FDA delays verdict on AZ breast cancer drug

After its advisory committee voted against AstraZeneca's camizestrant as a treatment for breast cancer in April, the FDA has extended its review of the filing to look at additional data.

The extra time will be needed to review additional data for the oral selective oestrogen receptor degrader (SERD), which has been filed as a frontline treatment of adults with locally advanced or metastatic HR-positive, HER2-negative breast cancer with a mutation in the ESR1 gene.

The delay to the FDA's decision-making could be a positive for AZ, allowing the company to build the case for camizestrant following a six-to-three vote by the Oncologic Drugs Advisory Committee (ODAC) that it had failed to show conclusively that switching from patients' current therapy to camizestrant in combination with a CDK4/6 inhibitor provided a clinically meaningful benefit.

The case for that approach was made in the SERENA-6 trial, which was reported at last year's ASCO congress and found that the switch reduced the risk of disease progression or death by 56%.

In a statement, AZ said that it has "provided additional analyses requested by the FDA in support of the application," including data on ESR1 mutations in circulating tumour DNA (ctDNA) that will be presented at this year's ASCO, which starts on Friday. Specifically, the FDA asked to see "ctDNA clearance data linked to longer-term efficacy outcomes," it added.

The ODAV vote has been viewed as a major setback in AZ's plan to grow camizestrant into a $5 billion-a-year drug, part of a portfolio of new medicines it hopes will drive sales above the $80 billion threshold by the end of the decade.

Since the negative ODAC vote, camizestrant has been recommended in the EU by the EMA's human medicines committee, the CHMP, which should set up an approval within the next few weeks. The drug has already been approved in the United Arab Emirates and Saudi Arabia for this indication.

There are two approved drugs in the oral SERD class in the US, Menarini/Stemline's Orserdu (elacestrant) and Eli Lilly's Inluriyo (imlunestrant), which are both approved for second-line use in patients with this form of breast cancer, giving AZ an opportunity to leapfrog them into the frontline setting.

A bigger opportunity could come if the results are positive in the ongoing SERENA-4 trial in an all-comer HR-positive breast cancer population, with and without ESR1 mutations, which is likely to be crucial for AZ as it tries to position the SERD as a backbone first-line treatment option for the disease.

Results from SERENA-4 are due later this year, while additional studies in post-surgery treatment of earlier-stage breast cancer could provide additional growth opportunities.

"We are committed to continuously advancing the clinical landscape in oncology in pursuit of improving outcomes for patients," said Susan Galbraith, AZ's head of oncology and haematology R&D.

"The SERENA-6 treatment strategy epitomises this approach by monitoring patients for the emergence of ESR1 mutations in ctDNA and testing if a switch of endocrine backbone therapy at this point improves outcomes," she added.

"We look forward to continuing the dialogue with the FDA in order to bring the benefits of camizestrant with this innovative treatment strategy to eligible patients in the US as quickly as possible."

There is no word from AZ on the length of the extension – although it is generally three months – or when a decision may be expected.

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