Pfizer kills off MacroGenics-partnered solid tumor bispecific

Pfizer's pipeline clear out also affected three dermatology drugs. (Pfizer)

Pfizer has dumped a bispecific antibody developed through its collaboration with MacroGenics. The solid tumor drug was the first partner-developed program based on MacroGenics' bispecific platform to enter the clinic, but it has fallen before clearing phase 1.

In 2010, MacroGenics granted Pfizer the rights to candidates based on its bispecific antibody platform against two cancer targets. Pfizer began testing the lead drug from the collaboration, PF-06671008, in humans in 2016. At that time, Pfizer planned to enrol 110 solid tumor patients in the dose-escalation study and assess the number of dose-limiting toxicities and objective responses.

Early in 2018, Pfizer ramped up its enrollment target to 152 subjects but the study never got close to that goal. Before 2018 was over, Pfizer had halted enrollment at 28 subjects. Pfizer terminated the study altogether earlier this year.

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Now, Pfizer has confirmed the demise of PF-06671008, which targets P-cadherin and CD3. The design of the drug was underpinned by evidence that P-cadherin is elevated in multiple types of solid tumor and associated with poor survival. That evidence also attracted Novartis, which tested a P-cadherin inhibitor in humans a few years ago, but is yet to translate into the hoped-for therapeutic progress.

Pfizer cleared PF-06671008 from its clinical pipeline in an update that also saw the removal of two other oncology drugs. PF-05212384, a pan-PI3K/mTOR inhibitor that entered the clinic a decade ago, reached the end of the road, as did OX40 receptor agonist PF-04518600. 

The pipeline clear out also affected three dermatology drugs, including phase 2 TYK2/JAK1 inhibitor PF-06700841. Pfizer sees the breadth of its pipeline of kinase inhibitors as a strength, as compared to rivals such as AbbVie and Gilead that are developing single assets in many indications. But efforts to take oral PF-06700841, also known as brepocitinib, forward in psoriasis have hit a wall in phase 2.

Pfizer is continuing to study a topical formulation of PF-06700841 in psoriasis and is running studies of the oral formulation in other indications, including psoriatic arthritis, Crohn’s disease and vitiligo.

The other dermatology drugs affected by the pipeline clear out are psoriasis prospect PF-06763809 and atopic dermatitis biologic candidate PF-06817024. Pfizer’s decision to drop PF-06817024 comes shortly after it presented late-phase data suggesting its oral molecule abrocitinib can rival Sanofi and Regeneron’s Dupixent for the atopic dermatitis market.

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