Aslan fails to roar as lead drug flunks phase 2 trial

Aslan Pharmaceuticals has been hit by the news that its lead drug varlitinib missed the mark in a gastric cancer trial, sending its shares down almost 16%.

The Singapore biotech says its phase 2 study of varlitinib as a first-line therapy for patients with HER1/HER2 co-expressing advanced or metastatic gastric cancer showed that the drug provided no additional benefit when added to standard chemotherapy when it came to shrinking tumors.

Patients treated with varlitinib plus a regimen called mFOLFOX6 had an average tumor shrinkage of 22% after 12 weeks, compared to 12.5% for patients treated with mFOLFOX6 with placebo, which wasn’t statistically significant improvement.

Aslan is continuing to develop the small-molecule HER1, HER2 and HER4-targeting drug in other cancers, including biliary tract cancer where it is a phase 3 program, but the failure has dented confidence in its drug just a few months after the biotech made its U.S. listing debut on the Nasdaq.

The biotech’s chief operating officer, Mark McHale, Ph.D., said the setback was disappointing but stressed that this type of stomach cancer is challenging to treat, particularly as most patients already have advanced disease when they are diagnosed.

“We are encouraged by the positive safety data and remain confident that varlitinib’s potent pan-HER inhibition has the potential to yield benefits in biliary tract cancer where HER family expression is known to be high,” he added.

The company—led by former AstraZeneca exec Carl Firth—can take some comfort from a trend in favor of Aslan’s drug on progression-free survival in the gastric cancer trial, as well as other secondary endpoints including ECOG performance status, which measures patients’ ability to carry out daily activities. The proportion of patients with the best performance status (ECOG 0) was 46% with varlitinib and 19% with placebo.

The next important readout for the program will come very soon—at the ASCO gastrointestinal cancers symposium that starts later this week—where Aslan is due to report data from a phase 1b first-line biliary tract cancer study.

Most significant, however, will be the results due in the second half of this year from its pivotal TreeTopp trial in second-line biliary cancer, which represents its earliest chance for a regulatory filing for varlitinib.

The gastric cancer trial is not the first setback for varlitinib, however. In 2017, it failed a phase 2 trial in breast cancer, and last year Aslan said it would have to amend an ongoing Chinese study of the drug in biliary tract cancer because enrollees had more severe disease than expected based on historical controls, leading to a weaker than expected response to treatment.

At the time, analysts at Edison said it wasn’t a big problem, because although the trial would be delayed the company could still file for approval in China based on the TreeTopp results.

Aslan focuses on cancers that are rare in the U.S. and Europe, which can make enrolling patients into trials difficult. It says its presence in Asia gives it an advantage “in diseases where either the cancers are more prevalent, or the availability of suitable patients is greater” and helps the company overcome those recruitment obstacles.

Its other clinical candidates including DHODH inhibitor ASLAN003—a potentially first-in-class therapy in midstage trials for acute myeloid leukemia—and Bristol-Myers Squibb-partnered RON/cMET inhibitor ASLAN002, an immuno-oncology candidate. Outside oncology, it also has an IL-4/IL-13 inhibitor, ASLAN004, in a phase 1 trial in atopic dermatitis.