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When drug developers start using terms like “functional cure”, the science has arrived – or is at least pretty close. Reaching this point requires tinkering with different combinations and mechanisms of action.
For chronic lymphocytic leukemia and mantle cell lymphoma, many of these combinations include ibrutinib (Imbruvica).
Co-developed by J&J’s Janssen and AbbVie’s Pharmacyclics, ibrutinib stood out across several presentations at the 64th American Society of Hematology (ASH) annual meeting Saturday and Sunday.
In the U.S., the average five-year survival rate for CLL is 87%. While this may sound hopeful, there are still patient populations with high unmet needs, elderly patients in particular.
For MCL, the survival statistics aren’t as rosy. Janssen characterizes MCL, a form of non-Hodgkin’s lymphoma, as “an aggressive and incurable blood cancer of the white blood cells.”
Mark Wildgust_JanssenIn an interview with BioSpace, Mark Wildgust, vice president, global medical affairs, oncology at Janssen said ibrutinib is the only Bruton’s tyrosine kinase (BTK) inhibitor that has shown single agent overall survival benefit for patients with newly diagnosed CLL. The therapy won FDA approval as a single agent to treat second-line CLL in 2014.
A Functional Cure?
Of note, an oral presentation Saturday highlighted four-year follow-up data from the Phase III GLOW study. This trial tested a combination of ibrutinib plus AbbVie’s venetoclax versus chlorambucil plus obinutuzumab in 211 older adults with previously untreated CLL. These patients had comorbidities such as renal impairment.
The data showed ibrutinib plus venetoclax reduced the risk of progression or death by 79%. It is the first fixed-duration novel combination to demonstrate an overall survival advantage compared to chlorambucil plus obinutuzumab in the first-line treatment of CLL, Janssen reported.
Venetoclax is approved as a second-line treatment for CLL. It is also approved to treat adults 75 and older with newly diagnosed acute myeloid leukemia, in combination with azacitidine or decitabine or low-dose cytarabine.
Wildgust said the OS curve overlaps with an age-matched U.S. general population.
“The curve speaks thousands of words, in my mind,” he said. “To be able to return survival back to potentially what we would see in the normal patient population, I think speaks to the transformational outcomes we’ve been hoping for. In many regards, it’s almost like a functional cure.”
