Pfizer downgrades disitamab again

Pfizer’s disitamab vedotin hasn’t looked like a priority for a while, and the company disclosed on Tuesday that it had downgraded expectations again for this Seagen-derived HER2-targeting ADC. Pfizer wrote off $1.6bn in relation to the asset in 2025, it disclosed in its fourth-quarter earnings.

The write-off is to account for the “diminishing valuation” of disita-V in this indication, something the group blamed on strong readouts and higher sales expectations for its approved bladder cancer product Padcev. But development of disita-V is still ongoing, a Pfizer spokesperson told ApexOnco.

Meanwhile, the company also disclosed several trial discontinuations in its latest pipeline update. The most high-profile is the phase 3 Her2Climb-02 study of its HER2 inhibitor Tukysa, another Seagen-derived asset, in second-line breast cancer.

Keynote-D74

Disita-V was originated by China’s RemeGen, and in 2021 it was licensed by Seagen, which was then acquired by Pfizer in 2023 for $43bn.

As such, disita-V would have been ascribed a value at the time of the deal, with this being carried on Pfizer's balance sheet; it’s this that is now being chipped away. Pfizer also wrote off $200m in relation to disita-V last year, citing competition; AstraZeneca and Daiichi's Enhertu seemed like the obvious contender at the time.

The sole Pfizer-sponsored phase 3 trial of disita-V is Keynote-D74, in first-line HER2-expressing bladder cancer.

In RemeGen's hands disita-V holds the distinction of being the first China-originated ADC to secure approval there, for third-line HER2-positive gastric cancer, trademarked Aidexi. The asset is also in various Chinese phase 3s, and Pfizer has mid-stage studies ongoing in breast cancer and solid tumours.

Tukysa climbdown

Elsewhere, the HER2 inhibitor Tukysa is still struggling to remain relevant. The discontinued trial, Her2Climb-02 trial, tested a Kadcyla combo in second-line HER2-positive breast cancer. The study yielded a PFS benefit versus Kadcyla alone in December 2023, but last November a publication in the Annals of Oncology revealed that the trial had failed on OS, with a hazard ratio of 1.23.

Pfizer might have higher hopes for the Her2climb-05 trial, testing Tukysa plus Roche’s Herceptin and Perjeta as first-line maintenance: last year the group reported a PFS benefit versus Herceptin plus Perjeta, although OS data are immature. Pfizer has said it plans to discuss the results with regulators, but it doesn’t appear to have filed the project yet.

The group also wrote off $820m in relation to Tukysa in 2025. The drug was approved in 2020, alongside Herceptin and chemo for HER2-positive breast cancer patients who had previously received an anti-HER2-based regimen. But sales shrank 4% in 2025, to $463m, against a backdrop of growing Enhertu dominance.

Pfizer’s other two oncology discontinuations involved its Arvinas-partnered oral oestrogen degrader vepdegestrant in neoadjuvant breast cancer, and a combination of the KAT6 inhibitor prifetrastat plus the CDK4 inhibitor atirmociclib in metastatic breast cancer.

The former move isn’t surprising, given that Pfizer and Arvinas are looking for a new partner for vepdegestrant.

As for prifetrastat, the KAT6 inhibitor last year went into phase 3, in combination with Faslodex in second-line breast cancer, and various other combos are being tested in phase 1.

Other recent Pfizer discontinuations, not spelled out in the latest update, have involved its anti-mesothelin ADC PF-08052666, a pan-KRAS inhibitor, PF-07985045, and a PD-L1-targeting conjugate, PF-08046037.

Pfizer oncology discontinuations & deprioritisations in Q4 2025

Source: company Q4 2025 presentation.