Vertex Pharmaceuticals said three triple-combination regimens of its cystic fibrosis (CF) treatments have succeeded in Phase I and Phase II trials, potentially expanding the universe of CF patients who could benefit from treatment—sparking a 25% surge in the company’s share price this morning.

The trials assessed the combination regimens—involving Vertex candidates VX-152, VX-440, and VX-659—on patients who have one F508del mutation, as well as patients with one minimal function mutation (F508del/Min).

Data from the studies showed approximately 90% of patients with CF could potentially be positively impacted by the new treatments, Jefferies analyst Michael Yee and Steven Rowe, M.D., director of the University of Alabama at Birmingham’s Gregory Fleming James Cystic Fibrosis Research Center, said in separate statements.

Added Dr. Rowe: “These are the first data to demonstrate the potential to treat the underlying cause of CF in these patients, who have a severe and difficult-to-treat type of the disease.”

Dr. Rowe co-chairs a steering committee of global CF experts and clinical trial investigators formed to support the design, conduct, and execution of the triple-combination pivotal study program; the other co-chair is Jennifer Taylor-Cousar, M.D., of National Jewish Health in Denver. Dr. Rowe’s center was a study site for one of the three regimens studied, involving VX-152.

Following the positive news, Vertex shares jumped in premarket trading from yesterday’s closing price of $132.16, to $166.68 as of 9:10 a.m. before dipping to $165.39 as of 10:13 a.m. Jefferies raised its price target on Vertex shares, from $155 to $185, while maintaining a Buy rating.

Should data from ongoing and later trials prove as positive as the results announced yesterday, Jefferies analyst Yee said, Vertex could become the fastest-growing large-capitalization biotech, with earnings per share combined annual growth rate zooming from 0% now to 25% to 35% annually over the next five to eight years.

As a result, he added, Vertex could during that period more than double its peak annual revenue from CF drugs—from the $3 billion previously projected, to between $6 billion and $7 billion.

Vertex finished last year with $1.683 billion in total CF product revenues—consisting of $980 million from Orkambi® (Kalydeco® [ivacaftor] and lumacaftor) and $703 million from Kalydeco. For this year, Vertex has projected it will generate up to $2 billion from those products—between $1.1 and $1.3 billion for Orkambi and between $690 and $710 million for Kalydeco.

During Q1, revenue from CF drugs rose to a combined $481 million for Orkambi and Kalydeco, up 22% from the year-ago quarter. The two treatments can treat about 40% of the 75,000 CF patients in North America, Europe, and Australia.


Improved Pulmonary Function

The combination of VX-152 (200 mg q12h) or VX-440 (600 mg q12h) added to Kalydeco and Phase III candidate tezacaftor (VX-661) generated positive Phase II data—namely mean absolute improvements in percent predicted forced expiratory volume in one second (ppFEV1) of 9.7 and 12.0 percentage points from baseline, respectively, Vertex said.

The company also announced initial data from a Phase I study showing a mean absolute improvement in ppFEV1 of 9.6 percentage points from baseline for the triple-combination regimen of VX-659, tezacaftor, and Kalydeco in people with one F508del mutation and one minimal function mutation.

For patients with two copies of the F508del mutation, who were already receiving tezacaftor and Kalydeco, Vertex added that initial data showed improvements in mean absolute ppFEV1 of 7.3 and 9.5 percentage points following the addition of VX-152 or VX-440, respectively.

The company also announced today initial data showing improvements in mean absolute ppFEV1 of 7.3 and 9.5 percentage points when VX-152 or VX-440 was added in patients with two copies of the F508del mutation, who were already receiving tezacaftor and Kalydeco.

Vertex said the triple-combination regimens were generally well tolerated across all three studies, with the majority of adverse events being mild to moderate in severity. Two treated patients showed elevated liver enzyme levels that returned to normal after treatment discontinuation or completion.

“These safety and efficacy data are clear and compelling, indicating significant potential benefit for people with CF from each of these three different triple-combination regimens,” Jeffrey Chodakewitz, M.D., Vertex evp and CMO, said in a statement. “We will be collecting and evaluating additional data from these and other studies and will make a decision on which regimen(s) to take forward into pivotal program(s), which we expect to begin in the first half of 2018.”


4 Correctors Under Development

Vertex is developing four next-generation correctors as it seeks to advance one or more triple-combination regimens for patients with CF—the three candidates assessed in the trials, plus VX-445.

The company said it has launched a Phase II study of VX-445, and plans to do likewise with VX-659 in early August. VX-445 and VX-659 will be evaluated in triple combination with tezacaftor and ivacaftor in people with one F508del mutation and one minimal function mutation and will be evaluated in people with two copies of the F508del mutation who are already receiving tezacaftor and ivacaftor.

Data from both Phase II studies is expected in early 2018. Also, in the first half of next year, Vertex plans to initiate pivotal development of one or more triple-combination regimens—pending additional data from these studies, plus the ongoing studies of VX-152 and VX-440 and discussions with regulatory agencies and the trials’ steering committee.

“Patients with minimal function mutations have been waiting for a medicine to treat the underlying cause of their disease, which makes these data showing pronounced improvements in lung function particularly important,” Dr. Rowe added.