A surprise FDA approval allowing Vertex Pharmaceuticals Inc. to expand the label for its cystic fibrosis (CF) therapy, Kalydeco (ivacaftor), to include an additional 3 percent of the CF population with certain rare residual function mutations boosted forecast sales for the therapy and lent credence to the potential power of in vitro assays to sway the agency in certain cases.

The approval follows a February 2016 complete response letter that initially blocked a supplemental new drug application in which Vertex sought the label expansion. The Boston-based company said little about the status of the pursuit prior to announcing the regulatory win. The change increases the number of transmembrane conductance regulator (CFTR) gene mutations that the drug is now approved to address to 33 mutations from a prior 10, potentially adding more than 900 people, ages 2 and older, to the therapy's addressable U.S. market. Before now, it was indicated only for mutations that occur in about 8 percent of CF patients.

There are nearly 2,000 known mutations that can affect the CFTR gene, but only about 300 of them result in CF.

The FDA said it based its decision, in part, on the results of in vitro laboratory testing, which it used in conjunction with evidence from earlier clinical trials. "Many rare cystic fibrosis mutations have such small patient populations that clinical trial studies are not feasible," said Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research (CDER). "This challenge led us to using an alternative approach based on precision medicine, which made it possible to identify certain gene mutations that are likely to respond to Kalydeco."

In a separate statement, other representatives of CDER said a comprehensive understanding of the genetics of CF and the function of the CFTR channel also helped. Broadening the potential takeaway for drugmakers, they also suggested that the approval should signal to other sponsors that "for drugs that target specific mutations, in vitro assay data could potentially be used in place of additional small clinical trials when seeking to expand to other population subsets, provided that the drug's safety profile is good, the disease is well-characterized and other criteria are met."

Vertex said the development was likely to grow its 2017 product revenues from Kalydeco sales to a range of $740 million to $770 million from prior guidance of $710 million to $730 million, announced during the company's first-quarter earnings call in late April. The company did not respond to a request for further comment.

Despite the win, UBS Securities analyst Carter Gould suggested that more important data regarding the company's midstage triplet regimens lay ahead. Vertex is evaluating four different next-generation correctors to be included in an investigational triple-combination regimen with tezacaftor and ivacaftor. Data on trials evaluating three of the combinations are due in the second half of this year.

The tezacaftor/ivacaftor combination on its own was validated in a phase III study of people who have one mutation that results in residual CFTR function and one F508del mutation. The study met its primary endpoint and the combination was generally well-tolerated. Vertex plans to submit data on that trial as part of an FDA new drug application and an EMA marketing authorization application early in the third quarter of 2017.

The triplets will build on that. One of the ongoing triplet studies is a phase II trial adding VX-152 to tezacaftor and ivacaftor in patients with two copies of the F508del mutation. A second phase II trial adding VX-440 and a phase I trial adding VX-659 are also progressing as planned, the company said last month. Data from all three studies are expected in the second half of 2017. The fourth trial, a phase I testing the addition of VX-445, is expected to yield data in early 2018.

In addition to the new mutations added to Kalydeco's label, Vertex said it is continuing discussions with the FDA concerning the approval for additional people who have mutations responsive to Kalydeco, including one of five splice mutations that were evaluated as part of the company's phase III Expand study. During that trial, the Kalydeco monotherapy arm met its primary efficacy endpoint while being generally well-tolerated. More than 600 people ages 2 and older in the U.S. have one of the five mutations.

Vertex shares (NASDAQ:VRTX), which fell $3.71 during trading on Wednesday, regained some lost ground following the announcement, rising $3.55 to close at $117.93 on Thursday.