Anticholinergic inhalers

[chantell.reagan]

We received the following question from one of our members:

"What about Combivent and Spiriva? Do you have information on those?"

[chantell.reagan]

Please note that there is very limited generic presence in this class primarily because of the challenges in demonstrating bioequivalence for oral inhaled anticholinergics. In order to demonstrate bioequivalence, generic anticholinergics must demonstrate reversibility, which is necessary to obtain a dose-response relationship. Additionally there are "unresolved issues in the design of bioequivalence study", which include "identification of a subgroup of COPD responders, improved understanding of the dose-response characteristics of anticholinergic bronchodilators, selection of doses for the study, and type of systemic exposure study for poorly absorbed drugs in the study designs must pass all of the following tests: in vitro testing for device performance, pharmacodynamic studies of lung function for local delivery, and pharmacokinetic studies for systemic exposure." In addition, the study design must take into account each component of combination drugs when determining bioequivalence. It appears that the FDA and the industry are still engaged in a dialogue focused on the improvement of these requirements but no final changes in FDA standards have been proposed yet. (Sources: FDA: Critical Path Opportunities for Generic Drugs (5/07))

Combivent

First generic approval/launch forecast:

o Expected by 6/2015

Background, details, and sources:

o All currently listed patents expire by 6/9/2015 (Sources: FDA’s Orange Book)
o No ANDAs with Paragraph IV certification have been submitted. (Sources: FDA paragraph IV list)
o As of 1/10, the FDA has not yet issued any approvals for generic equivalents. (Sources: Drugs@FDA)

Spiriva

First generic approval/launch forecast:

o Expected by 3/2023

Background, details, and sources:

o All currently listed patents expire by 3/10/2023 (Sources: FDA’s Orange Book)
o No ANDAs with Paragraph IV certification have been submitted. (Sources: FDA paragraph IV list)
o As of 1/10, the FDA has not yet issued any approvals for generic equivalents. (Sources: Drugs@FDA)

[diana.papshev]

We received feedback that this information is especially relevant considering recent AHRQ announcement "that articulated that Spiriva had superior mortality data over theophylline."

For more information, see the following AHRQ reports:
1. Outcomes Associated with Tiotropium Use in Chronic Obstructive Pulmonary Disease Patients
2. Mortality Risk in Chronic Obstructive Pulmonary Disease Patients Using Theophylline