HONG KONG – Japan’s Seikagaku Corp. is contemplating the next move for its ONO-5704/SI-613 (diclofenac etalhyaluronate), a treatment for arthritis that it is co-developing with fellow Japanese company Ono Pharmaceutical Co. Ltd. The two partners presented positive results from a phase III study testing the drug on patients with knee osteoarthritis at the 93rd annual meeting of the Japanese Orthopaedic Association on June 11.

A total of 440 Japanese patients took part in the randomized, double-blind, placebo-controlled, parallel-group comparative study of two groups of 220 between April 2017 and January 2019. The two groups were injected with 3 ml of either ONO-5704/SI-613 or placebo in the knee joint cavity six times every four weeks, and were evaluated by their WOMAC B, or stiffness, and WOMAC C, or physical function, scores.

The patients, ages 40 to 75, were diagnosed with knee osteoarthritis according to criteria set by the American College of Rheumatology, had Kellgren-Lawrence radiographic scores between grade 2 or 3, and had suffered pain from osteoarthritis for a year or longer.

The companies reported that the group receiving ONO-5704/SI-613 demonstrated a “statistically significant difference” in the primary endpoint, defined as the mean change in the WOMAC pain score, or knee pain evaluation index, compared to the group receiving the placebo 12 weeks after initial administration. The ONO-5704/SI-613 group also demonstrated a “statistically significant difference” in the study’s secondary endpoint, the WOMAC B and C scores, 12 weeks after initial administration.

Seikagaku’s shares (Tokyo:4548) jumped to ¥1,183 (US$11.0238) on June 11 while Ono Pharmaceutical shares (Tokyo:4528) hit ¥3,133 (US$29.1949) on the same date. On June 16, Seikagaku shares gained 5.06% to close at ¥1,162, while Ono shares gained 3.36% to close at ¥3,103.

A Seikagaku source told BioWorld that the results were “favorable” and in line with company expectations. The two companies are currently conducting a clinical study testing SI-613 against enthesopathy, have completed analysis of the results of a phase IIb study and are contemplating the next steps.

Meanwhile, Ono’s head of corporate communications, Yukio Tani, told BioWorld that “the results of the phase III clinical study in patients with osteoarthritis of knee, hip and ankle joints were within our expectations, while we have not got the results we expected in patients with osteoarthritis of elbow and shoulder joints.”

ONO-5704/SI-613 is designed to work by chemically binding hyaluronic acid and diclofenac, an anti-inflammatory drug, using Seikagaku’s technology, offering relief to patients with osteoarthritis pain and inflammation. The drug is injected directly into the joint cavity, thus minimizing systemic exposure to the diclofenac and potentially lowering the risk of a systemic adverse drug reaction.

In January, the two companies submitted a Japanese NDA for ONO-5704/SI-613’s manufacturing and marketing approval to treat osteoarthritis of the knee, joint, hip joint and ankle joint, which is currently under review.

The application included the results of three phase III studies; a phase II confirmatory study in knee osteoarthritis patients, a phase III study in patients with osteoarthritis in the shoulder, elbow, hip and ankle joints, and a phase III long-term study in patients with osteoarthritis in the knee, shoulder, elbow, hip and ankle joints.

The partners are also looking to take the drug overseas. The Seikagaku source said the firms are in the process of selecting a partner for a potential phase III study in the U.S., after completing the  analysis of results from a phase II knee osteoarthritis study in that country.

Seikagaku also inked an agreement in with Eisai Co. Ltd. in April to co-develop and market SI-613 in China, with the two companies to jointly develop the drug to treat knee osteoarthritis. Seikagaku raked in an up-front payment, as well as development and sales milestone payments, from the alliance.

The Seikagaku pipeline also includes SI-6603, a treatment for lumbar disc herniation for which an additional phase III study is currently underway in the U.S.; SI-614 to treat dry eye, for which phase II/III studies are currently underway in the U.S.; SI-449 to treat interstitial cystitis and bladder pain syndrome, for which phase I/II studies are currently underway in the U.S.; and SI-449, a medical device to treat adhesion barrier, for which a pivotal study in Japan is currently underway.

Ono also announced that Opdivo (nivolumab), which the company launched in Japan in September 2014, received FDA approval to treat patients with advanced, recurrent or metastatic esophageal squamous cell carcinoma after prior fluoropyrimidine- and platinum-based chemotherapy. Developer Bristol Myers Squibb Co. received the approval on June 11.

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