FDA Expands Labels for 3 Vertex CFTR Modulators

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by Marta Figueiredo PhD |

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Vertex Pharmaceuticals, expanded labels

The U.S. Food and Drug Administration (FDA) has expanded the number of cystic fibrosis (CF)-related mutations considered responsive to and therefore eligible for Vertex Pharmaceuticals‘ three approved therapies.

With these approvals, the labels will be expanded for Trikafta (elexacaftor/tezacaftor/ivacaftor and ivacaftor), Symdeko (tezacaftor/ivacaftor and ivacaftor), and Kalydeco (ivacaftor), the company announced.

The decision comes three months after the FDA agreed to review Vertex’s regulatory applications seeking the label expansions for the three therapies, all CFTR modulators. These modulators rectify CFTR protein defects that result from certain CFTR mutations — the underlying cause of cystic fibrosis.

“The approval for expanded use of three of our CF medicines based on our well-established in vitro [cellular] model is a testament to the relentless commitment of our scientists to reach our goal of developing treatments for all people with CF,” Reshma Kewalramani, MD, Vertex’s CEO and president, said in a press release.

According to Vertex, more than 600 CF patients with rare, disease-causing CFTR mutations not previously covered by the FDA-approved treatments will now be eligible to receive therapies that target the underlying cause of their disease.

In addition, the decisions allow certain Kalydeco-eligible patients to gain access to Symdeko and Trikafta — while some of those currently eligible for Symdeko will now be able to access Trikafta as well. Vertex estimates that more than 1,100 CF patients in the U.S. currently eligible for Kalydeco or Symdeko may now have the option of an additional CFTR modulator.

“We remain as committed today to reaching every patient who might benefit from our medicines as when we first started out on this journey 20 years ago, and this important milestone now enables hundreds of people with CF access to a treatment option to address the underlying cause of their disease — many for the first time,” Kewalramani said.

Each of the three therapies contain one or more CFTR modulators and were previously approved in the U.S. to treat people with specific CF-causing mutations in the CFTR gene.

The label expansions were based on preclinical data from a validated cellular model of lab-grown cells with rare CF-causing mutations showing that many other rare CFTR mutations also respond to one or more of these CFTR modulators. These findings have led to the inclusion of between 50 to 170 additional eligible mutations to these therapies.

Trikafta is now approved for CF patients, ages 12 and older, with at least one of 178 CFTR mutations — 177 of which are newly approved. Symdeko will now be available to patients 6 years and older with one of 154 mutations, including 127 that are now added. Meanwhile, Kalydeco can be prescribed for individuals who are ages 4 months and older and have one of 97 CF mutations, including 59 newly approved.

The full list of eligible mutations can be found here (page 8) for Trikafta, here (page 8) for Symdeko, and here (page 7) for Kalydeco.

In addition, people with CF and their families can search eligibility for Vertex CF medicines through vertextreatments.com.

Notably, data from this cellular model also contributed to the inclusion of 23 additional rare CFTR mutations to Kalydeco’s U.S. label in 2017. These decisions highlight the progress of cellular models to predict whether people with CF will respond to approved CFTR modulators.

Based on positive data from a Phase 3 trial, Vertex is also seeking to expand Trikafta’s approval in the U.S. to include children as young as age 6. The company is planning to file such an application to the FDA by the end of the year, with submissions to other regulatory agencies around the world to follow.


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