MacroGenics' breast cancer drug Margenza erases edge over Herceptin as it fails to extend life

Failure to show a survival advantage over Herceptin is a blow to Margenza’s already meager commercial outlook in HER2-postive breast cancer. (nito100 /iStock/Getty Images Plus)

A key message MacroGenics had for Margenza was that the HER2 drug topped Roche’s Herceptin in breast cancer patients. But now, that advantage is no more.

A combination of Margenza and chemotherapy failed to help previously treated HER2 breast cancer patients live longer compared with Herceptin’s pairing with chemo, MacroGenics said Tuesday.

Among patients who had at least two prior treatments, those who took the Margenza regimen lived a median 21.6 months, while patients on Herceptin plus chemo lived a median 21.9 months.

The disappointing result came from the same phase 3 SOPHIA study that had previously shown the Margenza regimen performed better than the Herceptin therapy at staving off disease progression or death. Margenza won FDA’s approval in third-line-plus HER2-postive breast cancer in December 2020 with that showing.

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Failure to show a survival advantage over Herceptin is a blow to Margenza’s already meager commercial outlook. Before the flop, SVB Leerink analyst Jonanthan Chang projected Margenza 2028 sales in the currently approved indication would be a mere $94 million for MacroGenics. Zai Lab holds the drug’s greater China rights.

MacroGenics itself doesn’t see much potential in Margenza. As MacroGenics CEO Scott Koenig, M.D., Ph.D., reiterated during a conference call late July, the company has “modest expectations” for Margenza sales given the competitive landscape in the HER2-positive breast cancer market. In the second quarter, Margenza’s sales checked in at $3.2 million; it launched mid-March.

In Tuesday’s announcement, Koenig pointed to several exploratory analyses to show Margenza might work better in certain patient subgroups.

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Similar to previous observations from the progression-free survival data, Margenza’s benefit appears to be enhanced in carriers of the CD16A-158F genetic marker, as it prolonged median survival by 2.5 months in this subgroup, which made up about 82% of study population.

Even within the CD16A-158F genotype, there were major differences across allele subsets, with some patients performing notably worse on Margenza.

“Therefore, further studies are warranted to determine the impact of Margenza on HER2-positive breast cancer patients with different CD16A allelic variants,” Koenig said in a statement. “We continue to believe Margenza may be the right choice for certain patients.”

Besides heavily pretreated HER2 breast cancer, MacroGenics will present early data from cohort A of the phase 2/3 MAHOGANY trial at the upcoming European Society for Medical Oncology meeting. The trial is paring Margenza with the Incyte-partnered PD-1 inhibitor retifanlimab in HER2-positive stomach cancer.