DALIRESP receives US FDA approval for 250 mcg starting dose for patients with severe COPD

Study shows DALIRESP 250 mcg as a starting dose for the first four weeks followed by 500 mcg thereafter, demonstrated a 25% reduction in the percentage of patients discontinuing treatment compared to DALIRESP 500 mcg for 12 weeks

AstraZeneca today announced the U.S. Food and Drug Administration (FDA) has approved DALIRESP® (roflumilast) 250 mcg as a starting dose once daily for the first 4 weeks of treatment followed by 500 mcg thereafter to help reduce the rate of treatment discontinuation in some patients. DALIRESP is currently indicated for reducing the risk of chronic obstructive pulmonary disease (COPD) exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations.

DALIRESP is not a bronchodilator and is not indicated for the relief of acute bronchospasm.  DALIRESP 250 mcg is a starting dose, for the first 4 weeks of treatment only and is not the effective (therapeutic) dose.

Tosh Butt, Vice President, Respiratory, AstraZeneca, said: “As the only once-daily tablet to provide enhanced protection against COPD exacerbations when added to current bronchodilator therapy, this is an important new dosing option to help patients start and stay on treatment. Exacerbations are associated with hospitalizations and an accelerated decline in lung function, and these patients living with COPD need effective treatment options.”

The 250 mcg dose approval was based on data from the Evaluation of Tolerability and Pharmacokinetics of Roflumilast, 250 mcg and 500 mcg, as add-on to Standard COPD Treatment to Treat Severe COPD (OPTIMIZE) study.

Over the 12-week study period, the percentage of patients discontinuing treatment was significantly lower in patients who initially received DALIRESP 250 mcg daily for 4 weeks followed by DALIRESP 500 mcg daily for 8 weeks (18.4%) compared to those who received DALIRESP 500 mcg once a day for 12 weeks (24.6%) (Odds Ratio = 0.66; 95% CI: 0.47 to 0.93; p=0.017). Because this trial was limited to 12 weeks in duration, whether initiation of dosing with DALIRESP 250 mcg improves the long-term tolerability of DALIRESP 500 mcg has not been determined.

In 8 controlled clinical trials, the most common adverse reactions (≥2% and greater than placebo) were diarrhea (9.5% vs 2.7%), weight loss (7.5% vs 2.1%), nausea (4.7% vs 1.4%), headache (4.4% vs 2.1%), back pain (3.2% vs 2.2%), influenza (2.8% vs 2.7%), insomnia (2.4% vs 1.0%), dizziness (2.1% vs 1.1%), and decreased appetite (2.1% vs 0.4%).

INDICATION AND USAGE

DALIRESP® (roflumilast) is indicated as a treatment to reduce the risk of chronic obstructive pulmonary disease (COPD) exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations.

Limitations of Use

  • DALIRESP is not a bronchodilator and is not indicated for the relief of acute bronchospasm.
  • DALIRESP 250 mcg is a starting dose for the first 4 weeks of treatment only and is not the effective (therapeutic) dose

IMPORTANT SAFETY INFORMATION

Contraindications

DALIRESP® (roflumilast) is contraindicated in patients with moderate to severe liver impairment (Child-Pugh B or C).

Warnings and Precautions

  • DALIRESP is not a bronchodilator and should not be used for the relief of acute bronchospasm
  • Prescribers should advise patients, their caregivers, and families to be alert for the emergence or worsening of insomnia, anxiety, depression, suicidal thoughts or other mood changes, and if such changes occur, to contact their healthcare provider. Prescribers should carefully evaluate the risks and benefits of continuing treatment if such events occur. Before using DALIRESP in patients with a history of depression and/or suicidal thoughts or behavior, prescribers should carefully weigh the risks and benefits of treatment with DALIRESP
  •     Treatment with DALIRESP is associated with an increase in psychiatric adverse reactions. In 8 controlled clinical trials 5.9% of patients treated with DALIRESP reported psychiatric adverse reactions vs 3.3% treated with placebo. The most common psychiatric adverse reactions in these studies were insomnia (2.4% vs 1.0%), anxiety (1.4% vs 0.9%), and depression (1.2% vs 0.9%). Three patients treated with DALIRESP experienced suicide-related adverse reactions (one completed suicide and two suicide attempts) compared to one patient (suicidal ideation) treated with placebo. In an additional placebo-controlled 1-year clinical trial (Trial 9), which assessed the effect of DALIRESP when added to a fixed-dose combination of an inhaled corticosteroid and long-acting beta agonist, one patient completed suicide while receiving DALIRESP
  • Patients should have their weight monitored regularly. If unexplained or clinically significant weight loss occurs, weight loss should be evaluated and treatment discontinuation considered
  •     In addition to weight loss being reported as a common adverse reaction (7.5% of patients treated with DALIRESP vs 2.1% placebo), weight was prospectively assessed in two 1- year pivotal clinical trials. In these studies that compared DALIRESP to placebo, 20% vs 7% experienced moderate weight loss (5-10% of bod y weight) and 7% vs 2% experienced severe weight loss (>10% body weight). During the follow-up period after discontinuing DALIRESP, the majority of patients regained some of the weight they had lost
  • Use with strong cytochrome P450 enzyme inducers (eg, rifampicin, phenobarbital, carbamazepine, phenytoin) is not recommended, as they decrease the exposure and m ay reduce the therapeutic effectiveness of DALIRESP

Adverse Reactions

In 8 controlled clinical trials, the most common adverse reactions (≥2% and greater than placebo) were diarrhea (9.5% vs 2.7%), weight loss (7.5% vs 2.1%), nausea (4.7% vs 1.4%), headache (4.4% vs 2.1%), back pain (3.2% vs 2.2%), influenza (2.8% vs 2.7%), insomnia (2.4% vs 1.0%), dizziness (2.1% vs 1.1%), and decreased appetite (2.1% vs 0.4%). The safety profile of DALIRESP in Trial 9 was consistent with the key pivotal studies.  

Please read full Prescribing Information, including Medication Guide.

NOTES TO EDITORS

About OPTIMIZE
The tolerability of DALIRESP was evaluated in a 12-week randomized, double-blind, parallel group trial in patients with severe COPD associated with chronic bronchitis (Trial 10). At screening, patients were required to have had at least one exacerbation in the previous year. A total of 1,323 patients were randomized to receive DALIRESP 500 mcg once a day for 12 weeks (n=443), DALIRESP 500 mcg every other day for 4 weeks followed by DALIRESP 500 mcg once a day for 8 weeks (n=439), or DALIRESP 250 mcg once a day for 4 weeks followed by DALIRESP 500 mcg once a day for 8 weeks (n=441).

About COPD
COPD is a progressive disease associated mainly with tobacco smoking, air pollution or occupational exposure, which can cause obstruction of airflow in the lungs making it hard to breathe. In the United States, COPD is the third leading cause of death. Its prevalence in adults 18 years of age and older is 6.5 percent. An estimated 16 million people are currently diagnosed with COPD, and millions more are believed to have it but do not know it.

About DALIRESP
DALIRESP is a selective phosphodiesterase-4 inhibitor indicated as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. DALIRESP is not a bronchodilator and is not indicated for the relief of acute bronchospasm.  DALIRESP 250 mcg is a starting dose for the first 4 weeks of treatment only and is not the effective (therapeutic) dose.

About AstraZeneca in Respiratory Disease
Respiratory disease is one of AstraZeneca’s main therapy areas, and the Company has a growing portfolio of medicines that reached more than 18 million patients in 2016. AstraZeneca’s aim is to transform asthma and COPD treatment through inhaled combinations at the core of care, biologics for the unmet needs of specific patient populations, and scientific advancements in disease modification.

The Company is building on a 40-year heritage in respiratory disease and AstraZeneca’s capability in inhalation technology spans both pMDIs and dry powder inhalers. AstraZeneca’s research is focused on addressing underlying disease drivers focusing on the lung epithelium, lung immunity and lung regeneration.

About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas – Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

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US-17684 Last Updated 1/18