Vertex Shares Boom on Cystic Fibrosis Results

5/7/12Follow @xconomy

[Updated: 9:40 am ET] Vertex Pharmaceuticals wowed the cystic fibrosis community earlier this year with its new drug that improves lung function for patients with a rare form of the inherited disease. Now it’s gathering evidence that it could extend the drug’s benefits to many more people.

The Cambridge, MA-based company (NASDAQ: VRTX) is announcing today that a combination of its ivacaftor (Kalydeco) therapy and an experimental drug called VX-809 was able to provide a significant improvement in lung function for adult patients with the most common genetic mutation in CF, known as F508del. (Ivacaftor is currently approved to treat patients with a mutation called G551D, which affects about 4 percent of people with CF.) The data is based on an early peek at an ongoing study, and only includes 48 patients out of 108 expected to enroll, so it’s far from the final answer researchers are looking for. But it’s enough of an encouraging sign that Vertex plans to advance the combo regimen into the third and final phase of clinical trials normally required for FDA approval, after it analyzes the final data this summer.

[Updated with stock movement.] Vertex shares shot up by $16.26 a share, or 44 percent, to $53.67 after the opening of trading today.

“I’m encouraged, and I’d be very, very happy if these data hold up to the end of trial,” says Michael Boyle, the director of the Johns Hopkins Adult Cystic Fibrosis Center, and the study’s lead investigator.

Michael Boyle, director of the Johns Hopkins Adult Cystic Fibrosis Center

Cystic fibrosis, the result of mutations to a gene called CFTR, causes the poor transfer of water and salt across cell membranes, which leads to the buildup of thick, sticky mucus in the lungs. That effectively suffocates people over time, and often ends up killing people in their late 30s or early 40s. Doctors have made significant progress over the years through improved treatment of CF symptoms, but in January, Vertex’s ivacaftor became the first FDA-approved therapy that works by targeting the CFTR protein directly; the drug helps prop open these cellular gateways to allow better transport of ions across cell membranes.

The problem for most people with cystic fibrosis, though, is that their genetic form of the disease prevents CFTR proteins from getting close enough to the cell surface to benefit from the effect of ivacaftor. That’s where VX-809 enters the picture. It is supposed to work by helping shuttle the CFTR protein toward the cell surface, where ivacaftor is opening the doors to effective transport. If the two drugs are found to be effective together, it could be another major advance for cystic fibrosis.

“There’s a ton of enthusiasm in the community, because of the success with Kalydeco, and because we don’t have any other therapies that address the underlying cause,” Boyle says.

The data is still preliminary, though. Researchers saw that 17 of 37 patients (46 percent) who started on VX-809 and then got a combo of VX-809 and ivacaftor had at least a five percentage point absolute improvement in lung function after 56 days. While that benchmark is considered clinically meaningful, Boyle says he was even more impressed to see 11 of the 37 patients (30 percent) experience a 10 percent absolute improvement in lung function. None of the 11 patients receiving a placebo in the study reached either threshold of lung function improvement. That means the difference between those on the new drugs and the placebo was both statistically significant (not a fluke) and clinically important, Boyle says. The adverse events in the study were mild to moderate, and comparable between those on the Vertex drugs and those on the placebo, the company said.

The results from this study don’t apply to everyone with CF. The study results were from patients with two bad copies of the F508del gene, meaning they are in the so-called homozygous camp. The study also enrolled patients with one bad copy of the F508del gene, meaning they are in the heterozygous group. Results from 21 heterozygous patients on the combo therapies are being evaluated, but Vertex said it doesn’t yet have enough data to draw any conclusions.

About half of all cystic fibrosis patients have two faulty copies of the F508del gene while about 87 percent are thought to have at least one bad copy of the F508del gene, Boyle says. So if Vertex can show the two drugs benefit larger numbers of patients in the ongoing trial, and reproduce the findings in another trial, it could potentially benefit the vast majority of the 30,000 patients in the U.S. with the disease. “That’s why this trial is the one we are focused on and a lot of people in the CF community are so focused on,” Boyle says.

Researchers were surprised to see a benefit on lung function from a small study that was designed to primarily assess safety and the amount of sweat chloride ions on the skin—which can be an early sign of a CF drug that’s working. But questions remain. Researchers haven’t yet determined the ideal dosing regimen, Boyle says. And the average absolute improvement in lung function isn’t being released yet, because the study is still preliminary, and researchers don’t want patients to fixate on a number that can’t yet be entirely established.

If Vertex can show that the two drugs can consistently deliver around a 10 percent absolute improvement in lung function—which ivacaftor did—then Boyle says he’ll be “ecstatic.” While a 10 percent absolute improvement might not sound like much, it can make a big difference. As examples, Boyle said a person who improves from 20 percent lung function to 30 percent goes from the verge of a lung transplant to having a longer life expectancy, Boyle says. An improvement from 40 percent lung function to 50 percent clearly enables a patient to exercise more. A person going from 50 percent to 60 percent can feel a significant difference when climbing stairs, he says.

Now that ivacaftor has shown that kind of improvement in lung function, the next major question for researchers is what difference it makes in long-term quality of life and survival times. The same would be true for a two-drug combo. And if the two-drug combo passes all its clinical trials, there will have to be a lot of thought given to prices. Ivacaftor, a chronic therapy taken twice a day, costs $294,000 per year per patient, for a disease that young people can live with for many years. Any new agent that extends ivacaftor-like improvement to a much larger population of CF patients is also bound to add significant cost.

But those questions will surely be dealt with in more depth another day. For today, the focus will be on what the interim data says about a promising new treatment approach for CF, and the next steps in development. The company is planning to host a conference call at 8:30 am ET today with analysts and media to discuss the data in more detail.

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