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A new indication for the tyrosine kinase inhibitor nintedanib approved by the Food and Drug Administration on March 9, 2020, broadened the drug’s targeted population to include patients with chronic fibrosing interstitial lung diseases with a progressive phenotype.

FDA icon

This new group of patients eligible for nintedanib treatment extends the drug’s labeling beyond patients with idiopathic pulmonary fibrosis (IPF) or interstitial lung disease (ILD) associated with systemic sclerosis or scleroderma, and may come close to doubling the total number of eligible patients.

The new, expanded indication “helps to fulfill an unmet treatment need, as patients with these life-threatening lung diseases have not had an approved medication until now,” said Banu Karimi-Shah, MD, acting deputy director of the division of pulmonary, allergy, and rheumatology products in the FDA’s Center for Drug Evaluation and Research, in a written agency statement that announced the new indication.

The FDA first approved nintedanib (Ofev) for treating IPF in October 2014, and then granted a second indication in September 2019 for ILD associated with systemic sclerosis or scleroderma.



A recent assessment of 1,285 Canadian patients diagnosed with fibrotic ILD and entered into a national registry (CARE-PF) showed that IPF was the associated diagnosis for 25% of patients, and that the majority of patients had other primary diagnoses such as connective tissue disease ILD in 33% of enrolled patients, unclassifiable ILD in 22%, chronic sensitivity pneumonitis in about 8%, sarcoidosis in 3%, as well as other types (BMC Pulm Med. 2019 Nov 27. doi: 10.1186/s12890-019-0986-4).

It remains unclear right now what percentage of patients with fibrotic ILD have the progressive form that would make them eligible for nintedanib treatment under the new indication, but it’s probably about another quarter of the entire ILD population, or roughly similar to the number of patients with an IPF etiology who are already eligible to get the drug, commented Martin Kolb, MD, a professor of respirology at McMaster University, Hamilton, Ont., and a coinvestigator on the CARE-PF registry. A goal of the registry, which has now enrolled nearly 3,700 ILD patients, is to track them serially to get a better handle on the prevalence of progressive disease. The percentage of patients with ILD associated with systemic sclerosis or scleroderma is “relatively small,” compared with these other two patients subgroups, Dr. Kolb said in an interview.

The evidence base for treating patients with progressive ILD is “really strong,” he noted, and comes primarily from a major trial reported last year – the INBUILD study – that randomized 663 patients to treatment with either nintedanib or placebo and showed that nintedanib treatment significantly cut the rate of decline in forced vital capacity during 1 year of treatment (New Engl J Med. 2019 Oct 31;381[18]:1718-27). The patients entered the study as referrals from routine practice with documented ILD with progressive fibrosis that was not responsive to treatment with steroids or other immunosuppressive drugs, and reflects real-world, community practice, Dr. Kolb said.



“Conceptually, it makes so much sense” to treat the patients enrolled in INBUILD, the same patients who fit the new indication, with an agent like nintedanib that slows fibrosis progression, and in some patients may bring progression to a virtual halt, said Dr. Kolb, a coinvestigator on the INBUILD study. Future treatment of these patients will likely involve coupling an antifibrotic drug like nintedanib with an anti-inflammatory agent, although combined treatment of this type needs more study, he noted. In the more than 5 years since nintedanib came onto the U.S. market, it has been used on more than 10,000 patients and has generated no new safety concerns beyond those first included in the drug’s label.

The INBUILD study was sponsored by Boehringer Ingelheim, the company that markets nintedanib. Dr. Kolb has been a consultant to, received honoraria from, and received research funding from Boehringer Ingelheim. He has also received consulting fees or honoraria from Genoa, Gilead, GlaxoSmithKline, Indalo, Prometic, Roche, and Third Pole, and he has received research funding from Actelion, Alkermes, Gilead, GlaxoSmithKline, Pharmaxis, Prometic, RespiVert, and Roche.

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A new indication for the tyrosine kinase inhibitor nintedanib approved by the Food and Drug Administration on March 9, 2020, broadened the drug’s targeted population to include patients with chronic fibrosing interstitial lung diseases with a progressive phenotype.

FDA icon

This new group of patients eligible for nintedanib treatment extends the drug’s labeling beyond patients with idiopathic pulmonary fibrosis (IPF) or interstitial lung disease (ILD) associated with systemic sclerosis or scleroderma, and may come close to doubling the total number of eligible patients.

The new, expanded indication “helps to fulfill an unmet treatment need, as patients with these life-threatening lung diseases have not had an approved medication until now,” said Banu Karimi-Shah, MD, acting deputy director of the division of pulmonary, allergy, and rheumatology products in the FDA’s Center for Drug Evaluation and Research, in a written agency statement that announced the new indication.

The FDA first approved nintedanib (Ofev) for treating IPF in October 2014, and then granted a second indication in September 2019 for ILD associated with systemic sclerosis or scleroderma.



A recent assessment of 1,285 Canadian patients diagnosed with fibrotic ILD and entered into a national registry (CARE-PF) showed that IPF was the associated diagnosis for 25% of patients, and that the majority of patients had other primary diagnoses such as connective tissue disease ILD in 33% of enrolled patients, unclassifiable ILD in 22%, chronic sensitivity pneumonitis in about 8%, sarcoidosis in 3%, as well as other types (BMC Pulm Med. 2019 Nov 27. doi: 10.1186/s12890-019-0986-4).

It remains unclear right now what percentage of patients with fibrotic ILD have the progressive form that would make them eligible for nintedanib treatment under the new indication, but it’s probably about another quarter of the entire ILD population, or roughly similar to the number of patients with an IPF etiology who are already eligible to get the drug, commented Martin Kolb, MD, a professor of respirology at McMaster University, Hamilton, Ont., and a coinvestigator on the CARE-PF registry. A goal of the registry, which has now enrolled nearly 3,700 ILD patients, is to track them serially to get a better handle on the prevalence of progressive disease. The percentage of patients with ILD associated with systemic sclerosis or scleroderma is “relatively small,” compared with these other two patients subgroups, Dr. Kolb said in an interview.

The evidence base for treating patients with progressive ILD is “really strong,” he noted, and comes primarily from a major trial reported last year – the INBUILD study – that randomized 663 patients to treatment with either nintedanib or placebo and showed that nintedanib treatment significantly cut the rate of decline in forced vital capacity during 1 year of treatment (New Engl J Med. 2019 Oct 31;381[18]:1718-27). The patients entered the study as referrals from routine practice with documented ILD with progressive fibrosis that was not responsive to treatment with steroids or other immunosuppressive drugs, and reflects real-world, community practice, Dr. Kolb said.



“Conceptually, it makes so much sense” to treat the patients enrolled in INBUILD, the same patients who fit the new indication, with an agent like nintedanib that slows fibrosis progression, and in some patients may bring progression to a virtual halt, said Dr. Kolb, a coinvestigator on the INBUILD study. Future treatment of these patients will likely involve coupling an antifibrotic drug like nintedanib with an anti-inflammatory agent, although combined treatment of this type needs more study, he noted. In the more than 5 years since nintedanib came onto the U.S. market, it has been used on more than 10,000 patients and has generated no new safety concerns beyond those first included in the drug’s label.

The INBUILD study was sponsored by Boehringer Ingelheim, the company that markets nintedanib. Dr. Kolb has been a consultant to, received honoraria from, and received research funding from Boehringer Ingelheim. He has also received consulting fees or honoraria from Genoa, Gilead, GlaxoSmithKline, Indalo, Prometic, Roche, and Third Pole, and he has received research funding from Actelion, Alkermes, Gilead, GlaxoSmithKline, Pharmaxis, Prometic, RespiVert, and Roche.

A new indication for the tyrosine kinase inhibitor nintedanib approved by the Food and Drug Administration on March 9, 2020, broadened the drug’s targeted population to include patients with chronic fibrosing interstitial lung diseases with a progressive phenotype.

FDA icon

This new group of patients eligible for nintedanib treatment extends the drug’s labeling beyond patients with idiopathic pulmonary fibrosis (IPF) or interstitial lung disease (ILD) associated with systemic sclerosis or scleroderma, and may come close to doubling the total number of eligible patients.

The new, expanded indication “helps to fulfill an unmet treatment need, as patients with these life-threatening lung diseases have not had an approved medication until now,” said Banu Karimi-Shah, MD, acting deputy director of the division of pulmonary, allergy, and rheumatology products in the FDA’s Center for Drug Evaluation and Research, in a written agency statement that announced the new indication.

The FDA first approved nintedanib (Ofev) for treating IPF in October 2014, and then granted a second indication in September 2019 for ILD associated with systemic sclerosis or scleroderma.



A recent assessment of 1,285 Canadian patients diagnosed with fibrotic ILD and entered into a national registry (CARE-PF) showed that IPF was the associated diagnosis for 25% of patients, and that the majority of patients had other primary diagnoses such as connective tissue disease ILD in 33% of enrolled patients, unclassifiable ILD in 22%, chronic sensitivity pneumonitis in about 8%, sarcoidosis in 3%, as well as other types (BMC Pulm Med. 2019 Nov 27. doi: 10.1186/s12890-019-0986-4).

It remains unclear right now what percentage of patients with fibrotic ILD have the progressive form that would make them eligible for nintedanib treatment under the new indication, but it’s probably about another quarter of the entire ILD population, or roughly similar to the number of patients with an IPF etiology who are already eligible to get the drug, commented Martin Kolb, MD, a professor of respirology at McMaster University, Hamilton, Ont., and a coinvestigator on the CARE-PF registry. A goal of the registry, which has now enrolled nearly 3,700 ILD patients, is to track them serially to get a better handle on the prevalence of progressive disease. The percentage of patients with ILD associated with systemic sclerosis or scleroderma is “relatively small,” compared with these other two patients subgroups, Dr. Kolb said in an interview.

The evidence base for treating patients with progressive ILD is “really strong,” he noted, and comes primarily from a major trial reported last year – the INBUILD study – that randomized 663 patients to treatment with either nintedanib or placebo and showed that nintedanib treatment significantly cut the rate of decline in forced vital capacity during 1 year of treatment (New Engl J Med. 2019 Oct 31;381[18]:1718-27). The patients entered the study as referrals from routine practice with documented ILD with progressive fibrosis that was not responsive to treatment with steroids or other immunosuppressive drugs, and reflects real-world, community practice, Dr. Kolb said.



“Conceptually, it makes so much sense” to treat the patients enrolled in INBUILD, the same patients who fit the new indication, with an agent like nintedanib that slows fibrosis progression, and in some patients may bring progression to a virtual halt, said Dr. Kolb, a coinvestigator on the INBUILD study. Future treatment of these patients will likely involve coupling an antifibrotic drug like nintedanib with an anti-inflammatory agent, although combined treatment of this type needs more study, he noted. In the more than 5 years since nintedanib came onto the U.S. market, it has been used on more than 10,000 patients and has generated no new safety concerns beyond those first included in the drug’s label.

The INBUILD study was sponsored by Boehringer Ingelheim, the company that markets nintedanib. Dr. Kolb has been a consultant to, received honoraria from, and received research funding from Boehringer Ingelheim. He has also received consulting fees or honoraria from Genoa, Gilead, GlaxoSmithKline, Indalo, Prometic, Roche, and Third Pole, and he has received research funding from Actelion, Alkermes, Gilead, GlaxoSmithKline, Pharmaxis, Prometic, RespiVert, and Roche.

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