SHANGHAI – Taiwan Liposome Co. (TLC) is hoping to give patients with osteoarthritis of the knee a better option for pain management with TLC599, a steroid API wrapped in a sustained release liposome delivery package. The company released positive top-line results from phase I/II data for a trial in Taiwan and Australia, and kicked off a phase II trial in both places with plans underway for China and the U.S.

The phase I/II trial was conducted in 40 patients in Taiwan and Australia with TLC599 demonstrating safety in injected doses of 6 mg and 12 mg. It showed a sustained, clinically meaningful decrease in pain from baseline to week 12, according to several pain assessments.

The randomized, open-label, single-dose study found no significant adverse events over the 12-week period following injection.

"The results of this trial demonstrate that TLC599 may address the critical issue of short duration of action that limits the therapeutic potential of corticosteroid treatments in wide use today," said George Yeh, president of Taipei-based TLC.

Yeh will present full data on Wednesday during the emerging markets track of the J.P. Morgan Healthcare Conference in San Francisco.

The sustained-release capability of TLC599, to last up to 12-weeks, is critical to the drug's future success. It was designed to address a gap in the current standard of care that can leave patients in pain for several weeks between treatments.

Patients with osteoarthritis of the knee often start with oral pain medications but when these no longer work they may be prescribed cortisone injections which can last only one or two weeks.

Because these injections worsen joint damage over time, physicians will only prescribe three or four injections a year. If the arthritis worsens, then the next step is for patients to undergo knee replacement surgery.

As the aging population in China and the U.S. increases, so do the number of people suffering from osteoarthritis of the knee. A longitudinal study of 17,128 Chinese people found that 8.1 percent had symptomatic osteoarthritis of the knee, with an estimated prevalence of 110 million people in China overall. IMS projects that by the year 2030, there will be 23.5 million people suffering from knee osteoarthritis in the U.S. TLC599 is currently in the clinic in Taiwan and Australia, but the company is also looking to target the more sizable U.S. and China markets.

TLC599's liposome reformulation, based on TLC's Bioseizer technology, can be likened to an onion, delivering the drug just as each layer of the onion is peeled back. By prolonging the delivery of the drug, in this case the marketed steroid dexamethasone, the lipid reformulation can reduce the frequency of drug administration.

In addition, the company has used a water soluble steroid, along with the sustained-release delivery, that may have the additional benefit of reducing the toxicity and joint damage that occurs with other steroid treatments. In the phase I/II study, no toxicity was found, Yeh said, and they are looking to their phase II study to provide further data. The phase II trial will test for placebo effect, an important factor when seeking market approval for pain medications.

AN ASIA FIRST REGULATORY STRATEGY

China has made it easier for reformulated steroids with clear clinical efficacy to move up the drug classification ladder; where they were once considered class 5, with class 6 reserved for generics, drug developers can now apply to have reformulated candidates considered as class 2 drugs, and benefit from an accelerated review timeline.

TLC's prudent regulatory plan for its reformulated steroid involves seeking approval in Asia first with the U.S. following after. Since the U.S. requires two pivotal studies, Yeh said the plan "is to be approved in Asia first and then use that as one of the pivotal studies for the U.S."

He predicted that more companies will take advantage of China's new rules regarding reformulated drugs. "With the new categories and a focus on reformulated drugs that demonstrates clinical efficacy or improvement, you will see more companies make applications for reformulated drugs at a much earlier stage, and put China as part of the NDA process," said Yeh.

However, the CFDA is still sluggish to respond to applications for drugs that are considered generics with data from Taiwan. TLC's Proflow for peripheral arterial disease, approved in Taiwan and licensed to Sciclone Pharmaceuticals Inc., of Foster City, Calif., for commercialization in China, still has not received the greenlight from the CFDA. Proflow's main benefit is to double the product's shelf life. (See BioWorld Today, July 2, 2013.)

TLC has a pipeline of candidates reformulated for targeted delivery and/or sustained release in several therapeutic areas: oncology, to broaden a drug's use in other indications; peripheral arterial disease, to extend product shelf life; ophthalmology, to reduce infection and discomfort; arthritis, to reduce joint pain and; as an anesthetic, to minimize the need for postsurgical painkillers.