HONG KONG – Kunshan Riboquark Pharmaceutical Technology Co. Ltd. enrolled the first patient in China for its global pivotal phase II/III study of ocular neuroprotectant candidate QPI-1007.

The study, named QRK207, is aimed at determining the effect of QPI-1007 on visual function in subjects with acute non-arteritic ischemic optic neuropathy (NAION). It is a randomized, double-masked, sham-controlled trial, in which the drug will be delivered by multidose intravitreal injections to compare its safety and efficacy to placebo, according to Riboquark.

"The trial currently contains five arms: sham treatment, low single dose, high single dose, low multiple dosing and high multiple dosing," Daniel Zurr, vice chairman of Riboquark, told BioWorld.

About 90 hospitals in several countries, including China, the U.S., Israel, Germany, Australia, Italy, Singapore and India are participating in the trial, and about 465 patients will be enrolled globally. Each patient will be treated for 12 months.

Zurr said an interim analysis is planned for January. That analysis is expected to include results from the first 200 patients (40 per arm), and one of both arms of one regimen (either single dose or multiple dosing) will be eliminated.

"The remaining arms will continue to recruit until we have 80 patients per arm. All patients will be followed up for 12 months at which time the primary endpoint will be determined," he said.

The primary endpoint is the percentage of patients who lose three or more lines in the visual acuity test.

NAION is often referred to as a "stroke in the eye." The condition can result in a significant loss of vision, and it is estimated that about 20 percent of patients with NAION experience complete vision loss in just a month or two. At the moment, there has yet to be an approved treatment for NAION.

"China has a significant NAION patient population, and we are pleased to be the first in the country to provide a siRNA-based therapy that is likely to benefit many patients in need, and to have the first patient ever dosed on a small interfering RNA trial in China," said Zicai Liang, the chairman of Riboquark.

Zurr added that the novel therapeutic could be developed for additional optic neuropathies like glaucoma, which is characterized by the death of retinal ganglion cells similar to NAION. Riboquark is initiating clinical testing of QPI-1007 in China alone in the indication of normal tension glaucoma.

Indeed, that study would mark a milestone for introducing potential siRNA therapies to China. If approved, the drug will be administered to patients through intravenous injection a few times a year by technicians in specialized eye centers in China. Riboquark holds the whole rights of QPI-1007 development and commercialization within China as well as most Asia countries.

The study in China, one of the first clinical trials of a siRNA therapy in the country, had lagged behind other sites initially due to regulatory reasons. The study had its first enrolled patient in February 2016 but has just begun in China.

"As this was the very first time that a siRNA-based drug was to be administered to Chinese patients, the Chinese FDA took its time to review the IMCT [international multicountry clinical trial] application in depth and convene an advisory board before granting regulatory approval," Zurr explained. "This detailed review process took more time than usual, but we are pleased that the outcome was positive and that we were the first to introduce this cutting-edge technology-based drug to the Chinese population."

QPI-1007 had previously been conferred orphan drug status by the U.S. FDA.

"Usually if a drug is designated orphan status in the U.S., they can apply for approval there after a single-arm, phase II/III trial," Eugene Huang, an analyst for investment firm Jefferies, told BioWorld.

Orphan drugs in the U.S. are also entitled to seven years of exclusive marketing rights and tax credits of up to 50 percent of the research and development cost. The companies developing those drugs also enjoy more assistance and faster communication with the FDA.

"Based on the strength of the results and the orphan designation in the USA, we plan to try and submit the NDA application in the USA first. Hopefully, a single phase III will be sufficient to support such submission," said Zurr.

He also said Riboquark currently is working on obtaining orphan designation in the European region. If it is successful, it plans to adopt a similar strategy for other territories.

A billion-dollar market

QPI-1007 is based on a synthetic siRNA structure that preserves activity while attenuating off-target and immunostimulatory effects. It is designed to temporarily inhibit expression of the proapoptotic protein, caspase 2.

Zurr said he has high hopes for the drug. "The NAION market alone is several hundred million USD large. Furthermore, we are working to continue to develop QPI-1007 as a neuroprotective agent in the large indication of glaucoma and that market is worth billions of USD."

"We believe that should we be able to demonstrate that QPI-1007 possesses indeed a vision-saving activity we could sell it with a premium price tag," he added.

Previously, Riboquark's parent company, Quark Pharmaceuticals Inc., had completed a phase I trial that showed QPI-1007 was safe and exhibits strong neuroprotective activity in NAION patients.

The first-in-human, open-label, single-dose, dose-escalation, safety, tolerability and pharmacokinetic study was conducted at 16 centers in the U.S. and five in Israel.

A pilot phase II double-masked, single-dose, randomized, sham-controlled study for the use of QPI-1007 in treating acute angle closure glaucoma was also completed earlier this year.

In 2014, Riboquark had raised nearly ¥45 million (US$6.8 million) in a series A financing round. The financing was led by BVCF, a leading life sciences venture capital firm in China.

In addition to BVCF, investors in the financing included SBI Incubation Co. Ltd., a subsidiary of SBI Group of Japan, the Kunshan Industrial Technology Research Institute Investment Co. Ltd. and Kunshan Hongtu Hi-tech Venture Capital Management Co. Ltd.

The proceeds were used primarily to accelerate the clinical development of QPI-1007. The capital will also be used by Riboquark to continue developing its broad pipeline of siRNA-based preclinical drug candidates for a wide range of diseases, including cancer, hepatitis and lung injury.

Riboquark also is developing a siRNA-based cosmetic product for the prevention of hair loss as a result of chemotherapy and radiation for the Chinese market.