Roche has famously refused to buy into cell therapy, and last year it went as far as trumpeting the fact that its anti-CD79b antibody-drug conjugate polatuzumab vedotin generated efficacy in relapsed lymphoma similar to that of CAR-T therapy. Yesterday the US FDA endorsed the enthusiasm, approving the drug as Polivy for third-line diffuse large B-cell lymphoma in combination with bendamustine. The GO29365 study on which approval is based had shown a remarkable 65% reduction in risk of death (p=0.0008) at the 2017 Ash meeting, but this included some second-line subjects, and the label cites only the overall remission surrogate – 45% versus 18% for bendamustine alone. Polivy is a largely overlooked asset, but Roche will rely on it as part of its haem-onc armamentarium, along with Gazyva, Venclexta and mosunetuzumab. CD79b is part of the B-cell receptor complex, so targeting it offers the possibility of knocking out B cells. A separate Roche asset, DCDS0780A, has yielded impressive monotherapy activity, but is even more obscure than Polivy. The only other industry asset targeting CD79b appears to be Provention Bio/Macrogenics’ PRV-3279; this is in development for lupus on the premise that it can stimulate a negative feedback loop on B cells.
|Selected industry assets targeting CD79b|
|Polivy||Roche/Seattle Genetics||Anti-CD79b ADC||NCT02257567||mOS 11.8mth vs 4.7mth in ≥2L lymphoma|
|DCDS0780A||Roche||Anti-CD79b Thiomab ADC||NCT02453087||ORR 60% (CR 43%) in DLBCL subgroup|
|PRV-3279||Provention/Macrogenics||Anti-CD32B x CD79b bispecific||NCT02376036||Earlier development by Takeda abandoned; current focus is lupus|