Saxenda (liraglutide): NDA 206321

The Office of Clinical Pharmacology (DCP-2 and DPM) has reviewed the clinical pharmacology data submitted on 12/2013 under NDA 206321 and recommend approval from a clinical pharmacology perspective.

Supportive of this effect, in trial 3970 (obstructive sleep apnea), polysomnography demonstrated that liraglutide 3 mg attenuated the noctural decline in heart rate observed in the placebo group.

In contrast, if the results exclude an increased risk of MACE >=30% (i.e., upper bound of the 95% CI for the HR of liraglutide vs. placebo is <1.3), it will then be a subject of review whether there is any suggestion that the overall result may not apply to patients treated with Saxenda.

Taken together, I agree with Dr. Golden (as well as the members of the 11 September 2014 EMDAC) that the clinical trials with Saxenda provided substantial evidence of clinically meaningful efficacy with respect to its effect on body weight.

Fasting body weight decreased 5.7% with liraglutide and 1.6% with placebo (reported p <0.0001).

When considering liraglutide- and placebo-treated patients who lost 10% of their body weights, the proportions were 34% and 15%, respectively, for the large trial, and 23% and 7%, respectively, for the trial in patients with type 2 diabetes.

The sponsor conducted the phase 2 dose-ranging trial 1807 to establish the doseresponse relationship of four doses of liraglutide and placebo on weight loss.

A medullary thyroid carcinoma registry-based case series of at least 15 years duration to systematically monitor the annual incidence of medullary thyroid carcinoma in the United States and to identify any increase related to the introduction of Saxenda (liraglutide [rDNA origin] injection) into the marketplace.

• Revise Warnings and Precautions Section 5.2 Acute Pancreatitis for consistency with the class.

See Dr. Amarylis Vega's REMS review for more details.

Liraglutide has also been shown to increase heart rate in humans and cause c-cell tumors in rodents.5 The relationship of liraglutide to pancreatitis or pancreatic or thyroid tumors (including non-c-cell tumors) in humans has been speculated, but remains controversial.8,9,10,11,12 This review focuses on liraglutide clinical trial data for weight loss efficacy as well as for human safety.

The majority of the adverse events (AEs) confirmed by the EAC as acute pancreatitis in the liraglutide group were serious and / or severe, whereas the event in the placebo-treated group was not reported as serious or severe.

In addition, the one AE reported as acute pancreatitis in trial 1807 (not adjudicated) in a patient treated with liraglutide 3 mg, was reported as serious and severe.

He has no recommendations for postmarketing commitments, agreements, or risk management steps.

This section will review the data submitted from the 1839 trial; i.e., PMR 2802-8.