Phase 3 Results: BLOSSOM

Lorcaserin hydrochloride, our most advanced drug candidate, is a promising oral agent being evaluated in a Phase 3 program for weight management in obese patients and in overweight patients with at least one comorbidity. BLOSSOM confirmed the results previously reported for the BLOOM trial and completed the lorcaserin Phase 3 pivotal registration program of 7,190 patients evaluated for up to two years.

In the BLOSSOM trial, lorcaserin met all primary efficacy and safety endpoints. Lorcaserin patients achieved highly significant categorical and absolute weight loss. Lorcaserin was very well tolerated and was not associated with depression or suicidal ideation. The integrated echocardiographic data set from BLOSSOM and BLOOM rules out a risk of valvulopathy in lorcaserin patients according to criteria requested by the FDA. Treatment with lorcaserin also resulted in significant improvements as compared to placebo in multiple secondary endpoints associated with cardiovascular risk.

Efficacy

Measurements of efficacy using ITT-LOCF analysis showed that lorcaserin met all primary endpoints. Patients treated with 10 mg of lorcaserin dosed twice daily achieved highly statistically significant categorical and average weight loss after 12 months:

• 47.2% of patients lost at least 5% of their body weight, compared to 25.0% for placebo. This result satisfies the efficacy benchmark in the most recent FDA draft guidance which provides that a weight-management product can be considered effective if the proportion of patients who lose at least 5% of baseline body weight in the active-product group is at least 35%, is approximately double the proportion in the placebo-treated group, and the difference between groups is statistically significant.
• 22.6% of patients lost at least 10% of their body weight, compared to 9.7% for placebo.
• Patients achieved an average weight loss of 5.9%, compared to 2.8% for placebo.

Patients treated with 10 mg of lorcaserin dosed twice daily who completed the 52-week trial according to protocol demonstrated the benefit of long-term treatment with lorcaserin:

• 63.2% of patients lost at least 5% of their body weight, compared to 34.9% for placebo.
• 35.1% of patients lost at least 10% of their body weight, compared to 16.1% for placebo.
• Patients lost an average of 17.0 pounds, or 7.9%, of their body weight, compared to 8.7 pounds, or 3.9%, for placebo.
• The quartile of lorcaserin patients with the greatest weight loss lost an average of 35.1 pounds, or 16.3%, of their body weight. These patients lost 36% more body weight than the top quartile of placebo patients.

Safety and Tolerability Profile

Lorcaserin was very well tolerated. The most frequent adverse events and their rates for patients who took lorcaserin twice daily or placebo, respectively, were as follows: headache (15.6% vs. 9.2%), upper respiratory infection (12.7% vs. 12.6%), and nasopharyngitis (12.5% vs. 12.0%).

Adverse events of depression, anxiety and suicidal ideation were infrequent and were reported at a similar rate in each treatment group.

Cardiovascular Safety

The integrated BLOOM and BLOSSOM echocardiography data set rules out a risk of valvulopathy in lorcaserin patients according to criteria requested by the FDA. Echocardiographic evaluations showed no association between lorcaserin and the development of heart valve insufficiency. Rates of new FDA-defined valvulopathy in BLOSSOM at Week 52 were as follows: lorcaserin 10 mg twice daily (2.0%), 10 mg once daily (1.4%) and placebo (2.0%).

Secondary Endpoints

Treatment with lorcaserin over one year was associated with significant improvements or strongly favorable trends compared to placebo in multiple secondary endpoints, including blood pressure and lipids.

Patient Disposition

BLOSSOM evaluated 4,008 patients with an average body mass index of 35.9 and baseline weight of 220 pounds. The Week 52 completion rate was higher for patients on lorcaserin 10 mg twice daily (57.2%) and 10 mg once daily (59.0%) compared to patients on placebo (52.0%). Discontinuations for adverse events were low and as follows: lorcaserin 10 mg twice daily (7.2%), 10 mg once daily (6.2%) and placebo (4.6%).

BLOSSOM Confirms BLOOM

In BLOSSOM, as in BLOOM, lorcaserin’s excellent tolerability allowed patients to begin treatment at the full dose immediately, without a titration period, and achieve rapid weight loss. As in BLOOM, significant weight loss compared to placebo was shown at the first trial visit, two weeks following randomization.

The efficacy for the BLOOM and BLOSSOM trials after one year of treatment are summarized in the table below.

	BLOOM		BLOSSOM
	10 mg BID*	Placebo	10 mg BID*	10 mg QD*	Placebo
>5% weight loss (Per protocol)	66.4%	32.1%	63.2%	53.1%	34.9%
>5% weight loss (ITT-LOCF)	47.5%	20.3%	47.2%	40.2%	25.0%
>10% weight loss (Per protocol)	36.2%	13.6%	35.1%	26.3%	16.1%
>10% weight loss (ITT-LOCF)	22.6%	7.7%	22.6%	17.4%	9.7%
Mean weight loss (Per protocol)	8.2%	3.4%	7.9%	6.5%	3.9%
Mean weight loss (ITT-LOCF)	5.8%	2.2%	5.9%	4.8%	2.8%

   * p<0.0001 compared to placebo

BLOSSOM Trial Design

BLOSSOM is a double-blind, randomized, placebo-controlled trial that enrolled 4,008 patients in approximately 100 sites in the US. The trial evaluated 10 mg of lorcaserin dosed once or twice daily versus placebo over a one-year treatment period in obese patients (BMI 30 to 45) with or without co-morbid conditions and overweight patients (BMI 27 to less than 30) with at least one co-morbid condition. The trial did not include dose titration or a run-in period. Patients were randomized at baseline in a 2:2:1 ratio to lorcaserin 10 mg twice daily, placebo or lorcaserin 10 mg once daily. Patients received echocardiograms at baseline, month 6 and at the end of the trial to assess heart valve function over time. In contrast to the BLOOM trial, there were no echocardiographic exclusion criteria for entry into BLOSSOM and there was no oversight or interim data review monitoring by an independent safety monitoring board.

(This page was last updated: January 5th, 2010. Additional information regarding Arena is available in its SEC filings.)

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