Pfizer, Arvinas join SERD club with Veppanu approval

Pfizer and Arvinas are poised to bring the third oral selective oestrogen receptor degrader (SERD) to market in the US, after the FDA cleared vepdegestrant for a form of breast cancer.

Vepdegestrant has been approved under the Veppanu brand name as a second-line or later therapy for HR-positive, HER2-negative advanced breast cancer patients whose tumours have mutations in the ESR1 gene.

On launch, Veppanu will join Menarini/Stemline's Orserdu (elacestrant) and Eli Lilly's Inluriyo (imlunestrant), which were approved for second-line treatment of HR+, HER- advanced breast cancer with ESR1 mutations in January 2023 and September 2025, respectively.

Arvinas said that its drug is the first heterobifunctional protein degrader or PROTAC (proteolysis-targeting chimaera) to be approved by the FDA, an inflection point for a platform technology that the company has been working on for more than a decade.

A fourth oral SERD from Roche (giredestrant) has now also been submitted for approval in the US for a similar second-line indication, with a decision due by 18th December. However, another from AstraZeneca (camizestrant) hit an obstacle last week when an FDA advisory committee voted against the drug's use in a first-line setting.

Commercial prospects for Veppanu are hard to call, given that it is participating in what looks to be quite a crowded category with a clinical profile that looks to be similar to its rivals. And while Pfizer has partnered the drug since 2021, it decided last September that it would not be deploying its marketing muscle for the product, and the two companies are currently looking for a third-party to commercialise it.

The two partners had intended to be "launch-ready" by the FDA's action date for Veppanu's review, which wasn't until 5th June, and said they "remain on track" to have a third party in place

Based on the pivotal VERITAC-2 trial, Arvinas had hoped to go for approval of the drug in an all-comer HR-positive, HER2-negative advanced breast cancer – including patients without ESR1 mutations – which would have given it a competitive edge. However, the FDA made it clear it was not minded to accept that broader label, and that was one of the reasons Pfizer decided to rein back its involvement.

In a statement, Arvinas said the green light for Veppanu is a "transformative event" for the company as its first product approval and demonstrates the clinical impact of its PROTAC approach.

"It also strengthens our confidence in the breadth and versatility of our exciting clinical pipeline across oncology, neurodegenerative, and neuromuscular diseases," said chief executive Randy Teel.

Arvinas' pipeline also includes PROTAC-based candidates targeting KRAS G12D, BCL6, and HPK1 for various forms of cancer, an LRRK2-directed drug for Parkinson's disease, and a polyQ-AR degrader for spinal-bulbar muscular atrophy (SMBA).

Teel said earlier this year that while Veppanu is a "potentially best-in-class therapeutic option" for this type of breast cancer, the best way for Arvinas to build shareholder value is to focus on its other programmes.