TransThera's resistant biliary cancer drug cleared in China

China's regulatory authority has approved TransThera Sciences' multikinase inhibitor Yochanra as the world's first drug to overcome resistance to FGFR inhibitors in bile duct cancer.

The National Medical Products Administration (NMPA) has cleared Yochanra (tinengotinib) for adult patients with unresectable advanced or metastatic bile duct cancer – also known as cholangiocarcinoma (CCA) – who have been previously treated with FGFR inhibitors and developed FGFR2 resistance mutations.

CCA is a rare but aggressive disease that usually develops and progresses silently, meaning most people are diagnosed at a late stage when treatment options are limited, and it kills three-quarters of patients within a year of diagnosis. Symptoms can include jaundice, abdominal pain, weight loss, pale stools, and itching, but are often mistaken for less serious conditions.

TransThera's drug – which is also being developed in the US and Europe – is the first therapy in China specifically approved for use in this CCA setting, according to the Nanjing-based company.

It has been approved on the strength of the open-label, phase 2 FIRST-08 trial conducted in 50 Chinese patients, which revealed a 28% objective response rate (ORR) – all partial responses – with a median duration of response of 8.5 months. Disease control, i.e. when the tumour either did not grow or shrank, came in at 82%, according to data reported at this year's ASCO cancer congress.

Although its overall incidence in China is low, CCA is relatively common in certain regions of the country, including Shanghai and Quidong, due to relatively high rates of chronic hepatitis B virus (HBV) infection, parasitic infections, and rising rates of metabolic disorders like diabetes and obesity.

Around a quarter of patients with CCA harbour FGFR2 mutations, making them candidates for FGFR inhibitors like Incyte's pemigatinib, approved in China in 2022 and sold by Innovent, which is marketed in other markets as Pemazyre.

In a statement on the approval of Yochanra – which targets FGFR1/2/3, JAK1/2, VEGFR2, and Aurora A/B kinases – TransThera said that it will address a global market estimated to be worth $2 billion in 2024 and predicted to grow to $3.2 billion next year.

The company said that various companies have attempted to develop drugs that can overcome FGFR2 resistance, without success. It is running a confirmatory phase 3 trial of the drug in China, as well as an international phase 3 trial intended to support filings in other regions, including Europe and the US.

Yochanra has been granted orphan drug and fast-track designations by the FDA as a treatment for biliary tract cancer, as well as orphan drug status by the EMA. TransThera is also exploring the potential of the drug in other solid tumours, including prostate, breast, and liver cancer.