Invokana

Drug Overview

Invokana (canagliflozin; Johnson & Johnson/Mitsubishi Tanabe/Daiichi Sankyo) is a member of the novel sodium-glucose cotransporter-2 (SGLT-2) inhibitor class. SGLT-2 inhibitors do not target insulin secretion or sensitivity and do not interfere with glucose metabolism. They prevent filtered glucose from being reabsorbed in the kidney rather than actively facilitating glucose filtration and excretion. Due to this distinct mechanism of action, when SGLT-2 inhibitors are used as monotherapy they do not lower glucose to unsafe levels and thus avoid the risk of hypoglycemia.

Analyst Outlook

Topline results from an interim analysis of Invokana’s (canagliflozin; Johnson & Johnson/Mitsubishi Tanabe/Daiichi Sankyo) pivotal diabetic nephropathy (DN) trial indicated that it met its primary endpoint, which confirms suggestions of a renal benefit seen in its CANVAS cardiovascular outcomes trials (CVOTs). The latter also led to a CV indication in the US and inclusion of the CV data in its European label. However, it will be important to see details from the DN trial, such as whether it confirms an increase in amputations seen in the CANVAS program. This led to label warnings and was likely behind Invokana’s substantial decline in revenues in 2017. If there is a suggestion of the risk in the DN trial, revenues will likely decrease substantially further, even with the DN indication. Datamonitor Healthcare has concerns that could be the case, since nothing was mentioned about the issue or safety in the topline results. However, our base case assumes there was no increased risk, but that physicians will still be concerned about it, leading Invokana to underperform competing sodium-glucose cotransporter-2 (SGLT-2) inhibitors, which have not shown such an issue in their own CVOTs. It will also be important to see if there was a good benefit on CV death in Invokana’s DN trial, because in the CANVAS trials, the reduction was not as pronounced as seen for Jardiance (empagliflozin; Boehringer Ingelheim/Eli Lilly) in its own CVOT. Hence, there is some uncertainty whether the difference is due to the risk of the particular patients enrolled or whether Jardiance has a true advantage in this regard. If Invokana does not show a good benefit on CV death, while the reason may be uncertain, physicians may prefer Jardiance, in case it does have a larger effect, though reimbursement is a major determinant of which agents are used.