Dive Brief:
- The Food and Drug Administration has requested additional dose-ranging studies and monotherapy studies for Vertex Pharmaceuticals' VX-561, a once-daily potentiator in development as part of combination regimens for the treatment of cystic fibrosis (CF). This will delay the next step into more advanced studies.
- In Phase 2 triple combo studies of VX-561 with VX-659 or VX-445 and tezacaftor in people with one minimal function mutation, there were mean absolute improvements in ppFEV1 of 11.7% and 12.2% from baseline through week four of treatment for the VX-659- and VX-445-based combos, respectively.
- Vertex has confirmed that it intends to take VX-561 forward as part of a once-daily regimen.
Dive Insight:
Vertex is developing VX-561 as part of a combo therapeutics program that the biotech estimates could allow it to treat 90% of the CF population. Yet the FDA's request delays VX-561 until more information is known about it.
"While we believe that the results clearly support the hypothesis that VX-561 has a role in future once-daily triple combinations, the FDA has requested additional dose ranging for VX-561, including potential evaluations of monotherapy, before allowing evaluation of VX-561 in late-stage development. We look forward to updating you on our progress with our triple-combination regimens as we advance these programs," Reshma Kewalramani, Vertex's chief medical officer, said on an earnings call last week.
VX-561 is a deuterated form of Kalydeco (ivacaftor), with one or more hydrogen atoms replaced by a stable isotope of hydrogen known as deuterium. This structure has potential to create a drug that has only to be taken once-daily.
It's a small chemical change, but one that could be meaningful to Vertex's bottom line — provided the biotech can work through the added clinical work and longer timelines the come with new molecules. On a first quarter earnings call last week, CEO Jeffrey Leiden said that during discussions with the regulatory body, "it became clear to us that the way the FDA was looking at VX-561… that [it is] a new chemical entity."
Also on the call, Leiden confirmed that the FDA requests regarding VX-561 were behind Vertex's decision to push the VX-445/Kalydeco combo into later-stage investigations.
Kewalramani remains confident about VX-561's safety profile. "When we looked at the data from VX-561 in either the VX-659 program or the VX-445 program, what we [saw was] real consistency with regard to efficacy as well as a safety profile."
Leiden described the FDA's decision on requiring monotherapy data for VX-561 as "informative", and "[not] unreasonable," which could mean that he is expecting to have similar decisions made for future potentiators.
"Obviously, as compounds get more and more different and newer and newer, I think that they're going to have the same expectations for new chemical entities pretty much across the board," said Leiden.