ASCO: Sanofi says early amcenestrant data could see it be 'endocrine backbone therapy' in breast cancer

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(Sanofi)

A new early peek at data from Sanofi’s breast cancer hopeful amcenestrant has encouraged the French Big Pharma to see it placed firmly at the front of future treatment pathways.

In pooled data from the phase 1 AMEERA-1 trial, made up of 35 patients, its drug amcenestrant, an oral selective estrogen receptor degrader (SERD), hit an objective response rate (ORR) of 34% and a clinical benefit rate (CBR) of 74% when combined with Pfizer’s approved breast cancer med Ibrance (palbociclib), which works as an CDK4/6 inhibitor.

The data come from a series of post-menopausal women with ER+/HER2- metastatic breast cancer (MBC) who were pretreated with endocrine therapy in the advanced setting for at least six months or had resistance to adjuvant endocrine therapy.

It’s difficult to glean too much from the abstract, dropped Wednesday evening ahead of the American Society of Clinical Oncology meeting proper next month, as it is just a preliminary analysis from the open-label AMEERA-1 study, but Sanofi still saw enough to be optimistic about its future.

Breaking it down, amcenestrant was looked at across several dose-escalation cohorts (Part C) at 200 mg (made up of nine patients) and 400 mg (made up of six patients) daily and in a dose expansion cohort (Part D, with 30 patients) at 200 mg daily, all with Ibrance. 

In the pooled population given amcenestrant at 200 mg daily, all 35 patients hit an ORR of 34%, with confirmed partial responses in 12/35 patients, and the CBR was 74%.

The trial also saw a “favorable overall safety profile” with no “clinically significant cardiac or ocular safety findings,” which has hit other drugs in this class.

The therapy works as an SERD that antagonizes and degrades the estrogen receptor (ER), resulting in inhibition of the ER signaling pathway. Sanofi kick-started a phase 3 combo test in a first-line setting back in October and “is successfully recruiting patients,” the company said.

RELATED: Roche dumps lead asset from its $725M Seragon buy

Speaking ahead of the data drop, Peter Adamson, global head of oncology development and pediatric innovation at Sanofi, says there is a big unmet need here, given the lack of treatments for R+/HER2- MBC and the huge burden of breast cancer in general, one of the biggest cancer killers of women worldwide.

Adamson was happy with the safety profile, which he said was clean enough to go into further testing, and was especially pleased not to see heart or eye safety signals.

He also said the CBR being at 75% made the drug, in his opinion, a leader in the pack, with a disease control rate of 97%. “Only one patient had an initial progression,” he said. “All other patients had a least stable disease … I see this as oral endocrine backbone therapy for the future.

“So, between CBR and ORR, we believe these data strongly support our contention that this could be a best-in-class oral SERD, and backs up our desire to move this drug into earlier and earlier stages.”

Analysts at Jefferies said there was “impressive efficacy in combo with Ibrance,” adding that it believed a teens ORR was the hurdle for Ameera-1, “with 20+% a good outcome and hence 34% perhaps ‘best’ case.”

There was a sour note, however as it said that Ameera-3, a potential registrational study which aims to show amcenestrant is superior to physician's choice of therapy in a second-line setting, has been delayed from Q2 to second half of this year.

“We caution against inferring an outcome based on the delay but acknowledge the longer wait for this key catalyst does not help build confidence in establishing belief in the pipeline,” it added.

This isn’t the first SERD: That goes to AstraZeneca’s Faslodex, nearly 20 years old now and recently making blockbuster annual sales (pre-patent expiry), though Adamson notes that its intramuscular delivery, which is very painful, held sales back and spurned a search for an oral version.

This is the path Sanofi is now treading, although it is not alone; fellow European pharma Roche is also working on its SERD candidate, RG6171. Analysts at Jefferies said in a note to clients in 2020 that SERDs were “at least a $2 billion to $3 billion market opportunity.”

AZ is also working on a next-gen SERD in AZD9833, an integral part of its breast cancer strategy, while Radius Health’s elacestrant is also in the mix.

Roche did, however, dump several SERDs, including its midstage oral attempt ARN-810, which came out from the ill-fated buyout of Seragon back in 2017. It didn’t at the time say what went wrong, but it demonstrates the difficult path these therapies still tread.