Boehringer Ingelheim Pharmaceuticals Inc. is acting preemptively to block potential generic or follow-on versions of its chronic obstructive pulmonary disease (COPD) treatment Spiriva HandiHaler (tiotropium bromide inhalation powder), with a citizen petition that echoes a similar one filed by GlaxoSmithKline PLC for its asthma and COPD treatment Advair.

As of Oct. 13, the date of Boehringer Ingelheim’s petition, the company said it was aware of no applications actually pending; the first of the patents on the product expires Dec. 26. In that, BI’s petition resembles GSK’s effort related to Advair (fluticasone propionate and salmeterol), which lost exclusivity in 2010 but does not yet have a generic challenger.

GSK too acted preemptively, filing a citizen petition in December 2009 to impose conditions on generic inhalation products containing either or both of the active ingredients in Advair. FDA has not yet responded to that petition, but Boehringer Ingelheim says it “endorses the actions requested of FDA in that petition as and to the extent they apply to all orally inhaled drug products,” including Boehringer Ingelheim’s. The law firm Ropes & Gray drew up both petitions.

GSK asked that FDA require generics to conform to the reference-listed drug (RLD) in patient instructions and qualitative/quantitative formulation sameness standards, and that they be clinically tested in both pediatric and adult patients and in both asthma and COPD patients. Mylan NV and Teva Pharmaceutical Industries Ltd. appear to be preparing to file ANDAs for generic Advair (Also see "Mylan Exudes Confidence About Plan For Biogenerics" - Pink Sheet, 22 February, 2012. and Also see "Teva Launches Generic Salmeterol in the U.K. To Compete With GSK's Serevent" - Pink Sheet, 7 October, 2011.).

Similarly, Boehringer Ingelheim asked FDA to set strict conditions on applications for approval of generics and follow-on 505(b)(2) products. The firm asks FDA to require any generic formulation of its tiotropium products to comply with the prevailing qualitative/quantitative sameness standards. For 505(b)(2) follow-ons, the company said FDA should require “a robust clinical program, including clinical studies, that fully addresses all safety and efficacy issues which may arise/appear as a result of any changes or differences in a follow-on product … for all indications without extrapolation of the conclusions from one indication to another.”

Devices Must “Not Change The Operating Mechanics”

Additionally, the company is asking FDA to require generic firms to demonstrate bioequivalence by “developing well-defined protocols with established endpoints for comparative clinical studies; developing and validating in vitro-in vivo correlations; [and] establishing statistically justified criteria for declaring bioequivalence.”

Moreover, Boehringer Ingelheim argues that any generic must have the same labeling and instructions for use as the RLD, and that if there are any differences in the generic inhaler device’s design, operating principles or ergonomics, that these must “not change the operating mechanics for the patient, which would compromise the interchangeability of the generic and RLD products in the patient's hands.”

For follow-ons, the company argues that “the science in this regard is still nascent, and new approaches and methodologies will be necessary before any proposed DPI [dry powder inhaler] containing tiotropium bromide can be determined to be bioequivalent to Spiriva.”

In 2011, Spiriva sales totaled €3.153 billion ($4.038 billion), nearly one-quarter of Boehringer Ingelheim’s total net sales of €13.171 billion ($16.868 billion).

As Boehringer Ingelheim plays preemptive defense on Spiriva generics, the firm is also moving to extend its asthma franchise, with novel long-acting beta-agonist olodaterol slated to go before FDA’s Pulmonary-Allergy Drugs Advisory Committee on Jan. 29 for a chronic obstructive pulmonary disease claim Also see "Boehringer’s Olodaterol Will Have To Pass LABA Hurdles At January Advisory Committee" - Pink Sheet, 19 November, 2012..

Boehringer Ingelheim’s Me-Too Petition Against Generic Spiriva

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