Q&A: From Practicing Pulmonologist to Researching Treatment Options

Frank Trudo, MD, MBA

Frank Trudo, MD, MBA, was recently appointed as VP, US Respiratory Medical Affairs at AstraZeneca.

You’ve had an interesting career in that you’ve been both a practicing pulmonologist seeing patients every day and a medical expert involved in drug development at AstraZeneca. Take me through your career path and what led you to your current role as VP of US Respiratory, Medical Affairs at AstraZeneca.

I decided to go into pulmonary medicine because I was interested in the multifaceted approach of the specialty across immunology, infectious disease, and oncology. I did my pulmonology specialty training at the University of Pennsylvania and then joined a practice. After 13 years as a practicing pulmonologist, I joined AstraZeneca in 2011 as the Associate Director of Clinical Research, Respiratory and Inflammation. My new role allowed me to pursue my desire to help patients on a different level by guiding the development of medications. Some of the most rewarding parts about working at AstraZeneca are being able to drive the science that helps advance patient care and being at the forefront of advancements in respiratory disease therapies. Over the course of my career, I’ve been involved in numerous projects, including several respiratory clinical trials.

Shifting to a more general treatment landscape question, what do you think is on the horizon for the Inhaled space?

It’s an exciting time in pulmonary medicine. We're recognizing that asthma and COPD are heterogeneous diseases¹, meaning that there’s not just one type of inflammation driving these diseases.

Our aim at AstraZeneca is to transform asthma and COPD treatment through Inhaled combinations at the core of care, precision biologics for the unmet needs of specific patient populations, and scientific advancements in disease modification. Because of the complexity of respiratory disease, we need different treatment and device options for patients. The use of such targeted therapies, on top of controller medication, may lead to better asthma control and less exacerbation risks in patients with asthma.

Switching gears, one of the brands you worked on over the course of your career is SYMBICORT^® (budesonide/formoterol fumarate dihydrate) Inhalation Aerosol. Can you tell us about this treatment option?

Combination products that contain an inhaled corticosteroid (ICS) and a long-acting beta₂ adrenergic agonist (LABA), including SYMBICORT, are important medications for many patients^2,3 and are a mainstay of inhalational therapy for asthma and COPD. AstraZeneca’s investment to fully explore indications in different populations shows our continued commitment to the respiratory space.

SYMBICORT is indicated for the treatment of asthma in patients 6 years of age and older.⁴ SYMBICORT should be used for patients not adequately controlled on a long-term asthma-control medication such as an ICS or whose disease warrants initiation of treatment with both an ICS and LABA.⁴

SYMBICORT 160/4.5 µg is indicated for the maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema, and to reduce COPD exacerbations.⁴

SYMBICORT is not indicated for the relief of acute bronchospasm.⁴

What are some milestones that speak to SYMBICORT’s evolution over the past several years?

Last year was an important year of milestones for SYMBICORT because the FDA approved three label updates, made possible through several clinical trials. These included a safety/efficacy pediatric asthma indication trial in patients 6 to <12 years of age, a Phase 3b trial designed to support approval of the COPD exacerbation indication, which I helped design and execute, and a LABA post marketing safety study in asthma patients ≥12 years of age, which was part of an FDA-required class-wide clinical trial program conducted by manufacturers of ICS/LABAs that evaluated the risk of serious asthma-related events with ICS/LABA versus ICS alone.

In January 2017, SYMBICORT 80/4.5 µg was approved for the treatment of asthma in patients aged six up to 12 years. SYMBICORT 80/4.5 µg and 160/4.5 µg were already approved in the US to treat asthma in patients 12 years and older.⁵

In September 2017, SYMBICORT 160/4.5 µg was approved for reducing exacerbations in patients with COPD. This added to the previously approved indication of maintenance treatment of airflow obstruction in patients with COPD including chronic bronchitis and/or emphysema.⁵

In December 2017, the US Food and Drug Administration (FDA) approved updates to the labeling for all ICS/LABA products, including SYMBICORT. These updates included removal of the Boxed WARNING for serious asthma-related outcomes.⁵ The ICS/LABA labels all retain a Warning and Precaution related to an increased risk of asthma-related death when LABAs are used without an ICS in the treatment of asthma.⁵ These label updates were a result of an FDA review of 4 post-marketing LABA safety studies conducted with ICS/LABA products, including the study with SYMBICORT.⁵

IMPORTANT SAFETY INFORMATION FOR SYMBICORT

• Use of long-acting beta₂-adrenergic agonists (LABA) as monotherapy (without inhaled corticosteroids [ICS]) for asthma is associated with an increased risk of asthma-related death. Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. These findings are considered a class effect of LABA. When LABA are used in fixed dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared to ICS alone
• SYMBICORT is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms
• SYMBICORT should not be initiated in patients during rapidly deteriorating episodes of asthma or COPD
• Patients who are receiving SYMBICORT should not use additional formoterol or other LABA for any reason
• Localized infections of the mouth and pharynx with Candida albicans has occurred in patients treated with SYMBICORT. Patients should rinse the mouth after inhalation of SYMBICORT
• Lower respiratory tract infections, including pneumonia, have been reported following the administration of ICS
• Due to possible immunosuppression, potential worsening of infections could occur. A more serious or even fatal course of chickenpox or measles can occur in susceptible patients
• It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression may occur, particularly at higher doses. Particular care is needed for patients who are transferred from systemically active corticosteroids to ICS. Deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available ICS
• Caution should be exercised when considering administration of SYMBICORT in patients on long-term ketoconazole and other known potent CYP3A4 inhibitors
• As with other inhaled medications, paradoxical bronchospasm may occur with SYMBICORT
• Immediate hypersensitivity reactions may occur, as demonstrated by cases of urticaria, angioedema, rash, and bronchospasm
• Excessive beta-adrenergic stimulation has been associated with central nervous system and cardiovascular effects. SYMBICORT should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension
• Long-term use of ICS may result in a decrease in bone mineral density (BMD). Since patients with COPD often have multiple risk factors for reduced BMD, assessment of BMD is recommended prior to initiating SYMBICORT and periodically thereafter
• ICS may result in a reduction in growth velocity when administered to pediatric patients
• Glaucoma, increased intraocular pressure, and cataracts have been reported following the administration of ICS, including budesonide, a component of SYMBICORT. Close monitoring is warranted in patients with a change in vision or history of increased intraocular pressure, glaucoma, or cataracts
• In rare cases, patients on ICS may present with systemic eosinophilic conditions
• SYMBICORT should be used with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines
• Beta-adrenergic agonist medications may produce hypokalemia and hyperglycemia in some patients
• The most common adverse reactions ≥3% reported in asthma clinical trials included nasopharyngitis, headache, upper respiratory tract infection, pharyngolaryngeal pain, sinusitis, pharyngitis, rhinitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis
• The most common adverse reactions ≥3% reported in COPD clinical trials included nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection
• SYMBICORT should be administered with caution to patients being treated with MAO inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents
• Beta-blockers may not only block the pulmonary effect of beta-agonists, such as formoterol, but may produce severe bronchospasm in patients with asthma
• ECG changes and/or hypokalemia associated with nonpotassium-sparing diuretics may worsen with concomitant beta-agonists. Use caution with the coadministration of SYMBICORT

INDICATIONS

SYMBICORT is indicated for the treatment of asthma in patients 6 years and older not adequately controlled on a long-term asthma-control medication such as an ICS or whose disease warrants initiation of treatment with both an ICS and LABA. (also see DOSAGE AND ADMINISTRATION).

SYMBICORT 160/4.5 is indicated for the maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema, and to reduce COPD exacerbations.

SYMBICORT is NOT indicated for the relief of acute bronchospasm.

Please see full Prescribing Information, including Patient Information.

References:

1. Heaney LG, McGarvey LP. Personalized medicine for asthma and chronic obstructive pulmonary disease. Respiration. 2017;93:153—161.
2. Global Initiative for Asthma. Global strategy for asthma management and prevention: 2018 report. https://ginasthma.org/2018-gina-report-global-strategy-for-asthma-management-and-prevention/. Accessed June 28, 2018.
3. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2018 report. https://goldcopd.org/gold-reports/. Accessed June 28, 2018.
4. SYMBICORT [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; December 2017.
5. AstraZeneca Pharmaceuticals LP. US FDA updates SYMBICORT label with LABA safety class revisions and removes Boxed WARNING for serious asthma-related outcomes [press release]. https://www.astrazeneca-us.com/content/az-us/media/press-releases/2017/us-fda-updates-symbicort-label-with-laba-safety-class-revisions-and-removes-boxed-warning-for-serious-asthma-related-outcomes-12212017.html. Published December 21, 2017. Accessed June 28, 2018