AstraZeneca gets first okay for CTLA4 drug tremelimumab

West Chester - Circa November 2020: AstraZeneca plant. AstraZeneca has been working on a vaccine for the Coronavirus, COVID and COVID-19.

AstraZeneca's lengthy and turbulent development of CTLA4 inhibitor tremelimumab has at least led to a regulatory approval as part of a combination therapy for advanced liver cancer.

Tremelimumab has been approved by the FDA in the US for use in tandem with AZ's PD-L1 inhibitor Imfinzi (durvalumab) to treat adults with unresectable hepatocellular carcinoma (HCC), the most common tumour type affecting the liver.

The CTLA4 inhibitor – now given the brand name Imjudo – is only the second drug in the class to be approved after Bristol-Myers Squibb's well-established Yervoy (ipilimumab), which is used alongside BMS' PD-1 inhibitor Opdivo (nivolumab) in several solid tumours, including HCC and lung, colorectal, skin, and kidney cancers.

The FDA approval covers a single 300 mg dose of Imjudo given alongside 1,500 mg Imfinzi, followed by Imfinzi every four weeks – known as the STRIDE (single tremelimumab regular interval durvalumab) regimen – in previously untreated HCC patients.

That takes CTLA4 inhibition into uncharted territory in HCC, as BMS' Yervoy plus Opdivo is FDA-approved only as a second-line treatment after sorafenib, sold by Bayer as Nexavar and also available as a generic.

AZ sees the first-line HCC indication as a big opportunity for its immuno-oncology franchise, so much so that it used a priority review voucher – typically worth around $100 million – to reduce the FDA review time for the application to six months.

In the HIMALAYA trial, patients treated with the STRIDE regimen saw a 22% reduction in the risk of death versus Nexavar, and almost one in three patients (31%) were still alive at three years compared to 20% of the control group.

The study bucked the trend of tremelimumab adding little or nothing when added to Imfinzi across a range of cancer types, whilst adding to the side-effect burden of therapy. Yervoy is also acknowledged to be hard to tolerate.

"In the past, patients living with liver cancer had few treatment options and faced poor prognoses," said Andrea Wilson Woods, president and founder of liver cancer charity Blue Faery. "With today's approval, we are grateful and optimistic for new, innovative, therapeutic options," she added.

One rival to Imjudo/Imfinzi in previously untreated HCC is Roche's dual regimen of PD-L1 inhibitor Tecentriq (atezolizumab) and CD20-targeting antibody Avastin (bevacizumab), which was approved by the FDA in 2020 based on the results of the IMbrave150 study.

Liver cancer is the third-leading cause of cancer death and the sixth most commonly diagnosed cancer worldwide. It is the fastest-rising cause of cancer-related deaths in the US, with approximately 36,000 new diagnoses each year.

Imjudo plus Imfinzi has also been filed for approval in Europe, Japan, and several other countries, said AZ in a statement.