GlaxoSmithKline PLC will launch Anoro Ellipta (umeclidinium/vilanterol) in the first quarter. The once-daily long-acting muscarinic antagonist (LAMA) and long-acting beta2-adrenergic agonist (LABA) was approved by FDA for the maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease Dec. 18.

The approval marks the first LAMA/LABA combination product to clear FDA and is a back-to-back win for GSK, which is in the midst of launching Breo Ellipta (fluticasone furoate/vilanterol), the first once-daily inhaled corticosteroid/LABA combination for COPD.

Together, Breo and Anoro are expected to continue the growth within GSK’s important respiratory franchise amid increased competition, including potentially the first generic versions of the blockbuster ICS/LABA AdvairDiskus (fluticasone/salmeterol) Also see "GSK’s Big Push To Maintain Its Respiratory Reign" - In Vivo, 18 November, 2013..

Both products were developed in collaboration with Innoviva Inc. and both are delivered through the novel Ellipta device, a dry powder inhaler that will serve as the new delivery platform for GSK’s respiratory drugs. Umeclidinium is separately pending at FDA as a single agent product, with an April action date.

With the approval of Anoro, GSK beats several rivals to market with a LAMA/LABA combination in the U.S. However, in Europe, Novartis AG holds the first-to-market title with its Ultibro Breezhaler (indacaterol/glycopyrronium), which was approved in Europe in September. Novartis’ U.S. program has been hung up by FDA concerns over dosing and safety, requiring Novartis to initiate a new Phase III trial that is currently ongoing Also see "Novartis Once-Daily COPD Combo Safe, Effective And Ready For Filing – Everywhere But In The U.S." - Pink Sheet, 10 September, 2012..

Boehringer Ingelheim GMBH is also developing a LAMA/LABA using its market-leading LAMA Spiriva (tiotropium) as the LAMA component in combination with the investigational LABA olodaterol. It is in Phase III testing.

The Combination Market For COPD/Asthma
Manufacturer/Brand	Molecules	Mechanism	Delivery	Indication	US Status
GSK’s Advair	Fluticasone/salmeterol	ICS/LABA	DPI/twice daily	COPD/Asthma	Marketed
AstraZeneca’s Symbicort	Budesonide/formoteral fumarate	ICS/LABA	MDI/twice daily	COPD/Asthma	Marketed
Merck & Co.’s Dulera	Mometasone/formoteral fumarate	ICS/LABA	MDI/twice daily	Asthma	Marketed
GSK’s Breo	Fluticasone/vilanterol	ICS/LABA	DPI/once daily	COPD	Marketed
GSK’s Anoro	Vilanterol/umeclidinium	LABA/LAMA	DPI/once daily	COPD	Approved; Phase III for asthma
Novartis’ Ultibro (EU brand name)	Indacaterol/glycopyrronium	LABA/LAMA	DPI/uncertain	COPD	Phase III
Boehringer Ingelheim	Olodaterol/tiotropium (Spiriva)	LABA/LAMA	SMI/once daily	COPD	Phase III
Forest and Almirall	Formoteral/aclidinium	LABA/LAMA	DMI/twice daily	COPD	NDA filing delayed indefinitely
SOURCE: Company filings; Elsevier’s Strategic Transactions

LAMA/LABA combinations could potentially supplant ICS/LABA combinations as the standard of care for COPD, according to some market researchers, given their potential for synergistic efficacy.

“This is great news for patients. It is the first time that patients will be able to take both of these medicines with just one inhaler,” said Elaine Jones, GSK’s medicines development leader for Anoro in an interview. “What you see when you give these to bronchodilators is improved efficacy compared to a single bronchodilator.”

No Post-Marketing CV Study Required

FDA approval of Anoro was widely anticipated after the product received a positive recommendation from FDA’s Pulmonary-Allergy Drugs Advisory Committee, despite panelists concerns about cardiovascular safety and missing data from clinical trials stemming largely from patient drop-outs and lack of follow-up on the part of GSK ([A#14130910008]).

But despite the advisory committee’s concerns about safety and calls for the approval to include a post-marketing requirement to further study the cardiac safety of the product in more severely ill patients, the approval does not include any such commitments.

Jones said the lack of a post approval requirement was not a surprise to GSK following discussions with FDA. “The data with Anoro Ellipta are positive for patients, and we will do our routine monitoring obviously,” she said.

Labeling for Anoro appears largely in line with class labeling for other LABA-containing products when it comes to Warnings, including a black box warning on the risk of asthma-related death. Labeling also includes a Warning not to initiate treatment in acutely deteriorating COPD or to treat acute symptoms. Regarding cardiovascular risks, labeling says, “Anoro Ellipta should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias and hypertension.

The approval was based on the results from a clinical program that enrolled 8,138 patients and included four six-month lung function trials, one 12-month long-term safety study and nine other trials of shorter duration.

Now that Anoro has eased its way through FDA approval, GSK will need to build a case with payers to support reimbursement if the product is to be a commercial success. The company has faced some challenges on the reimbursement front for Breo ([A#00131014008]). Most notably, Express Scripts Holding Co. included Breo and Advair on a list of drugs excluded from coverage on its national formulary in 2014 ([A#00131007006]).

The FDA action is positive news for Theravance too, which has been GSK’s partner since 2002, and is preparing to separate into two publicly traded companies by the end of the year now that Breo is on the market Also see "Theravance Preps For Separation As Breo Hits The U.S. Market" - Pink Sheet, 25 October, 2013.. The San Francisco biotech earlier this year announced plans to create one company, Royalty Management Co., to manage the royalty revenue stream coming from Breo and Anoro, and a second R&D company, Theravance Biopharma.

Theravance stands to receive significant revenue from sales of both products, but the approval of Anoro triggers a $30 million milestone for Theravance to pay to GSK. Another $30 million will be due upon the launch of the product.

With Anoro, GSK Takes A Two-Step Toward Bolstering Respiratory

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