SABCS 2019 – Macrogenics finds some better Herceptins are better than others

Data from the Sophia trial of Macrogenics’ margetuximab, presented at the San Antonio Breast Cancer Symposium today, underline what was already fairly clear: of the anti-Her2 projects intended to be a “better Herceptin”, Astrazeneca and Daiichi Sankyo’s antibody-drug conjugate, trastuzumab deruxtecan, is way out ahead. Margetuximab could show no overall survival advantage over Herceptin at the second interim analysis of Sophia data, with a median OS of 21.6 months versus 19.8 months for Roche’s drug. The final pre-specified OS analysis of Sophia is expected in the second half of 2020, by which time trastuzumab deruxtecan will almost certainly be approved in the third-line setting. The table below summarises data from various studies conducted in late-line breast cancer patients, and while such a comparison is imperfect it clearly shows trastuzumab deruxtecan trouncing the others. It also shows that the sellside has made up its mind in terms of which horse to back.

Cross-trial comparison of anti-Her agents 
Company Agent Trial ORR Median PFS (months) Median DoR (months) 2024e WW sales 
Trastuzumab deruxtecan Destiny  60.9% 16.4 14.8 $2bn
Roche Kadcyla  Emilia  43.6% 9.6 - $1.9bn
Macrogenics Margetuximab  Sophia  22.1% 5.8 6 $293m
Puma  Nerlynx Nala 32.8% 8.8 8.5 $283m
Seattle Genetics  Tucatinib  Her2Climb 40.6% 7.8 - $268m
ORR=objective response rate. PFS=progression-free survival. DoR=duration of response.
Source: EvaluatePharma; NEJM; company statements; SABCS.

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