Today, the Committee for Medicinal Products for Human Use (CHMP) recommended Novo Nordisk’s Ozempic (semaglutide) for EMA approval. FDA approved the once-weekly GLP-1 agonist earlier this month, and based on this CHMP endorsement, final marketing authorization for Europe is anticipated in 1Q18.
As part of EU approval, Novo Nordisk has agreed to conduct post-market studies investigating the long-term impact of semaglutide on retinopathy. This requirement for approval is a reaction to the heightened retinopathy risk seen in SUSTAIN 6 (HR=1.76, 95% CI: 1.11-2.78), a pre-market CVOT for semaglutide, and indeed, FDA convened an Advisory Committee to discuss this safety signal prior to making a regulatory decision for the US. A post-hoc analysis of SUSTAIN 6 suggested that retinopathy may have occurred at a higher rate in the semaglutide arm of the trial due to “early worsening phenomenon,” when dramatic A1c reductions lead to a transient increase in eye events. A longer-term study could lend additional support to this early worsening hypothesis, providing reassurance on the safety of semaglutide for patients/HCPs.
The US label for Ozempic (section 5.3) contains a retinopathy warning similar to those on insulin products (which also cause steep A1c decline/transient early worsening), suggesting careful monitoring for people with pre-existing eye disease (another known risk factor).
Novo Nordisk’s announcement further highlights that the European label for Ozempic could include data on (i) superior weight loss vs. comparators and on (ii) improved renal outcomes – neither of which made it onto the US label. Our sense is that FDA is more conservative in including results in product information (e.g. EMA included LEADER data on the Saxenda label, and it seems highly unlikely that this would pass FDA’s desk), which is disappointing when semaglutide’s weight loss benefit has been incredibly compelling throughout the SUSTAIN program. The agent is even being investigated for obesity.
-- by Payal Marathe and Kelly Close