A Glimpse of the Situation of SGLT-2 Inhibitors, the Up-rising Star of Oral Hypoglycemic Drugs, in China

The market size of the global hypoglycemic drugs exceeded USD 40 billion in 2017, which became the second largest drug market next only to the oncology drug market. From the distribution of the top 15 varieties by sales on the hypoglycemic drug market, we can see the current product pattern: insulin accounts for more than half of the shares, followed by DPP-4 inhibitors, GLP-1 analogues, and SGLT-2 inhibitors

Structure of use of hypoglycemic drugs inside and outside China

According to PDB data, the sales of diabetes drugs in sample hospitals of China were RMB 5.76 billion in 2017, wherein, the oral hypoglycemic drugs accounted for 56%, with the top 3 varieties by sales of oral hypoglycemic drugs being acarbose, metformin, and glimepiride.

The oral hypoglycemic drugs in China are mainly those three drugs, while on the overseas mature markets, besides those three drugs, the DPP-4 and SGLT-2 inhibitors that are used the most have preliminarily completed substitution of the early varieties, showing that the drug use structure of hypoglycemic drugs in China is significantly different from that of overseas mature markets; in terms of the hypoglycemic drugs for injection, China is based on recombinant human insulin, compared to the GLP-1 analogues, insulin analogues, and the new-generation ultra-long-acting insulin, etc. that rapidly grow in overseas clinical application.

Up-rising star: SGLT-2 inhibitors accounting for one third of the global market

On the global oral hypoglycemic drug market, DPP-4 inhibitors are one of the main drugs, with market share second only to that of metformin. Compared to DPP-4 inhibitors, the up-rising star SGLT-2 inhibitors have the same hypoglycemic effect, and more importantly, the unique cardiovascular benefits and weight losing advantage of SGLT-2 inhibitors enable such drugs to be quite favored by the drug regulators and clinical trials in recent years.

In particular, reducing cardiovascular risk has become one of FDA’s important standards for review of hypoglycemic drugs in recent years, and the therapeutic advantages of SGLT-2 inhibitors have been meeting the clinical demands for hypoglycemic drugs that can also reduce cardiovascular risks. SGLT-2 inhibitors are forecasted by Evaluate Pharma to surpass DPP-4 inhibitors to become the top oral hypoglycemic drugs in 2022.

The world’s first SGLT-2 inhibitor was approved for marketing in 2012. Global sales of such oral hypoglycemic drugs reached USD 2.632 billion in 2017, growing by 7.7% year on year, accounting for 6.5% of the diabetes drug market. SGLT-2 inhibitor market is mainly divided by canagliflozin, dapagliflozin, and empagliflozin, from the perspective of the sales.

SGLT-2 inhibitors provide good compliance as oral hypoglycemic drug, and its cardiovascular benefits have also been recognized besides the hypoglycemic effect. Empagliflozin was the world’s first oral hypoglycemic drug that showed the cardiovascular benefits in the clinical trial. In December 2016, FDA approved empagliflozin to be used to reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and cardiovascular disease based on the results of a postmarket clinical trial.

Overview of the competition preparations for SGLT-2 inhibitors in China

All the above three SGLT-2 inhibitors have been approved for marketing in China by September 2017. The patent application of canagliflozin on the Chinese market has encountered a setback: in addition to the rejection, the crystal form patent originally with protection period until 2027 was ruled to be invalid in 2015.

Such situation of canagliflozin on the Chinese market creates the room for the development of the Chinese generic drug enterprises. According to incomplete statistics, the number of manufacturers of canagliflozin generic drugs has reached 27 in China, wherein, the canagliflozin tablets of Jiangsu Hansoh Pharmaceutical is the rapidest in the progress: it has been applied for production in February 2018. There are also numerous manufacturers of generic drugs of the other two main SGLT-2 inhibitors, besides the canagliflozin tablets.

In the new drug development queue of similar drugs, there have been 3 products in development that are in clinical trials, wherein, Hengrui Medicine’s Henagliflozin proline is the fastest in the progress, with the Phase III clinical trial with registration No.: CTR20170527 started in June 2017 and now in the "underway, having not recruited" stage, and Hengrui has completed clinical trials of other 4 registration numbers, with clinical trials of 12 registration numbers underway; Xuanzhu Pharma’s  Janagliflozin and HEC Pharma’s Rongliflozin L-Pyroglutamic Acid are at Phase I clinical trials; Allist Pharmaceuticals’ Empagliflozin and Tianjin Institute of Pharmaceutical Research’s Tianagliflozin have been approved for clinical trials.