EU clears AZ's SERD camizestrant, as FDA review drags on

The EU has delivered some good news to AstraZeneca's oncology business, approving its oral selective oestrogen receptor degrader (SERD) for breast cancer, even as it faces obstacles on its path to market in the US.

The European Commission has cleared camizestrant, as Etcamah, for use in combination with a CDK4/6 inhibitor as a first-line treatment for locally advanced or metastatic HR-positive, HER2-negative breast cancer with a mutation in the ESR1 gene.

It can be used in patients who develop an ESR1 mutation, without disease progression, during standard first-line endocrine therapy, such as an aromatase inhibitor in combination with a CDK 4/6 inhibitor.

Camizestrant has already been approved in some other markets, including Japan, UAE, and Saudi Arabia, but its progress in the important US market looks less certain.

In April, the FDA's Oncologic Drugs Advisory Committee (ODAC) voted that data from the pivotal SERENA-6 trial was not strong enough to support approval, and the US regulator subsequently extended its review by three months to look at additional data. Specifically, it is looking at data on ESR1 mutations in circulating tumour DNA (ctDNA), specifically how well ctDNA clearance data aligns with efficacy outcomes.

The ODAC vote was viewed as a major setback in AZ's plan to grow camizestrant into a $5 billion-a-year drug, part of a portfolio of 20 new medicines it hopes will catapult sales above the $80 billion threshold by the end of the decade, so the EU approval is a boost to the company.

AZ recently presented updated results from SERENA-6, showing that its drug reduced the risk of disease progression or death by 55% compared to the control treatment of anastrozole or letrozole and a CDK4/6 inhibitor, with a 37% improvement in the time to second disease progression and a trend towards improved overall survival.

Etcamah becomes the first next-generation drug in the oral SERD class to be approved for frontline use in this type of breast cancer in Europe, according to AZ, which also said it can be used with all EU-approved CDK4/6 inhibitors, namely Pfizer's Ibrance (palbociclib), Novartis' Kisqali (ribociclib), and Eli Lilly's Verzenios (abemaciclib).

Around one in three patients with this form of advanced breast cancer have tumours that develop ESR1 mutations before disease progression.

AZ's head of oncology and haematology, Dave Fredrickson, said the EU approval "marks an important shift in the first-line treatment paradigm" for this type of breast cancer and provides "a new standard-of-care to address emerging resistance ahead of disease progression."

There are two approved drugs in the oral SERD class, Menarini/Stemline's Orserdu (elacestrant) and Eli Lilly's Inluriyo (imlunestrant), which are both approved for second-line use in patients with ESR1-mutated, HR-positive, HER2-negative advanced breast cancer.