EC Approves Extended Invokana Indication On Renal Outcomes In DKD
First SGLT2 Inhibitor In Europe To Gain Extended Indication
Executive Summary
Mundipharma has announced the European Commission’s extension of the indications for Invokana to include renal outcomes data from the Phase III CREDENCE study.
Janssen Pharmaceutical Cos./Mundipharma International Corp. Ltd.’s SGLT2 inhibitor, Invokana (canagliflozin), has become the first drug in nearly 20 years to have its indications in Europe extended to include renal outcomes data from a Phase III study in patients with diabetic kidney disease (DKD) and type 2 diabetes.
The European Commission’s approval, announced by Mundipharma on 1 July, follows a positive recommendation from the EMA’s CHMP in May 2020 to include renal outcomes data from the Phase III CREDENCE study in Invokana’s indications in the EU. The change is likely to drive Invokana’s uptake in what is a significant therapeutic segment, at least until similar indication updates are potentially gained by other sodium glucose co-transporter-2 (SGLT2) inhibitors.
Canagliflozin is the first therapy, since the approval of ACE-inhibitors and angiotensin II receptor blockers (ARBs) nearly 20 years ago, to slow the progression of DKD in type 2 diabetes, points out Mundipharma, the global network of private companies which is Janssen’s commercial partner for canagliflozin. Mundipharma has exclusive distribution rights for canagliflozin in various European countries. Patients in whom canagliflozin is recommended include diabetics with moderate to severe renal impairment and albuminuria (urinary albumin:creatinine ratio >300mg/g).
Datamonitor Healthcare analysts expect Invokana’s lead to only be temporary, as other SGLT-2 inhibitors, including AstraZeneca PLC’s Forxiga (dapagliflozin) and Boehringer Ingelheim International GmbH/Eli Lilly & Co.’s Jardiance (empagliflozin), are also being evaluated in late-stage studies for renal disease, and for non-diabetic chronic kidney disease. The Phase III study of dapagliflozin in chronic kidney disease was stopped early in March 2020 due to overwhelming efficacy, on the recommendation of its independent data monitoring committee. (Also see "Farxiga CKD Trial Stopped Early For Efficacy, Giving The SGLT2 Inhibitor An Edge" - Scrip, 30 Mar, 2020.)
Mundipharma estimates that around 40% of patients with type 2 diabetes will eventually develop kidney disease, or around 21 million patients.
The CREDENCE study in 4,401 subjects with DKD and type 2 diabetes treated with maximum doses of an ACE-inhibitor or ARB showed that canagliflozin was associated with a 30% reduction in a composite endpoint comprising end-stage renal disease, doubling of serum creatinine and renal or cardiovascular death, compared with placebo.
The study was stopped early in July 2018, owing to positive efficacy findings, and the US Food and Drug Administration approved a new indication for Invokana in September 2019, to reduce the risk of end-stage kidney disease, worsening of kidney function, cardiovascular death, and hospitalization for heart failure in adults with type 2 diabetes and diabetic kidney disease (nephropathy) with a certain amount of protein in the urine.
The use of SGLT-2 inhibitors in diabetic nephropathy patients in the US is expected to grow by 80% or more over the next eight years, according to Datamonitor analysts, with the value of the diabetic nephropathy market in the US, Japan and the top-5 EU marketed expected to reach $1.6bn in 2026.