Aslan turns focus to biliary tract cancer as lead drug flops in PhII gastric cancer study

About a year after securing the full rights to develop and commercialize varlitinib from Array BioPharma $ARRY, Aslan Pharma $ALSN said the drug failed to confer a statistically significant reduction in tumors of patients with gastric cancer in a mid-stage study.

Carl Firth

The Singapore-based company — which is run by former BD chief for AstraZeneca Carl Firth and went public in an underwhelming IPO last May — has essentially abandoned testing the experimental drug in patients with gastric cancer and will concentrate on studies in biliary tract cancer and other indications, it said on Monday.

Originally developed by Array, the drug is also known as ASLAN001 and is an oral, small molecule that inhibits the activity of epidermal growth factor receptors HER1, HER2 and HER4 — which are mutated or overexpressed in many tumors and typically cause uncontrolled growth. Its mechanism of action is similar to that of Roche’s cancer drug Herceptin, which targets HER2.

In the study, varlitinib was being tested as a first-line treatment in patients with gastric cancer in addition to a standard chemotherapy regimen. After 12 weeks of treatment, patients given the drug + chemotherapy experienced an average tumor shrinkage of 22%, while those on chemotherapy alone saw their tumors shrink by 12.5% — however that difference was not deemed statistically significant. Aslan’s shares were down 24% before the bell.

In terms of safety, 73.1% of patients on the experimental drug regimen experienced a grade 3 or higher adverse event, versus 88.5% of patients on chemotherapy alone, Aslan said.

According to clinicaltrials.gov, about 50 patients were enrolled in the study, which, if positive, was designed to evolve into a Phase III trial evaluating the drug in hundreds of patients.

Other than diet, tobacco use, gender (male) and age (60-80), gastric or stomach cancer is also linked to infection with H. pylori bacteria. Over time it can lead to precancerous changes to the inner lining of the stomach, according to the American Cancer Society (ACS), which estimates the number of new cases of stomach cancer have decreased about 1.5% each year over the last decade in the United States, although in the late 1930s, stomach cancer was the leading cause of cancer death in the region. In other parts of the world, stomach cancer is much more common, particularly in less developed countries, the ACS added.

Mark McHale

“First-line gastric cancer is a very challenging indication to treat and the majority of patients present with advanced disease at initial diagnosis,” Aslan’s COO Mark McHale said in a statement. “To date, no targeted therapies have been approved to treat gastric cancer with low HER-family expression. Whilst we are disappointed by the study findings, 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.”

Data from a first-line biliary tract cancer study will be presented at a medical conference later this week, while top-line data from a pivotal study in second-line biliary tract cancer are expected in the second half of 2019, the company said.

“While the varlitinib clinical data generated to date…have demonstrated some activity, we continue to want to see more clinical and mechanistic validation for varlitinib given that biliary tract cancer has historically been a difficult space for drug development and the mechanistic advantages of varlitinib being a pan-HER inhibitor remain unclear, given the implications of targeting HER4 remain poorly understood. Overall, while we’re positive on Aslan’s Asia focused development strategy and the experience of the management team, we want to see more clinical and mechanistic validation for varlitinib in a catalyst-rich 2019,” Leerink analysts wrote in a note.

In 2017, Aslan reported that varlitinib induced a statistically significant reduction in tumor size in patients with breast cancer in a Phase II trial, but the drug did not confer any improvements in progression-free survival or overall survival.

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