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

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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 
Astrazeneca/
Daiichi
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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