Vertex execs whip up a cheer from the analysts after hedging their bet by picking their two top triples for PhIII

Vertex mapped out its late-stage strategy for a new triple therapy for cystic fibrosis on Wednesday evening, earning considerable applause from an appreciative group of analysts covering the biotech.

Jeff Leiden

The biotech’s $VRTX executive team has stoked blockbuster hopes around these combination studies, key to their plan to broaden the scope of patients they can cover, and they did their best to keep expectations high as rivals look to carve into the market.

In the end, the team clearly likes VX-659 in combination with tezacaftor and Kalydeco, noting that their Phase II data demonstrated that the high dose improved a measure of lung function by 13.3%.

That helped earn a 6% boost in their stock price in after-market trading.

But with the company’s future being built on the outcomes of the Phase III studies to come, they also want to pursue a Phase III trial that matches another experimental therapy, VX-445, for the triple — though that trial will get started after the 659 study gets underway.

Why two Phase IIIs?

“(W)e’re taking two forward because that’s one way of modifying one risk and that’s the risk of some rare off target toxicity due to the next-gen corrector in one of these regimens and obviously by taking two forward, we mitigate that risk,” CEO Jeff Leiden told analysts during the quarterly call.

The 445 triple actually just barely edged out 659 for the high-dose response, with a 13.8% improvement in FEV1. But the second highest dose only came in at a single-digit improvement rate, with a lower rate of reduction for sweat chloride as well as two troubling discontinuations in one of the drug arms.

“(A)t the margin, VX-659 looks to be the cleaner and more effective of the two molecules, although the patient numbers are still small (40-50 patients per trial),” noted Leerink’s Geoffrey Porges Thursday morning. “The company appears to be focusing on VX-659 as the preferred second generation corrector combination partner for further development, although VX-445 is also being advanced into pivotal trials. The first triple combination pivotal trial (VX-659+ Tez/Iva) will begin in Q2, pending finalizing study design with the FDA, and will initially focus on het min patients, although pivotal trials in homozygous delF508 patients are likely to be only a few months behind. Vertex expects to start a second pivotal trial program with VX-445 in mid year, most likely incorporating VX-561, (deuterated ivacaftor licensed from Concert) and consisting of all medicines dosed on a once daily basis.”

“The data announced today are remarkable and demonstrate the potential for significant and consistent clinical benefits in patients with one F508del mutation and a minimal function mutation when treated with a triple combination regimen containing either VX-659 or VX-445,” noted Leiden.

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Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
Director of Operations
Atlas Venture Cambridge, MA

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