The API and tablets of the DPP-4 inhibitor: HD118 in development by Huadong Medicine have recently obtained the Drug Clinical Trial Approval, which is a Chinese Class 1 new drug of DPP-4 inhibitor type. Thus far, another new player has joined the Class 1 new drugs of DPP-4 inhibitor type, to march into the hypoglycemic drug market in China.

Overview of DPP-4 inhibitors

DPP-4 inhibitor drugs account for about 26% of the global hypoglycemic drug market, which are the hypoglycemic drug with the second highest proportion following insulin, wherein, the sitagliptin of MSD is the world’s first marketed DPP-4 inhibitor, followed by other similar products that have been marketed including vildagliptin, saxagliptin, linagliptin, and alogliptin, etc.

Sitagliptin has been accounting for the largest market share among the DPP-4 inhibitor drugs. According to the statistics of the PDB database, the market size of global DPP-4 inhibitors and compound preparations thereof exceeded USD 12 billion in 2016, wherein, the market size of sitagliptin reached USD 6.4 billion.

The current market size of the diabetes pharmaceutical products is about RMB 40 billion in China, wherein, the market size of the oral hypoglycemic drugs is about RMB 24 billion, involving many big varieties reaching RMB 1 billion level. All the new drugs of DPP-4 inhibitor type in the above table have been marketed in China, and all the single preparations of those drugs have been included in the 2017 new-edition national medical insurance catalog of China, and restricted as second-line drug.

Chinese enterprises also have conducted multi-aspect layout in the registration application of Class 1 new drugs of DPP-4 inhibitor type. See the following table for the clinical trial projects of which the status was displayed as "in progress" on the Drug Clinical Trial Registration and Information Publicity Platform in China by January 10, 2018.

Sweet sorrow

The Class 1 new drug HD118 of Huadong Medicine approved for clinical trial this time was originally developed by the U.S. Phenomix Corporation, and Sino-US Huadong Pharmaceutical obtained all relevant technologies and Chinese patent rights of this new drug in development in China for the treatment of diseases within category of type 2 diabetes through technology transfer contract in 2014.

 Earlier, HD118 has been completed the relevant clinical trial overseas. According to a 12-week, multicenter, double-blind, controlled clinical trial in which 423 diabetes patients participated, HD118 had good hypoglycemic effects, and did not show serious and high-incidence adverse reactions in terms of safety.

According to information, the compound patent of this drug will expire in 2027 in China, and according to the optimistic forecast of an insider, HD118 is expected to be approved and marketed in China in 2020, meaning that HD118 will have a 7-year patent protection period after being marketed in China.

However, the value of the future quasi-7-year patent protection period of this Class 1 new drug in development seems to be not high, as seen from the current situation.

The current market of new drugs of DPP-4 inhibitor type in China has already been carved up by the imported original drugs that have entered China early, and the Chinese pharmaceutical enterprises are still at the stage seeking a foundational breakthrough; moreover, transnational pharmaceutical enterprises which have the first mover advantages have been conducting the next round of R&D for product updating and upgrading in the fierce DPP-4 inhibitor competition pattern of multiple parties in the world, such as the development of the new variety of long-acting or even ultra-long-acting DPP-4 inhibitor. By comparison of strength, the gap between both sides is evident.

Looking around the pharmaceutical enterprises in China, in the armament race of Class 1 new drugs of DPP-4 inhibitor type, a trial of Retagliptin Phosphate Tablets of Hengrui Medicine with registration No. of CTR20160943 is doing the Phase III clinical subject recruiting, and has a significant time advantage among the multiple applicants in China. This drug in development is expected to become the first Chinese-produced Class 1 new drug of DPP-4 inhibitor type that receives approval.

How will be the latecomers’ chance to win the competition on such a market already crowded with similar marketed products?

Will the Achilles’ Heel become the potential breakthrough?

DPP-4 inhibitors have undoubtedly become one of the most-watched segments in the global diabetes drug field in recent years. DPP-4 inhibitors, the variety with the largest market share among the oral hypoglycemic drugs, have undergone substantial growth in recent years.

However, it’s worth mentioning that DPP-4 inhibitors have been warned by FDA for many times due to problems in terms of safety: FDA warned that DPP-4 inhibitors potentially cause severe joint pain in 2015; FDA required labels of alogliptin and saxagliptin pharmaceutical products to be added with the safety warning content of "potential increased risk of heart failure" in 2016. Such safety problems seem to have become the Achilles’ Heel of new drugs of DPP-4 inhibitor type.

The good news is that those problems currently fall into the "potential" scope, and sufficient reliable clinical data are required to support whether they exist or not.

Opportunities seem to emerge under the crisis—in my opinion, proving this "Achilles’ Heel" to be false, namely, clinically proving the safety advantage of own varieties will enable the new drugs of DPP-4 inhibitor type to be more favored by the market, because the clinical treatment advantages are fundamental to drugs after all.

This might be a chance for the Chinese pharmaceutical enterprises to win.