obesity. This double-blind, randomized study enrolled 3,731 obese or overweight patients with co-morbidities such as prediabetes, hypertension and dyslipidaemia, but without diabetes. Subjects received liraglutide 3mg in combination with diet and exercise for 56 weeks, or placebo. Results showed from mean baseline weight of 106kg and a BMI of 38kg/m2, the average weight loss for people treated with liraglutide 3mg at 56 weeks was 8.0% compared to 2.6% for people treated with placebo. The proportion of people achieving a weight loss of at least 5% was 64% for liraglutide 3mg and 27% for placebo. The proportion of people achieving a weight loss of at least 10% was 33% for liraglutide 3mg and 10% for placebo treatment. All differences between liraglutide and placebo were statistically significant and the trial met all three co-primary endpoints. In addition, people treated with liraglutide 3mg experienced statistically significant improvements in obesity-related risk factors, including blood pressure, cardiovascular risk biomarkers, lipids and patient-reported quality of life, compared to people treated with placebo. The drug was well tolerated. The most frequent adverse events were related to the gastrointestinal system and diminished over time. Novo Nordisk expects to complete the remaining phase IIIa trial in the SCALE program in the third quarter of 2013 and to file liraglutide 3mg for regulatory review as a treatment for obesity in the U.S. and E.U. at the beginning of 2014.

October 1, 2012

Zafgen issued results from a phase Ib trial of beloranib for the reduction of body fat, rapid weight loss and improvements in cardiovascular disease risk in obese females. This randomized, double-blind, placebo-controlled study enrolled obese women with a mean (SEM) age of 45.7 years, body weight of 104.9kg and BMI of 39.5kg/m2. Subjects were randomized into three arms and received beloranib 3.0mg or 6.0mg, or placebo, twice weekly for four weeks. Patients were allowed to eat normally and were not counseled to change their exercise habits. After four weeks, subjects on 3.0mg beloranib lost an average of 4.7kg from baseline (p=0.0008), 6.0mg beloranib lost 6.7kg (p=0.0013) and placebo-dosed subjects gained an average of 0.2kg. Body composition measurements were consistent with reduced adipose tissue mass. Despite the fact that they lost weight, hunger tended to be reduced (-28% with 3.0mg, -52% with 6.0mg, -2% with placebo). Blood pressure (BP) and glucose did not change with treatment. The drug was well tolerated. The most frequent adverse events were mild diarrhea, nausea, headache, dizziness, infusion site injury and sleep disturbance. Based on these data, Zafgen will expand its clinical development program to include more subjects.

January 10, 2011

Zafgen issued positive results from a phase Ib trial of ZGN-433 for the treatment of severe obesity. This double-blind, placebo-controlled multiple ascending dose study enrolled 24 severely obese females with a body mass index between 32-45 and co-morbidities. The subjects received ZGN-433 or placebo by intravenous administration twice weekly over a four-week period at three different dose levels (0.22, 0.65, and 1.96 mg per administration). They were allowed to eat normally and were not counseled to exercise. The primary and secondary endpoints were both reached. ZGN-433 at a dose of 0.9 mg/m2 was well tolerated and reduced body weight by a median value of 1 kg per week and 3.1% over 26 days relative to placebo. The results also demonstrated a decline in hunger as well as meaningful changes in lipid parameters following treatment at 0.9 mg/m2. No treatment-related serious adverse events were observed.

November 15, 2010

Arena Pharmaceuticals and Eisai released positive results from a phase III trial of lorcaserin for obesity and type II diabetes. This trial, dubbed BLOOM-DM, enrolled 604 obese and overweight subjects with type II diabetes who were randomized to lorcaserin 10 mg twice daily (BID), lorcaserin 10 mg dosed once daily (QD) or placebo. To expedite enrollment, randomization to the lorcaserin 10 mg QD dose was discontinued after approximately 300 patients were enrolled in the trial. The trial had three primary efficacy endpoints at Week 52: the proportion of patients who lost at least 5% of their baseline body weight; change from baseline in body weight; and the proportion of patients who lost at least 10% of their baseline body weight. All three endpoints were reached with lorcaserin 10 mg BID by producing statistically significant weight loss compared to placebo (p<0.0001). At Week 52: 37.5% of subjects in the lorcaserin arm achieved at least 5% weight loss compared to 16.1% of the placebo arm; subjects treated with lorcaserin achieved mean weight loss of 4.5% (4.7 kg), compared to 1.5% (1.6 kg) for placebo and 16.3% of the lorcaserin arm achieved at least 10% weight loss, compared to 4.4% of the placebo arm.

October 5, 2009

Orexigen issued positive results from phase IIb trial of Empatic for the treatment of obesity. This 24-week, randomized, double-blind, placebo-controlled trial, dubbed ZB-202, enrolled 729 generally healthy, non-diabetic obese subjects at 20 sites in the US. The subjects were placed in one of six treatment groups: placebo, one dose of bupropion monotherapy, two doses of zonisamide monotherapy and two doses of Empatic. The primary endpoint was percent change in body weight after 24 weeks for Empatic compared to its individual components and placebo. The subjects who received Empatic360 therapy lost 9.9% of their baseline body weight (22 lbs) compared to 1.7% for placebo (p<0.001). Of subjects who completed 24 weeks of therapy on Empatic360, 82.6% lost at least 5% of their baseline body weight and 47.7% lost at least 10% of their baseline body weight compared to 18.9% and 5.7% of the placebo group, respectively (p<0.001 for both). Mean weight loss for Empatic360 was 7.5% versus 2.3% for bupropion 360 and 5.3% for zonisamide 360 (p<0.001). Mean weight loss for Empatic120 was 6.1% versus 2.3% for bupropion 360 and 3.2% for zonisamide 120 (p<0.001). In addition, the subjects treated with Empatic experienced significant weight loss as early as their first post-baseline visit at week four. This weight loss continued through the end of the trial period, with no evidence of a weight loss plateau.

September 28, 2009

Arena issued positive results from a phase III trial of lorcaserin for the treatment of obesity. This double-blind, randomized, placebo-controlled trial, dubbed BLOSSOM (Behavioral modification and Lorcaserin Second Study for Obesity Management), enrolled 4008 subjects. The population included obese subjects (BMI 30 to 45) with or without co-morbid conditions and overweight subjects (BMI 27 to less than 30) with at least one co-morbid condition. The subjects received 10 mg of lorcaserin dosed once (QD) or twice daily (BID) or placebo over a one-year treatment period. In the subjects treated with 10 mg of lorcaserin BID who completed the 52-week trial, 63.2% lost at least 5% of their body weight and 35.1% lost at least 10% of their body weight (p<0.0001 for both vs. placebo). Subjects in this arm lost an average of 17.0 pounds, or 7.9% of their body weight. In the subjects treated with 10 mg of lorcaserin QD and completing the 52-week trial, 53.1% lost at least 5% of their body weight and 26.3% lost at least 10% of their body weight (p<0.0001 for both compared to placebo). The average weight loss in this treatment arm was 14.3 pounds, or 6.5%. The top quartile of the lorcaserin-treated patients lost 36% more body weight than the top quartile of placebo patients. Lorcaserin was very well tolerated. Echocardiographic evaluations showed no association between lorcaserin and the development of heart valve insufficiency

September 14, 2009

Vivus reported positive results from two randomized, double-blind, placebo-controlled phase III trials of Qnexa for the treatment of obesity. The first trial, EQUIP (OB-302), enrolled 1,250 morbidly obese adult subjects with an average baseline BMI of 42.1 kg/m(2) and baseline weight was 256 pounds. The subjects received once daily treatment with low dose Qnexa, full strength Qnexa or placebo. During the first 4 weeks of treatment, study medication was titrated to the assigned dose level than maintained at this level through Week 56. The subjects also followed a mild hypocaloric diet representing a 500-calorie/day deficit. Of the 1,250 enrolled subjects, 680 completed the study. The mean weight loss was 2.5%, 7.0% and 14.7% for the placebo, low dose and full dose Qnexa arms, respectively (p<0.0001 for both arms vs. placebo). Weight loss of 5% of more occurred in 26%, 59% and 84% of the placebo, low dose and full dose Qnexa arms, respectively (p<0.0001 for both arms vs. placebo). The second trial, CONQUER (OB-303), enrolled 2,487 subjects with an average baseline BMI of 36.6 kg/ m2 and baseline weight was 227 pounds. The subjects received once daily treatment with mid-dose Qnexa, full-dose Qnexa or placebo for a 4-week dose titration period followed by 52 weeks of treatment. They also followed a mild hypocaloric diet representing a 500-calorie/day deficit. Of the 2,487 subjects enrolled, 1,542 completed the study. The mean weight loss was 2.4%, 10.5% and 13.2% for the placebo, mid-dose and full dose Qnexa arms, respectively (p<0.0001 for both arms vs. placebo). Weight loss of 5% of more occurred in 26%,75% and 85% of the placebo, mid-dose and full dose Qnexa arms, respectively (p<0.0001 for both arms vs. placebo). Treatment was well tolerated.

July 27, 2009

Amylin reported positive results from a phase IIb trial of pramlintide plus metreleptin for the treatment of obesity. This 28-week, double-blind, placebo-controlled multi-center study enrolled 608 obese or overweight subjects with a BMI ranging from 27-45 kg/m2. Following a one-week placebo lead-in period, subjects were randomized to receive twice-daily therapy with one of the following eight treatment regimens: 1) placebo/placebo; 2) pramlintide 360 mcg/placebo; 3) metreleptin 5 mg/placebo; 4) pramlintide 180 mcg/metreleptin 2.5 mg; 5) pramlintide 180 mcg/metreleptin 5 mg; 6) pramlintide 360 mcg/metreleptin 1.25 mg; 7) pramlintide 360 mcg/metreleptin 2.5 mg; or 8) pramlintide 360 mcg/metreleptin 5 mg. At 28 weeks, evaluable subjects with a starting body mass index less than 35 kg/m2 (n≡149), and treated with the highest pramlintide/metreleptin doses, experienced significantly more weight loss on average (11%; 22 pounds, p<0.01) than those receiving placebo (1.8%; 4 pounds) or either agent alone (approximately 5%; 10 pounds). The combination therapy was well tolerated, and no cardiovascular or neuropsychiatric adverse events were observed.

April 6, 2009

Arena released positive results from a phase III trial of lorcaserin for the treatment of obesity. This double-blind, randomized, and placebo-controlled trial, dubbed BLOOM (Behavioral modification and Lorcaserin for Overweight and Obesity Management) enrolled 3,182 obese or overweight subjects across several sites in the US. The subjects received lorcaserin (10 mg dosed twice daily) or placebo over a two-year treatment period. At Week 52, 856 subjects in the lorcaserin arm were re-randomized to continue lorcaserin or to switch to placebo, and 697 subjects remained on placebo treatment. All subjects received echocardiograms at baseline and follow-up echocardiograms at 6, 12, 18 and 24 months. The co-primary efficacy endpoints were: the proportion of subjects achieving 5% or greater weight loss after 12 months, the difference in mean weight loss compared to placebo after 12 months, and the proportion of subjects achieving 10% or greater weight loss after 12 months. Statistical significance was achieved on all three of the primary endpoints versus placebo (p<0.0001). The subjects treated with lorcaserin who completed 52 weeks of treatment lost an average of 8.2% of body weight, compared to 3.4% in the placebo group (p<0.0001). Based on assessment of echocardiograms performed at baseline and follow-up, lorcaserin met the primary safety endpoint of no significant difference in rates of valvulopathy at 12 months. Treatment was generally very well tolerated.

February 19, 2009

Shiongi issued positive results from two phase II trials of velneperit for the treatment of obesity. The two double-blind, placebo controlled studies enrolled 1,566 obese subjects across the US. The studies were designed to examine the safety and effectiveness of long-term velneperit treatment under different diet conditions, the Reduced Calorie Diet (RCD) and Low Calorie Diet (LCD). The RCD study began with a six-week run-in, consisting of an 800 kcal/day reduction in the amount of food required to maintain the starting body weight. Thereafter, subjects were randomized to placebo, 800mg or 1600mg of velneperit once daily in conjunction with the same 800 kcal/day reduction in daily food intake, for an additional 54 weeks. In the LCD study, subjects were randomized to one of three treatment groups for a period of 60 weeks. All treatment groups were in conjunction with a fixed low calorie diet of 950 kcal/day. The first group received placebo in conjunction with the fixed low calorie diet for six weeks, followed by placebo with a reduced calorie diet identical to that of the RCD study for 54 weeks (placebo/placebo). The second group received placebo in conjunction with the fixed low calorie for six weeks, followed by 54 weeks of 1600mg velneperit once-daily with the same reduced calorie diet as that of the RCD study (placebo/velneperit). The third group received 1600mg velneperit once-daily in combination with the fixed low calorie diet for six weeks, followed by 54 weeks of 1600mg velneperit once-daily combined with the same reduced calorie diet as that of the RCD study (velneperit/velneperit). The primary endpoint was a statistically significant reduction in body weight. In the RCD study the 800mg velneperit treatment group was the most effective dose. Subjects lost 3.8 kg of their baseline body weight after the six-week reduced calorie diet run-in period, versus 0.8 kg for the placebo group (p-value <0.0001). The percentage of weight lost during the 54-week period was 3.9% for the 800mg velneperit treatment group versus 0.9% for the placebo group (p-value<0.0001). The percentage of responders (loss of greater than or equal to 5% of baseline weight) in the 800mg velneperit treatment group was 35% versus 12% in the placebo group (p-value<0.0001). In the LCD study, the most effective treatment group was placebo/velneperit , in which subjects lost 7.1 kg of their baseline body weight versus 4.3 kg for the placebo/placebo group (p-value<0.0001). The percentage of weight lost during this 60-week period was 6.9% for the placebo/velneperit treatment group versus 4.4% for the placebo/placebo group (p-value<0.0002). The percentages of responders in the placebo/velneperit treatment group was 52%, versus 35% for the placebo/placebo group (p-value<0.0001). Velneperit was well tolerated in all treatment groups. Based on the results, Shiongi plans to move forward with the development of velneperit.

February 16, 2009

Genaera issued positive preliminary results from a phase Ib trial of trodusquemine for the treatment of type II diabetes and obesity. This placebo controlled, multiple ascending dose study, dubbed Study 102, planned to enroll 21 obese type II diabetic subjects. The subjects will receive three dose levels (3, 6, and 10 mg/m2) of trodusquemine or placebo every three days over a 21 day period. The primary endpoints are safety and multiple dose pharmacokinetics. Secondary outcomes include oral glucose tolerance and insulin sensitivity, satiety and weight loss. Data are from the first cohort (eight doses of 3 mg/m2 over 21 days). Treatment with trodusquemine led to a 9.5% decrease in fasting blood glucose, a 7% decrease in the area under the curve during the oral glucose tolerance test; an 11.3% decrease in serum fructosamine, which is used to monitor short-term (2-3 weeks) blood sugar control; and a 0.4% decrease in hemoglobin A1C (HbA1C), used to monitor longer-term (2-3 months) blood sugar control. Treatment was well tolerated, with no serious adverse events or dose-limiting toxicities reported.

January 19, 2009

Orexigen issued positive results from a phase III trial of Contrave for the treatment of obesity. This randomized, double-blind, placebo control, parallel assignment trial, dubbed NB-302 enrolled 793 subjects in the US. The subjects received Contrave (32mg naltrexone SR/360mg bupropion SR) or placebo, in combination with intense diet, exercise and behavior modification, for 56 weeks. The primary endpoint was change from baseline to week 56 in percentage of total body weight lost. In the Contrave treatment arm, subjects lost an average of 17.6 pounds, or 8.1% of their baseline body weight, versus 10.6 pounds, or 4.9% of baseline body weight for placebo (p<0.001). In addition, the percentage of subjects who lost greater than or equal to 10% of their body weight was 41.5% in the Contrave group compared to 20.2% in the placebo group (p<0.001). Contrave also demonstrated clinically and statistically significant improvements over placebo including HDL, triglycerides, waist circumference and hsCRP, markers of cardiovascular risk. Treatment was generally well tolerated. Three additional phase III trials are currently underway.

December 15, 2008

Arena Pharmaceuticals released positive results from a phase IIb trial of lorcaserin for the treatment of obesity. This randomized, double-blind, placebo-controlled study enrolled 469 subjects with a Body Mass Index ranging from 30 to 45, in the United States. The subjects received lorcaserin 10 mg once daily, 15 mg once daily, or 10 mg twice daily or placebo for 12 weeks. The primary efficacy endpoint was a reduction in weight from baseline at the end of 12 weeks. The subjects who were treated with lorcaserin achieved progressive, dose-dependent and statistically significant weight loss of 4 pounds (1.8 kg), 5.7 pounds (2.6 kg) and 7.9 pounds (3.6 kg) at daily doses of 10 mg, 15 mg and 20 mg (10 mg twice daily), respectively, compared to weight loss of 0.7 pounds (0.3 kg) for placebo (p<0.001 for each group). A statistically significant percentage of subjects treated with lorcaserin who completed the study lost greater than or equal to 5% of their weight from baseline: 12.8%, 19.5% and 31.2% in the 10 mg, 15 mg and 20 mg groups, respectively, compared to 2.3% of those on placebo. The dose with the highest degree of efficacy was 20 mg, with more than 90% of subjects achieving some level of weight loss. In addition, total cholesterol and waist circumference were significantly decreased by the two highest lorcaserin doses.

August 13, 2008

Genaera reported positive interim results from a phase I trial of trodusquemine for the treatment of obesity. This double-blind, randomized, placebo-controlled, single ascending dose trial had enrolled 28 healthy, obese subjects to date. Pharmacokinetic data showed a predictable pattern with minimal subject-to-subject variability and linearity across the range of doses studied. Treatment has been well tolerated, with no reported adverse events. Genaera is continuing this trial in order to determine the maximum tolerated dose and establish dose-limiting toxicity and proof-of-concept. Full results are expected by the end of 2007.

April 7, 2008

Merck reported positive interim results from a phase III trial of taranabant for the treatment of obesity. This two-year, multinational, double-blind, randomized, placebo-controlled study enrolled two thousand and five hundred subjects with a Body Mass Index (BMI) between 27 kg/m and 43 kg/m. Following a two-week, single-blind, placebo plus diet (25 percent calorie reduction) run-in period, subjects were randomized to receive placebo, taranabant 2 mg, 4 mg or 6 mg once daily for up to one hundred and four weeks, with continued diet and exercise. During the study, subjects taking the taranabant 6 mg dose were re-randomized to receive placebo or taranabant 2 mg (ratio 1:2) following a recommendation by an independent external Data Safety Monitoring Committee. The primary endpoints were the change in body weight from baseline at fifty two weeks and the change in the proportion of subjects with at least five percent and ten percent reduction in body weight at fifty two weeks for both taranabant 2 mg and 4 mg. The subjects in the taranabant 2 mg experienced more than double the amount of weight loss at fifty two weeks compared to patients treated with placebo, with a mean weight loss reduction from baseline of 6.6 kg compared to 2.6 kg (p<0.001). Maximum weight loss was achieved by week thirty six and was maintained throughout the next sixteen weeks. In addition, at fifty two weeks more than two times as many subjects treated with taranabant 2 mg (57%) lost five percent of their baseline body weight compared with 27% of the subjects on placebo (p<0.001). More than three times as many subjects treated with taranabant 2 mg (28%) lost ten percent of their baseline body weight compared with 8% of the subjects on placebo (p<0.001). Treatment was determined to be well tolerated. Based on the results. Merck plans to continue to evaluate taranabant in doses up to and including 2 mg in upcoming phase III studies.

November 26, 2007

Novo Nordisk released positive results from a phase II trial of liraglutide for the treatment of obesity. This trial enrolled 564 subjects with an average baseline weight of just below 100 kg. Following a two-week run-in period, the subjects were randomized to receive placebo, increasing doses of liraglutide or to an open-labeled control arm with orlistat, for a treatment period of twenty weeks. Results showed that liraglutide given once daily at the highest dose led to a weight loss from baseline of just above 7 kg, compared to a weight loss of just above 4 kg in the orlistat arm and a weight loss of just below 3 kg in the placebo arm. All tested doses of liraglutide reduced body weight; more than 75% of those treated with the highest dose experienced a weight loss larger than 5%, and more than 25% experienced a weight loss larger than 10% relative to their baseline body weight. In addition, prediabetes symptoms were observed in approximately 30% of all the subjects at baseline. After twenty weeks of treatment with any dose of liraglutide, between 80% and 90% of these subjects no longer showed signs of prediabetes, compared to 40% in the placebo- and orlistat-treated groups. Based on the results Novo Nordisk plans to move forward with the development of liraglutide for the treatment of obesity.

November 19, 2007

Amylin reported positive results from a phase IIa trial of pramlintide in combination with metreleptin for the treatment of obesity. This randomized, double-blind, active-drug-controlled study enrolled 177 obese subjects with a body mass index ranging from 27 to 35 kg/m2. For the initial four weeks of the study all subjects received pramlintide (180 micrograms twice daily for two weeks, followed by 360 micrograms twice daily for two weeks). Those who completed this period and lost two to eight percent of their body weight were eligible to continue in the study (n=139). These subjects were randomized to receive with twice daily injections of pramlintide (360 micrograms) with metreleptin 5 mg); pramlintide (360 micrograms) with placebo; or metreleptin (5 mg) with placebo. Results revealed that the pramlintide/metreleptin treatment reduced body weight on average by 12.7%, significantly more than treatment with pramlintide alone (8.4%; p<0.001). Subjects treated with pramlintide/metreleptin lost an average of twenty-five pounds from study start compared with an average of seventeen pounds for subjects treated with pramlintide alone. The weight loss in the pramlintide/metreleptin combination arm continued through to the end of the study, while weight loss in the other arms stabilized towards the end of the study. Treatment was generally well tolerated, with adverse events mild to moderate in nature. Based on the results, Amylin plans to move forward with the development of this combination treatment.

November 5, 2007

Epix reported positive results from a phase Ib trial of PRX-07034 for the treatment of obesity. This randomized, double-blind, placebo-controlled study enrolled twenty-one obese, but otherwise healthy, adult subjects. The subjects received PRX-07034 (600 mg) administered orally twice daily for twenty-eight days. After twenty-eight days, the average reduction in weight was 1.82 kg; (p less than 0.005). After forty-two days, subjects on PRX-07034 lost an average of 0.26 kg overall compared to an average of 1.25 kg gained by subjects on placebo (p less than 0.005). Overall, only one of the subjects on placebo (10%) lost weight during the trial, compared to seven of the eleven subjects on PRX-07034 (64%). PRX-07034 was associated with a significant reduction in serum leptin levels, a marker of fat stores in the body (p<0.036). Treatment was determined to be safe and well tolerated, with no serious adverse events reported. Based on the results, Epix plans to move forward with the development of PRX-07034.

October 29, 2007

Genaera announced positive results from a phase I trial of trodusquemine for the treatment of obesity. This double-blind, randomized, placebo-controlled, single-group assignment, dubbed MSI-1436C-101, enrolled 35 obese subjects (body mass index of 27-40). The subjects were placed in five sequential dosing groups and received a single intravenous dose of trodusquemine or placebo. Treatment was determined to be safe and well tolerated, with no reported serious adverse events. The pharmacokinetic profile showed a consistent pattern with minimal subject-to-subject variability and linearity across the range of doses studied. The maximum tolerated dose was determined to be 40 mg/m2. Based on the results, Genaera plans to advance the development of trodusquemine.

September 24, 2007

Vernalis announced positive results from two phase I trials of V24343 for the treatment of obesity. These single and multiple ascending dose trials enrolled 16 overweight and mildly obese subjects who received treatment for 14 days. In the multiple ascending dose trial, subjects received V24343 at 4 daily dose levels of 5 mg, 15 mg, 50 mg and 100 mg. Treatment was well tolerated across the dose range, with no reported serious adverse events. The trial met multiple endpoints including improvements in weight loss, waist circumference, body fat and energy intake. After 16 days the average weight loss was 2.6 kg for V24343 (5 mg) and 5.0 kg for V24343 (100 mg) versus 0.5 kg for placebo. Based on these results, Vernalis is planning additional trials.

September 3, 2007

Obecure issued mixed results from a phase II trial of Histalean for the treatment of obesity. This double-blinded placebo-controlled study enrolled 281 subjects, with a BMI ranging from 30 to 40, in the US. The subjects were randomized into four groups to receive daily doses of Histalean (16 mg, 32 mg, or 48 mg) or placebo for 12 weeks. No statistically significant differences in weight loss were observed among any of the treatment groups compared to placebo. However, in a sub-population consisting of females, aged 50 years or less, there was a substantial difference in weight loss between the high Histalean dose group (48 mg) and placebo, showing a trend towards statistical significance (p=0.06 at 8 weeks and p=0.146 at 12 weeks). These results were even more pronounced when limited to non-hispanic women, aged 50 years and younger. At the end of week 12 this group had lost an average of 2.61 Kg (2.91%) compared to the women on placebo who lost an average of 0.4 Kg (0.43%) (p= 0.003). Based on the results Obecure plans to explore the development of Histalean in a more specific population.

August 13, 2007

MicroDose and QDose issued positive results from a phase I trial of an inhaled insulin product for the treatment of diabetes. This randomized, crossover, open-label glucose clamp study enrolled 14 healthy male subjects in the US. The trial was designed to confirm the high relative bioavailability of the QDose insulin formulation and to demonstrate the product's dose titration capability. Results showed peak levels of insulin activity were achieved more quickly following the inhaled insulin than those from the subcutaneous insulin injection. The relative bioavailability of inhaled insulin was approximately 18% during the 3 hour period following dosing. Based on the results the companies plan to advance the product into additional trials.

Phosphagenics announced positive results from a phase Ib trial of TPM-02 transdermal insulin for the treatment of diabetes. This efficacy and safety trial enrolled 45 healthy subjects at the Royal Adelaide Hospital in South Australia. Subjects received two TPM/Insulin dose formulations. Efficacy was assessed by blood glucose, endogenous insulin and C-peptide levels. The formulation safely penetrated through the skin, delivered insulin into the bloodstream over a sustained period of time and lowered blood glucose without causing adverse reactions. Based on the results, Phosphagenics plans to initiate a phase II trial before the end of the year.

July 30, 2007

Orexigen issued positive results from a phase IIb trial of Empatic for the treatment of obesity. This randomized, double-blind, placebo-controlled enrolled 620 subjects who were placed in one of six Empatic treatment arms or a placebo arm. The primary outcome was the change in total body weight at week 24 from baseline. At the highest dose tested, subjects experienced 8.6% weight loss from baseline compared to 1.1% weight loss for placebo in the intent-to-treat group, and 10.3% weight loss from baseline compared to 1.2% weight loss for placebo in the completer group (p less than .001). Adverse events were comparable between all Empatic arms and placebo. Based on the results, Orexigen plans to move forward with the development of Empatic.

April 23, 2007

Avanir announced positive results from a phase III trial of Zenvia (dextromethorphan hydrobromide/quinidine sulfate, "DMQ") for the treatment of diabetic neuropathic pain. This randomized, double-blind, placebo-controlled, parallel assignment study enrolled 379 subjects in the US and Israel. Subjects were placed into one of three treatment arms: 45 mg dextromethorphan /30 mg quinidine (DMQ 45) BID dose, 30 mg dextromethorphan / 30 mg quinidine BID dose (DMQ 30) and placebo. The primary endpoint was the score on the Pain Rating Scale based on daily journal entries. In both Zenvia treatment groups the pain ratings were lower than placebo (p less than 0.0001). Statistical significance in pain score reductions was reached with both treatment groups when compared to placebo. In the DMQ 45 group average reductions in pain score were significantly greater than placebo at days 30, 60, and 90 (p less than 0.0001 at each time point). In the DMQ 30 group statistical significance was also reached at days 30 and 60 (p less than 0.0001) and day 90 (p=0.007). The average pain relief reductions as measured on the Pain Relief Rating Scale were greater for the DMQ 45 patient group (p=0.0002) and for the DMQ 30 patient group (p=0.0083), compared with placebo. Reductions on the Pain Intensity Rating Scale reached statistical significance in the DMQ 45 group when compared to placebo (p=0.029). In addition, on the secondary endpoint of Peripheral Neuropathy Quality of Life Scale Composite score, the DMQ 45 and DMQ 30 subjects showed a greater improvement than placebo subjects (p=0.05 and p=0.08, respectively). Based on the results Avanir plans to meet with the FDA to determine the next steps toward acquiring approval for Zenvia.

Epix reported positive results from a phase Ib trial of PRX-07034 for the treatment of obesity and cognitive impairment associated conditions. This randomized, double-blind, placebo-controlled, multiple ascending dose trial enrolled 33 obese subjects who received PRX-07034 orally once-daily for 28 days. Treatment was well tolerated at doses up to 600 mg once per day. No dose limiting toxicity was identified and no serious adverse events were reported. Pharmacokinetic data was predictable, with dose proportional increases in exposures, and a half-life supporting once-daily administration. Overall results on cognitive function showed a dose-dependent trend for improvement and a dose-dependent effect was statistically significant (p=0.014 vs. placebo) at the 600 mg dose. Based on the results the company plans to move forward the development of this therapy.

July 17, 2006

Shionogi has issued positive results of a phase IIa trial of S-2367, an investigational neuropeptide Y5 antagonist for the treatment of obesity. This double-blind, two-arm study enrolled 342 obese subjects across 20 sites in the US. In the primary arm, subjects were assigned to a 4-week fixed (900-950 kcal/day) low-calorie diet (LCD), followed by randomization to one of two doses of the drug (400 mg or 1600 mg) or placebo once daily for 12 weeks, in combination with a reduced calorie diet (500 kcal/day below resting metabolic rate). In the second arm, subjects were randomized to the two drug regimens or placebo for 12 weeks without the initial LCD period. Trial data yielded significant efficacy in the primary study arm, producing a significant reduction in body weight of 2.2 kg during the treatment phase (2.5%), vs. no reduction for placebo (p<0.00001). Including the LCD phase, the high dose group lost an average of 5.3 kg (5.6%), vs. 2.5 kg (2.7%) for placebo. In the second arm, the pooled treatment groups achieved positive trending but non-significant weight loss of 3.6 kg (3.7%), vs. 2.4 kg (2.4%) for placebo (p=0.0638). Considered alone, the high-dose group did achieve significance (p=0.0479)

May 15, 2006

Vivus issued positive results of a phase II trial of Qnexa (phentermine/topiramate) for the treatment of obesity. This 4-arm, double-blind, randomized, placebo-controlled study enrolled 200 obese patients at the Duke University Medical Center; subjects received Qnexa, approved control therapy with either phentermine or topiramate alone, or placebo. Trial data indicated that treatment with Qnexa produced significantly greater weight loss than placebo or either of the two active controls through 24 weeks (25.1 lbs, vs. 4.8 lbs for placebo; p<0.0001). Further, a greater portion of subjects (more than 50% of the cohort) achieved a >10% reduction in total body weight loss than the two single agent controls combined, and no evidence of weight-loss "plateau" was noted at the end of the treatment period.

March 27, 2006

7TM Pharma announced positive results of their phase I/II trial of TM30338 for the treatment of obesity. Trial data from the first stage, an open-label escalating dose study in healthy volunteers, yielded a positive safety and tolerability profile for single doses or once- and twice-daily multiple dose subcutaneous regimens, with no serious adverse events reported and no drug-related withdrawals. No trends towards abnormal laboratory values were noted. In the trial's second stage, a double-blind crossover study, mean food intake was significantly reduced vs. placebo for both the once-daily (administered >9 hours prior to the trial meal) and twice-daily regimens.

November 14, 2005

Alizyme has announced positive results of a phase I trial of cetilistat (ATL-962) for the treatment of obesity. Safety results found no serious adverse events, and the most frequent overall adverse events (which were of mild severity) were headache (6.3%) and upper abdominal pain (5%). Incidence of these events was not dose related and did not lead to study withdrawal. Pharmacokinetic data indicated a high degree of dosing compliance throughout the trial period. Finally, preliminary drug activity was noted, with increases observed in dietary fat excretion. This randomized, double-blind, parallel-group repeat-dose study enrolled 80 otherwise-healthy obese patients (BMI:30-47) at 1US site, who received one of four doses of the drug (40 mg, 80 mg, 120 mg or 240 mg) thrice daily for 14 days.

October 24, 2005

Manhattan Pharmaceuticals announced positive results of a phase I trial of oleoyl-estrone, for the treatment of obesity. Primary safety data yielded no serious adverse events reported, no significant changes in laboratory values, and a positive overall tolerability profile. Preliminary efficacy data yielded evidence of reductions in body weight, desire to eat, hunger level, prospective food consumption, and fasting glucose and LDL levels. This two stage dose-escalation study enrolled a total of 60 obese patients: 36 were randomized 2:1 to receive one of six single doses of oleoyl-estrone (1 mg to 150 mg) or placebo, and 24 subjects received one of 4 daily doses of the drug (10 mg, 30 mg, 100 mg or 150mg) or placebo for 7 days.

September 19, 2005

Novogen has reported positive results of a phase Ib trial of their investigational drug trans NV-04, for the treatment of cardiovascular diseases related to obesity. The drug was shown to significantly improve symptoms of arterial stiffness, and to significantly lower both systolic and diastolic blood pressure. Pharmacokinetic data yielded good bioavailability, and safety data yielded no serious adverse events. This double-blind placebo-controlled cross-over study enrolled 25 overweight patients, who received the drug and placebo over two consecutive 5 week periods.

August 29, 2005

Antares Pharma reported results from a clinical trial involving Medi-Jector Vision, a needle-free injector for the deliver of insulin lispro. Results showed no significant differences in several key pharmacokinetic (PK) and pharmacodynamic (PD) measures between Medi-Jector Vision and conventional needle injection methods. The open-labeled, two-period crossover study enrolled type I & II diabetic subjects who received a controlled meal and a 10U lispro insulin dose delivered by either the Medi-Jector Vision needle-free injector or a traditional syringe injection.. Changes in insulin levels and blood glucose levels were recorded over a 4-hour period and analyzed to determine Cmax, Tmax, and AUC. The study was conducted by Dr. Sherwyn L. Schwartz at the Diabetes and Glandular Disease Clinic of San Antonio, TX.

Arena Pharmaceuticals reported a follow-up assessment of echocardiograms (ECHOs) from phase IIa trial results investigating APD356, a selective 5-HT2C serotonin receptor agonist for the treatment of obesity. The results indicated that there were no apparent drug effects on heart valves or pulmonary artery pressure after four weeks of treatment. The ECHOs were taken from patients roughly 90 days after their first APD356 dosing. The company had announced full results from the trial in May 2005. The trial demonstrated that patients taking the 15 mg dose of APD356 achieved a mean weight loss of 2.9 pounds compared with 0.7 pounds for patients taking placebo, a statistically significant (p=0.0002) difference. The company also reported completion of enrollment in its phase IIb trial with APD356 in 460 patients. Initial results are expected near the end of 2005.

June 13, 2005

Amylin Pharmaceuticals reported positive results of a phase II trial of pramlintide (AC137), for the treatment of obesity, at the European Congress on Obesity (ECO) in Athens. Results from the study met efficacy endpoints, producing statistically significant weight loss of 3.6% (3.5 kilograms), vs. placebo. The rate of weight loss in subjects receiving the study drug did not appear to plateau through 16 weeks. Weight loss was accompanied by a significant reduction in waist circumference. Patient subgroup analysis yielded evidence that pramlintide produced the highest degree of weigh loss (roughly 5%) in subjects with obesity class I (BMI: 30-35 kg/m2). This blinded, placebo-controlled study enrolled 204 obese subjects: 160 without diabetes and 44 with insulin independent Type 2 diabetes. Subjects received pramlintide or placebo three times prior to meals for 16 weeks, and all subjects were asked to maintain usual diet and exercise routines. Doses of the drug were escalated based on tolerability, with 90% of subjects reaching a thrice-daily dose of 240 mcg.

May 16, 2005

Arena Pharmaceuticals has issued positive results of a phase II trial of their 5-HT2C receptor agonist APD356, for the treatment of obesity. Results from the study yielded significant benefit in the primary efficacy endpoint, producing a mean decrease in body weight over 28 days of 2.9 pounds in the highest dose cohort, vs. 0.7 pounds for placebo (p=0.0002). Weight loss for other dose cohorts was not significant. Drug safety indications were positive, with no serious adverse events and a positive overall tolerability profile. This randomized, double- blinded, multiple-dose study enrolled 352 otherwise healthy obese subjects (SMI 30-45) across 24 US sites, who received one of 3 oral doses of APD356 (1 mg, n=75; 5 mg, n=72), or 15 mg, n=69) or placebo (n= 71) for 28 days.

December 6, 2004

Arena Pharmaceuticals has reported positive results from a phase Ib trial of APD356, their satiety-regulating selective 5HT2C agonist for the treatment of obesity. Trial results met primary safety and tolerability endpoints, with a generally mild side effects profile similar to placebo at lower doses, at the highest trial dose, subjects experienced nausea, vomiting and headache more frequently than with placebo. Furthermore, the electrocardiograms of subjects receiving the drug showed no adverse differences compared to subjects receiving placebo (cardiac consequences are a concern for several classes of serotonergic drugs). The study also further characterized the drug’s pharmacokinetic profile, noting an elimination half-life of 10 hours and achievement of steady state plasma levels within 5 days of beginning treatment. This randomized, double-blinded, placebo-controlled, multiple-dose, dose-escalation trial enrolled a total of 27 subjects, who were randomized to receive one of three doses of the drug (3 mg, 10 mg, or 20 mg daily. It was designed to evaluate the safety and pharmacokinetics of APD356 at steady-state drug levels for 14 days. Arena announced that they planned to begin dosing in a phase II trial involving 400 subjects by the year’s end.

November 15, 2004

Sanofi-Aventis has reported results from a two-year phase III study of Acomplia (rimonabant), their selective cannabinoid CB1 receptor antagonist, for the treatment of obesity. Trial data indicated that the drug’s efficacy in the treatment of obesity was sustained over a long-term administration schedule; specifically, subjects receiving high-dose Acomplia once daily for 104 weeks demonstrated significant increases in waist circumference reduction (8 cm vs. 3.8 cm; p<0.001), proportion of patients losing 5% or more of their baseline body weight (62.5% vs. 33.2%; p<0.001), proportion of patients losing 10% or more of their baseline body weight (32.8% vs. 16.4%; p<0.001), and HDL “good” cholesterol levels (24.5% vs. 13.8%; p<0.001), and a significant reduction in serum triglyceride levels (9.9% vs. 1.6%; p<0.05), compared with placebo. The improvements in HDL and triglyceride levels appear to be in part drug-induced, as they were roughly twice the level associated with those attributable to comparable weight loss. This double-blind, placebo-controlled trial randomized 3,040 obese subjects across 72 sites in the US and Canada to receive one of two once daily oral doses of Acomplia (5 mg or 20 mg) or placebo in addition to a mildly hypocaloric diet for 52 weeks, and then were re-randomized subjects to receive either 20 mg or placebo for an additional 52 weeks.

September 7, 2004

Synofi-Aventis has received positive first year results of their phase III study of rimonabant, their selective cannabinoid blocker for the treatment of obesity. Subjects receiving rimonabant for one year demonstrated significant improvement in primary and secondary symptoms of obesity, compared with placebo. Specifically, rimonabant produced significant, dose-dependant reductions in body weight, waist circumference, incidence of metabolic syndrome, and triglyceride levels, and significant improvements in insulin response and HDL “good” cholesterol scores. The double-blind, placebo-controlled trial enrolled a total of 1,507 obese subjects, who received 20 mg/day or 5 mg/day rimonabant or placebo for two years, though this data only accounts for the first.

July 5, 2004

Nastech reported positive results of their phase I c trial of PYY3-36, their intranasal-spray formulation of peptide YY 3-36, for the treatment of obesity. Trial data have indicated that administration of the drug significantly reduced caloric intake and yielded significant weight loss over the course of the study, compared to placebo. The double blind study enrolled 37 men and women between the ages of 20 and 55, with a mean BMI of 33.3 (a BMI > 30.0 is classified as medically obese). All subjects received thrice-daily intranasal sprays of placebo for two days, and then were randomized to receive placebo or 1, 2, or 3 pre-meal doses of PYY3-36 per day for 6 days. Subjects receiving the drug demonstrated significant dose-per-day-dependent reduction in caloric intake, lost an average of 1.3 pounds, and had a 6% reduction in serum cholesterol over the course of the study.

November 24, 2003

Nastech Pharmaceutical reported positive results from a phase I trial investigating PYY 3-36 (PYY), a Y2 receptor agonist for the treatment of obesity. Results showed that PYY was detected in the blood at baseline as well as after nasal administration. Most PYY was increased as early as 5 minutes after dosing and reached peak levels after around 24 minutes. PYY plasma levels were elevated 60 minutes and hunger was reduced, based on a Visual Analog Scale assessment. The nasal spray formulation was well tolerated with no nasal discomfort. The study enrolled 15 healthy subjects and was conducted at the Hammersmith Hospital in London.

April 7, 2003

Regeneron Pharmaceuticals reported negative results from a phase III trial investigating Axokine, an engineered ciliary neurotrophic factor for the treatment of obesity. Although the results achieved all endpoints compared to placebo, the overall magnitude of the weight loss was very small. Results showed that 25.1% of Axokine treated subjects lost at least 5% of their initial body weight compared with 17.6% of placebo-treated subjects. Subjects receiving Axokine achieved a greater average weight loss (6.2 lbs) than those receiving placebo (2.6 lbs). The study achieved statistically significant results in all secondary endpoints, such as proportion of subjects losing at least 10% of their initial body weight compared to placebo (11.3% vs. 4.2%). The double blind, randomized, placebo-controlled trial enrolled nearly 2,000 subjects at 65 sites across the U.S.

March 10, 2003

Metabolic Pharmaceuticals reported positive results from a phase IIa trial investigating AOD9604, a natural human growth hormone enhancer for the treatment of obesity. Results demonstrated the drug achieved weight loss trends that met expected values and occurred in predicted patterns. In the 10 mg dose group, the overall weight loss was 1.0 kg per week compared to .4 kg in the placebo group. In a subset of older subjects, the drug achieved a weight loss of .8 kg per week compared to .1 kg in the placebo group. The drug was found to be safe and well tolerated. The randomized, double blind, placebo-controlled study enrolled 36 male subjects with obesity. The trial was conducted at the Royal Adelaide Hospital in Australia.

September 3, 2002

Roche's four-year landmark study of Xenical, an FDA-approved weight-loss medication, demonstrated that the drug can prevent or delay the development of type 2 diabetes. The study, which involved 3,304 subjects, compared the effects of Xenical plus lifestyle intervention to lifestyle intervention alone. Results showed that the risk of developing type 2 diabetes was 37% lower in subjects treated with Xenical plus lifestyle intervention. In addition, weight loss was significantly greater and successfully maintained in nearly twice as many subjects in the Xenical treated group. Cardiological risk factors were also significantly improved with Xenical plus lifestyle intervention. Roche is looking to add the type 2 diabetes indication to its Xenical prescription label.

In a phase Ib trial involving 99 healthy male subjects, ATL-962 was shown to be safe and mostly well-tolerated, and demonstrated evidence of efficacy for the treatment of obesity. Subjects were given either one of several doses of ATL-962, placebo, or orlistat 120 mg three times daily for five days during which time they maintained a calorie-controlled diet. The measure of efficacy was increase in excretion of fat from the diet. 55% of subjects who received ATL-962 (50 mg - 300 mg) showed a 3-fold or greater increase in fat excretion and 27% of subjects showed a 7-fold or greater increase, compared to 44% and 11%, respectively, for the orlistat group. The most common adverse event experienced by subjects was oily stool. ATL-962, a lipase inhibitor, is being developed by Alizyme.

Positive results were found in a phase IIa clinical trial of the oral product AOD9604 for the treatment of obesity. AOD9604 was administered at three dose levels (9 mg, 27 mg, and 54 mg), and a statistically significant increase in average fat breakdown was achieved in the 27 mg group compared to placebo. Metabolic expects to initiate a safety study for a once-daily dosing before the end of 2002.

February 11, 2002

Phase IIa trial results indicate that AOD9604 is safe and well tolerated in obese subjects. The trial was designed to evaluate varying doses of intravenously administered AOD9604. Clinically obese men received treatment once a week for four weeks. In addition to the positive safety data, subjects over 35 demonstrated significant weight loss. Furthermore, an increase in fat breakdown was observed with AOD9604 compared to placebo two hours after dosing. AOD9604 is being developed by Metabolic Pharmaceuticals, a Melbourne based company.

This information does not represent a Lupus Research Institute endorsement of any listed study. It is merely a notice that the study is available. If you are presently under the care of a physician for lupus or other conditions, you should not disrupt your current program without discussing it with your doctor(s). Do not contact the Lupus Research Institute for information on these studies. Only contact the listed numbers. The Lupus Research Institute does not have any jurisdiction over or further involvement with these studies, other than to make people aware that they are being conducted.