For metastatic breast cancer patients who try and fail on multiple treatments, finding options to manage disease is a difficult proposition. AstraZeneca and Daiichi Sankyo hoped their antibody-drug conjugate could help that tough-to-treat population––and the FDA agreed to give it a shot despite a shaky safety profile. 

The FDA approved AstraZeneca and Daiichi's Enhertu (fam-trastuzumab deruxtecan-nxki) as a treatment for patients with inoperable or metastatic HER2-positive breast cancer who have already failed on at least two other treatments. AstraZeneca and Daiichi will jointly develop and sell the drug outside of Japan, where Daiichi holds exclusive rights.

Enhertu will likely launch in January at a per-patient cost of around $13,300 per month, SVB Leerink analyst Andrew Berens said in a note to investors Monday. At that price, Enhertu could reach $68 million in sales in 2020, with a peak sales estimate of $2.5 billion, Berens said.

In a phase 2 study dubbed Destiny, Enhertu shrank tumors in 61% of patients and eliminated them completely in 6%, Daiichi said. A 97% disease control rate included patients who saw some tumor shrinkage but not enough to be considered responders. 

Destiny patients had tried a median of six prior treatments but had essentially run out of options. Patients with HER2-positive breast cancer typically receive Herceptin (trastuzumab) and Perjeta (pertuzumab) from Roche's Genentech early in their treatment, and when they relapse, they can go on Kadcyla, Genentech’s HER2-targeting ADC. 

"Since the beginning of our clinical trial program four years ago, we have focused on the opportunity to transform the treatment landscape for patients with HER2 positive metastatic breast cancer, and we are extremely proud of how quickly we delivered Enhertu to patients in the U.S., as Enhertu represents one of the fastest developed biologics in oncology," Antoine Yver, Daiichi's global head of oncology R&D, said in a release.

Enhertu will come with a boxed label warning for interstitial lung disease (ILD) and embryo-fetal toxicity after 9% of Destiny patients developed an ILD during treatment. Nearly all of the Destiny patients (99%) experienced side effects, including nausea, vomiting and low white blood cell counts. Fifteen percent of patients decided to stop treatment due to side effects, according to the statement.  

Despite what could be "best-in-class" efficacy, Berens said the ILD warning could be a lasting issue for prescribing physicians. 

"We expect ILD will remain an area of particular focus for physicians, particularly as Enhertu attempts to move earlier in the clinical treatment paradigm within breast cancer," Berens wrote.

AstraZeneca bet up to $6.9 billion on Daiichi and Enhertu, forking over $1.35 billion upfront in March this year for a share of the product. The partners are also testing Enhertu in other HER2-expressing cancers, including gastric cancer, colorectal cancer and non-small cell lung cancer.

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