Pharma giant Pfizer and Arvinas’s human epidermal growth factor receptor 2 (HER2) negative breast cancer therapy, vepdegestrant, has seen mixed results after it was only able to extend progression-free survival (PFS) in certain patients in a Phase III trial.
Topline results from the company’s Veritac-2 trial (NCT05654623) showed a clinically meaningful improvement in PFS in patients with oestrogen receptor 1-mutant (ESR1m) breast cancer. However, the company said that it was not able to improve PFS in the intent-to-treat (ITT) population.
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The global randomised study enrolled 624 patients at sites in 26 countries who had previously received treatment with cyclin-dependent kinase (CDK) 4/6 inhibitors alongside endocrine therapy. The trial pitted vepdegestrant against AstraZeneca’s Faslodex (fulvestrant).
Data on overall survival (OS), a key secondary endpoint, was not yet mature with less than a quarter of the required number of events having occurred.
Pfizer describes vepdegestrant as a potential first-in-class investigational oral proteolysis targeting chimera (PROTAC) oestrogen receptor degrader. Developed as part of a $2.4bn partnership between Pfizer and Arvinas, the oral drug was designed for a natural protein disposal system to specifically target and degrade oestrogen receptors.
Following the announcement of the mixed results, Arvinas’ stock price dropped more than 51% from $17.70 per share down to $8.59 at the time of publication (11 March 10am EST).
Arvinas president John Houston said: “The first Phase III data readout for a PROTAC degrader represents a significant achievement and these data show that vepdegestrant has the potential to provide clinically meaningful outcomes for thousands of patients with metastatic breast cancer whose tumours harbour oestrogen receptor 1 mutations.”
It follows after the US Food and Drug Administration (FDA) granted fast track designation for the investigation of vepdegestrant as a monotherapy. Research by GlobalData estimates that by the end of next year, the breast cancer therapy could bring in as much as $75m for the two companies, with that figure expected to rise to $841m by the end of 2030. The World Health Organization (WHO) found that breast cancer caused 670,000 deaths globally in 2022.
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Pfizer oncology chief development officer Megan O’Meara said: “Patients with advanced ER+/HER2- metastatic breast cancer face significant clinical challenges, with limited treatment options following disease progression and the development of resistance to available endocrine therapies.
“This data from the Veritac-2 trial supports the potential of vepdegestrant to give patients whose tumours harbour ESR1 mutations additional time without disease progression, compared to Faslodex.”
Elsewhere in the field of HER2 breast cancer, NiKang Therapeutics has concluded the first cohort dosing in the open-label Phase I trial of NKT3964. Meanwhile, Phoenix Molecular Designs has started dosing in the Phase II arm of a trial examining its metastatic breast cancer candidate, PMD-026.
