HONG KONG – Beigene Ltd. is advancing its small-molecule Bruton's tyrosine kinase (BTK) inhibitor BGB-3111 into two more global clinical trials, further exploring the efficacy of the drug candidate in treating B-cell cancers.

One of the additional trials is a phase III study of the oral inhibitor candidate of BTK in previously untreated patients with chronic lymphocytic leukemia (CLL), a type of blood cancer that affects the development of white blood cells.

The study compares BGB-3111 with bendamustine and rituximab, and will be conducted in North America, Europe, Australia, New Zealand and Asia.

"The clinical trial is testing the drug used as first-line therapy for CLL and we aim to examine whether BGB-3111 could be an effective treatment option for a broad population of CLL patients," Lucy Li, Beigene's director of strategy and investor relations told BioWorld.

The other newly added trial is BGB-3111's phase II study in combination with obinutuzumab in patients with relapsed follicular lymphoma, the most common of the slow-growing non-Hodgkin's lymphomas.

The study is designed to evaluate BGB-3111 in combination with obinutuzumab in patients who have had at least two prior lines of therapy and progressed within 12 months of their last treatment.

"There has not been an approved BTK inhibitor targeting follicular lymphoma on the market and we are pretty advanced in this indication," said Li.

Li said the ultimate goal for both clinical trails is drug registration, so the Beijing-based company would later commercialize BGB-3111 in the global market.

"The initiation of two additional pivotal trials expands our global registration-directed clinical development of BGB-3111 to additional indications, including patients with follicular lymphoma, a common B cell malignancy for which BTK inhibitors are not yet approved," said John Oyler, founder, CEO and chairman of Beigene.

The Chinese immuno-oncology drug developer launched a global phase III trial for patients with Waldenström's macroglobulinemia, another type of non-Hodgkin lymphoma in February.

Janssen jumps ahead with Imbruvica

Li said the company is not disclosing any detail regarding the trials' timeline yet.

Beigene's BGB-3111 was expected to be the first China-discovered and developed BTK inhibitor obtaining a market approval in the country. However, while Beigene is still waiting for results, a competitor already started selling its BTK inhibitor drug in China this month.

In August, Imbruvica capsules, co-developed by Xian Janssen Pharmaceutical Co. and Pharmacyclics LLC, an Abbvie Inc. subsidiary, got the marketing approval from the China Food and Drug Administration as a monotherapy for adult patients with CLL, including small lymphocytic lymphoma, and for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Shortly after the approval came through, Janssen officially launched the drug in the China market on Nov 12.

Also headquartered in Beijing, Xian Janssen is one of the Janssen pharmaceutical companies under global pharmaceutical giant Johnson & Johnson.

"Clinical data demonstrate clearly that compared to existing treatment options, ibrutinib can help prolong life, and it is also well tolerated," said Li Bin, head of medical affairs at Xian Janssen during the launching event. "Furthermore, ibrutinib is convenient to take orally once a day, which is significant in terms of quality of life."

Currently, Imbruvica is available in 49 cities in China, and as of the end of August 2017, it has been approved in 86 countries and has been used to treat more than 90,000 patients according to Xian Janssen.

Beigene is catching up with its competitors as Li said that the enrollment for the phase II trial of BGB-3111 in China in MCL patients completed in September and the company will submit the results to the Chinese authority for approval once they complete the data analysis.

"We plan to apply through the CFDA's priority review system and our drug should not be that slow in terms of gaining the approval in China," said Li. "Plus we are more confident in terms of the selectivity and efficiency of BGB-3111.

Li said BGB-3111 is designed to be more selective to avoid off-target toxicities. For example, BGB-3111 has a better target inhibition not only in the blood but also in relevant tissues for epidermal growth factor receptor (EGFR). If EGFR gets hit, patients could suffer from gastrointestinal toxicity and severe bleeding.

Experts in China are calling for new treatment options for CLL and MCL that are both becoming more prevalent in the country. Particularly most patients who relapse or develop resistance to therapy do not have alternative options as there is no new medication coming out.