
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 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. |