J&J study halt reveals a crisis in follow-on antibody approaches

The quiet suspension of enrolment into a phase I trial of Johnson & Johnson/Genmab’s anti-CD123 bispecific, JNJ-63709178, marks the second time this asset has been put on clinical hold. J&J would not tell EP Vantage the reasons for the suspension, beyond confirming the grade 3 adverse event listed in the Clinicaltrials.gov database. The previous hold, also due to an undisclosed serious adverse event, lasted seven months before being lifted in April 2017. JNJ-63709178’s troubles look like the tip of the iceberg for follow-on antibody approaches such as bispecifics and antibody-drug conjugates (ADCs), many of which have recently hit the buffers. A phase I trial of Seattle Genetics’ CD123-targeting ADC, SGN-CD123A, was terminated in May, while last year J&J handed the CD19-targeting bispecific duvortuxizumab back to its originator, Macrogenics. Though one of the leading players, ADC Therapeutics, recently started a pivotal phase II study of its anti-CD19 ADC, ADCT-402, in total 10 ADC projects have suffered setbacks so far this year.

Selected recent setbacks for antibody-drug conjugates and bispecifics
Project Target, approach Developer(s) Setback Date reported
JNJ-63709178 CD123, bispecific J&J/Genmab Phase I study on second clinical hold Jul 2018
XMT-1522 Her2, ADC Mersana Therapeutics Phase I study on clinical hold Jul 2018
RG7882 Muc16, ADC Roche/Seattle Genetics Discontinued Jul 2018
Denintuzumab mafodotin CD19, ADC Seattle Genetics Two phase II studies terminated Jul 2018
HKT288 CDH6, ADC Novartis/Immunogen Phase I study terminated Jun 2018
ADCT-401/MEDI3726 PSMA, ADC Astrazeneca/ADC Therapeutics Phase I study suspended Jun 2018
SGN-CD123A CD123, ADC Seattle Genetics Phase I study terminated May 2018
ADCT-502 Her2, ADC ADC Therapeutics Phase I study terminated Apr 2018
Glembatumumab vedotin GPNMB, ADC Celldex Discontinued Apr 2018
SC-007 Undisclosed, ADC Abbvie Phase I study terminated Apr 2018
AGS67E CD37, ADC Astellas Phase I study suspended Mar 2018
Duvortuxizumab  CD19, bispecific J&J/Macrogenics Phase I study terminated, deal scrapped Aug 2017
Source: company documents & clinicaltrials.gov.

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