Novartis goes 0 for 2 in PD-1 blockade

The failure of Novartis’s spartalizumab in 2020 prompted that in-house anti-PD-1 MAb to be quietly shelved in favour of tislelizumab, a rival anti-PD-1 the Swiss group licensed from BeiGene the following year for $650m. Now that second deal is toast, too.

BeiGene today trumpeted the regaining of full rights to tisle as an exciting strengthening of its portfolio – and well it might, given the cash Novartis had sunk into the project. While Novartis pulling the plug is understandable given the drug’s protracted delays in the west, for the Swiss firm this is another black mark against its disaster-prone oncology portfolio.

Last year Novartis swung the axe over oncology, discontinuing a number of early-stage clinical projects, and saying its top priority for Car-T, for instance, was immunology rather than blood cancers. Formally the group’s oncology division was taken back into its pharmaceuticals business, favouring instead a split along geographical (US/ex-US) lines.

First approval

Ironically, though it was becoming increasingly clear that tislelizumab was finding the going tough beyond China, with liver and lung cancer US filings abandoned, for instance, the ending of the BeiGene deal came just as it got its first western approval.

Today tislelizumab was greenlit in the EU as Tevimbra for second-line oesophageal squamous cell carcinoma, BeiGene said. In the US a first-line filing in this cancer type has been accepted by the FDA, which has set a second-half 2024 PDUFA date, while a second-line application has endured several delays, with approval now expected "in 2023".

The PD-1 drug is actually the second BeiGene project Novartis has given up on this year. In July a US SEC filing quietly disclosed that the Swiss company was walking away from ociperlimab, an anti-TIGIT MAb it had optioned from BeiGene two years earlier for $300m up front.

Though BeiGene might rue the loss of a big pharma partner, it can at least count the financial benefit of having done a deal. And this isn’t the first time tisle has delivered: an earlier deal with Celgene was terminated in 2019 after that group’s takeout by Bristol Myers Squibb, bringing a $263m up-front, $150m equity investment plus $150m break fee.

Investors might now be wondering where Novartis's future lies in oncology. Before the BeiGene deal terminations and early-stage pipeline purge came the notorious failure of the STING agonist MIW815, which Novartis had licensed from Aduro in 2015, handing over $225m on the eve of that company’s Nasdaq IPO; the technology was backed only by preclinical data. And canakinumab's last cancer trial, Canopy-A, failed last year,

If Novartis is now easing back from immuno-oncology then perhaps it will have better luck in radiopharmaceuticals. Here too, however, there have been setbacks, as launches of Lutathera and Pluvicto were accompanied by production problems; Pluvicto spent much of 2023 on the US short supply list, and Novartis has apparently yet to meet demand.

Selected Novartis setbacks in oncology

Source: OncologyPipeline.