Kaftrio approved for eligible children with CF, ages 2-5, in EU

CFTR modulator plus Kalydeco for patients with at least one F508del mutation

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The European Commission has expanded the approval of Kaftrio (ivacaftor, tezacaftor, and elexacaftor) in combination with Kalydeco (ivacaftor) to include children ages 2 to 5 with cystic fibrosis (CF) who have at least one F508del mutation in the CFTR gene.

Previously cleared to treat patients ages 6 and older in the European Union (EU), the expansion of Vertex Pharmaceuticals’ CFTR modulator therapy will make the medication available to over 1,200 young children in Europe, according to the company.

A similar expansion in the U.K. recently was approved by regulators there. In the U.S., the therapy is known as Trikafta and also approved for CF patients 2 and older; it does not have to be used with Kalydeco.

“As CF starts in early childhood and is a progressive disease, it is important to treat people with CF as early as possible,” Marcus A. Mall, MD, head of pediatric respiratory medicine, immunology, and critical care at Charité Universitätsmedizin Berlin, said in a company press release.

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“With the approval of KAFTRIO for children as young as 2 years, we can now treat young children with a medicine that has the potential to slow disease progression by addressing the underlying cause of the disease,” Mall added.

Existing reimbursement agreements in Austria, Denmark, Ireland, Norway, Latvia, and Sweden mean that eligible patients in these countries quickly will have access to the treatment, while Vertex reported that it is working with authorities in other EU countries to enable similar access. A reimbursement agreement also is in place in the U.K.

CF is caused by mutations in the CFTR gene, leading to a missing or dysfunctional CFTR protein. Kaftrio is an oral combination of three CFTR modulators — elexacaftor, tezacaftor, and ivacaftor — that together work to boost CFTR function in patients with eligible mutations.

The expanded approvals are backed by data from a Phase 3 trial (NCT04537793) that demonstrated the therapy could effectively reduce sweat chloride concentrations and improve lung function among children ages 2-5 with at least one F508del mutation, the most common type of CF-causing mutations.

The therapy had a similar safety profile as in older patients, with common side effects including cough, fever, and a runny nose.

“In addition to data from clinical trials, long-term and real-world data have demonstrated the significant clinical benefit of Kaftrio in eligible people living with CF, and today’s news means that young children across Europe can now benefit from this important medicine,” said Carmen Bozic, MD, chief medical officer and executive vice president, global medicines development and medical affairs at Vertex.

Vertex requesting Kaftrio’s use in select patients with rarer mutations

In the EU, Kaftrio combined with Kalydeco is approved for patients with at least one copy of F508del.

European regulators recently agreed to review a request to expand the medication’s label to include people with more rare mutations who show a response to the treatment in clinical and laboratory studies.

That would include N1303Kwhich is among the most common of rare CF-causing mutations. Recent findings in patients with the N1303K mutation treated off-label indicated responses to treatment.

Vertex reports that this application includes positive safety and efficacy findings from a Phase 3 trial involving patients with non-F508del mutations treated with Kaftrio plus Kalydeco, as well as data from laboratory studies and real-world clinical findings collected from the CF Foundation Patient Registry in the U.S.

“It is encouraging to see such positive clinical trial results for KAFTRIO in people with CF with these rare types of mutations,” Isabelle Fajac, MD, PhD, a pulmonologist and professor at Cochin Hospital, Assistance Publique-Hôpitaux de Paris, and Université Paris Cité in France, said in a separate press release.

“The majority of these people currently have no treatment option to address the underlying cause of their CF, so this submission is an extremely important step towards a medicine becoming available for these people with high unmet medical needs,” Fajac added.

The company plans to submit similar regulatory filings in Australia, Brazil, Canada, New Zealand, and Switzerland.

In the U.S., Trikafta is approved for patients who carry at least one copy of F508del or any of 177 other CF-causing mutations shown to respond to the therapy in lab studies. Vertex plans to request that Trikafta’s U.S. use be further expanded to include patients with the N1303K mutation and others not already indicated.

“We are committed to going the distance in cystic fibrosis and dedicated to bringing treatments to all people with CF,” said Nia Tatsis, PhD, executive vice president, chief regulatory and quality officer at Vertex.