Roche partners with Roche on 'breakthrough' PD-L1 cancer program

CHICAGO--Considering the media din surrounding the big immuno-oncology PD-1 drugs at Merck ($MRK) and Bristol-Myers Squibb ($BMY), it's been almost quiet when it comes to Roche's rival PD-L1 drug MPDL3280A. But don't let the low-key pitch fool you. The giant R&D machine at Genentech has been laboring in this field since 2000, when the company originally identified PD-L1 as a target worth exploring. And it's been moving faster than some people might think, with an ambitious internal combo strategy focused on both approved drugs and experimental therapies.

Today, Roche ($RHHBY) put out the word that their program won the FDA's coveted breakthrough therapy designation, potentially putting it on an inside track at the agency, which has been hurrying along new medicines in the pipeline.

Dan Chen, who heads up the MPDL3280A program at Genentech, was on hand at ASCO to review the latest progress with this therapy, reporting promising tumor responses from 13 of 30 PD-L1-positive patients with advanced urothelial bladder cancer. With a 43% response rate and evidence of a durable effect that can hold cancer at bay, Genentech is already in Phase II. And they're wide open to using that to back an application at the FDA--if it's positive enough.

"We were very specific in our selection of PD-L1," Chen says.

Genentech's anti-PD-L1 antibody--aimed at inhibiting the programmed death-ligand 1--doesn't just interact with receptors for PD-1, preventing a critical juncture involved in allowing cancer cells to evade the immune system. It also interacts with B7.1, which also plays a role in the process. Chen believes the PD-L1 approach has other distinct advantages over the PD-1 rivals.

PD-1 can also play a role in triggering an inflammatory response. "You see more lung inflammation" in PD-1, Chen says, which their drug can avoid. 

"These patients who respond, they continue to respond," Chen adds. And when you're dealing with metastatic, treatment-resistant cases, that's a major point in its favor.

A lot is at stake in this development effort. Some analysts have projected peak sales in the billions--normal for IO these days.

So far, Roche's bladder cancer program has been overshadowed by the frenetic pace of research at Merck and Bristol-Myers Squibb, which have been partnering up and accelerating their programs for multiple cancers.

In part, says Dietmar Berger, the new global head of clinical oncology/hematology, that's because Roche/Genentech already has a broad pipeline of cancer therapies. That's allowed the PD-L1 team to quietly start combo programs with therapies like Zelboraf, Tarceva and Avastin, as well as other experimental therapies that haven't been discussed at all. Altogether, Genentech has 11 clinical trials in four tumor types underway, with plans for more.

"Each combination we do, we want to do for a reason," Chen says.

That requires carefully inspecting nonresponding tumors as well as the responders, so they can see what the best combinations are.

Work on PD-L1 dates back to 2000, when Genentech originally uncovered PD-L1 as a target in cancer. That kind of time has allowed Genentech to do some very deliberate work on its antibody, which is critical in immuno-oncology. The wrong kind of antibody wouldn't just kill cancer cells, Chen says, it would also wipe out T cells.

Phase II has already begun, with plans to enlist about 300 patients with bladder cancer, an area of medicine that hasn't seen any major new advances in years. Midstage studies can often enroll slowly, Chen says, but this time around the lack of treatment options along with the extraordinary focus on the field are greasing the wheels. And that's just one of several factors that is accelerating the research work, which is also being assisted by FDA regulators who are clearly avid to see these drugs blitz through the research phase.

- here's the release

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