HONG KONG – China's Zhejiang Hisun Pharmaceutical Co. Ltd. said results of two key phase III trials for HS-25, a cholesterol absorption inhibitor that targets hyperlipoproteinemia, showed both met the standard 12-week descent rate of low-density lipoprotein cholesterol (LDL-C), while adverse drug reactions were minor. In the next one to two months, the company is expected to apply to the National Medical Products Administration (NMPA), China's FDA, for marketing clearance.
One trial was a multicenter, randomized, double-blinded, placebo-controlled design testing HS-25 for treating primary hyperlipoproteinemia. A total of 374 participants entered the trial, with an LDL-C descent rate fall of between 14.6 and 16 percent. The safety of short-term and long-term use was shown to be positive.
The second study was an open-label and long-term phase III trial of HS-25 combined with atorvastatin treatment, targeting hypercholesterolemia patients with atherosclerotic cardiovascular disease. A total of 255 patients participated in that trial. With a foundation of a 10-mg atorvastatin treatment, the use of HS-25 resulted in a fall in LDL-C rate of 16.4 percent. The rates of adverse drug reaction on HS-25 and atorvastatin were 7.9 percent and 13.6 percent, respectively.
Despite the positive news, Hisun's shares fell 10 percent to ¥10.44 (US$1.523) on Sept. 14. But the stock closed at ¥11.85 (US$1.728) on Sept. 20.
HS-25 is expected to encounter intense competition in China, as the drug watchdog has allowed more than 30 pharmaceutical companies to produce generic versions of Zetia (ezetimibe), HS-25's main rival.
Both products can be used to lower the injection of statin drugs, reducing the risks of rhabdomyolysis, which can cause severe muscle pain, liver damage, kidney failure and even death.
Produced by Merck & Co. (NYSE:MRK), Zetia targets the same indications and was launched in China in 2006. As HS-25's effect in lowering the rate of LDL-C is similar to that of Zetia, its competitiveness remains in question as the trial results showed no relative advantage over Zetia, which had 2017 global sales of $3.49 billion, $10 million of that coming from China.
The market for high-end chemical hypolipidemic agents in China's public medical institutions in 2017 was around ¥226 million (US$33 million), and the top 20 drugs account for nearly 90 percent market share. Statin drugs are the major product, representing around 87.6 percent of the market.
Hisun submitted its application to Zhejiang province medical authorities in October 2013 to conduct clinical trials, and it has invested ¥225 million (US$32.8 million) on HS-25 so far.
"Our company will proactively move the project forward," a Hisun spokesperson told BioWorld.
Also in the pipeline
Shortly after unveiling the HS-25 data, Hisun revealed that the NMPA has acknowledged the receipt of the marketing application for its Humira (adalimumab, Abbvie Inc.) biosimilar, which targets ankylosing spondylitis, rheumatoid arthritis (RA) and plaque psoriasis.
According to the company's half-year financial report, AD-35, its oral tablet formula of a neuroprotectant that targets Alzheimer's disease, has started phase IIa trial in the U.S. after completing phase I in August last year. Hisun's photosensitizer, HPPH, which is intended to treat later-stage esophageal cancer, is currently undergoing an efficacy trial.
Hisun's glargine insulin and insulin aspart are in phase III testing, while the company is accepting participants for an efficacy and pharmacokinetics trial for 20(S)-ginsenoside C-K in RA patients.
In terms of generic drugs, the company claimed that its irbesartan, used mainly for treating hypertension, is the first in the country to have passed the quality and efficacy consistency evaluation. Its rosuvastatin calcium tablet, targeting high cholesterol and cardiovascular disease, is the third in China to have passed the evaluation.
In August 2017, Hisun partnered with the Infectious Disease Research Institute, a nonprofit global health organization, to develop the inhalable CPZEN-45, a tuberculosis drug candidate, amid the growing issue of antibiotic-resistant TB.
Hisun did not answer BioWorld's inquiry on updates of its pipeline candidates.
Founded in 1956, the company listed on the Shanghai Stock Exchange in 2000. It has claimed that its research spending amounts to 10 percent to 12 percent of total sales.