Will Theravance's Vibativ Get A Breath Of Fresh Air?

Theravance 111912

Nosocomial pneumonia, also known as hospital-acquired pneumonia, is an infection of the lungs that occurs during a hospital stay, and is caused by gram-positive bacteria such as methicillin-resistant Staphylococcus aureus, or MRSA. Linezolid and Vancomycin are the most common recommended medications for methicillin-resistant Staphylococcus aureus hospital-acquired pneumonia.

At the altar awaiting the recommendation of an FDA panel of outside experts for nosocomial pneumonia after a long and frustrating journey is Vibativ, discovered by Theravance Inc. (THRX).

Vibativ was approved by the FDA for the treatment of complicated skin and skin structure infections (cSSSI) caused by susceptible gram-positive bacteria in adult patients in September 2009.

A new drug application for Vibativ seeking approval in the indication of nosocomial pneumonia, or NP, based on two phase III studies which met their primary efficacy endpoint of clinical cure was submitted by Theravance in January 2009. But the following year - in 2010, a new draft guidance with a focus on mortality as the primary efficacy endpoint for antibacterial clinical trial design for the treatment of nosocomial pneumonia was issued by the regulatory agency.

Since the phase III studies of Vibativ in the indication of nosocomial pneumonia did not meet the new draft guidance, the company was issued a Complete Response Letter in late 2010 and was asked to conduct additional clinical studies in order for the drug to be approved for NP.

Though the company did not conduct additional clinical studies for NP, it has been in discussions with the FDA concerning the Vibativ NDA for nosocomial pneumonia.

In September of this year, Theravance was notified that its Vibativ NDA for nosocomial pneumonia will be reviewed by the FDA's Anti-Infective Drugs Advisory Committee on November 29, 2012.

Theravance and Japan-based Astellas Pharma Inc. had a global collaboration arrangement for the development and commercialization of Vibativ that was signed in 2005. This agreement was terminated in January of this year and Theravance regained full global rights to Vibativ.

In March of 2012, Theravance entered into a series of purchase agreements with Astellas for the purchase of Vibativ active pharmaceutical ingredient and other raw materials.

Vibativ won the EU approval for nosocomial pneumonia caused by MRSA last September. However, in May 2012, the European Commission suspended the marketing authorization because the third party drug product supplier did not meet the Good Manufacturing Practice requirements for the manufacture of Vibativ.

Vibativ is currently subject to critical product shortages and regional supply outages in the U.S. due to manufacturing issues at the single-source supplier of Vibativ. Theravance has been evaluating global commercialization alternatives for Vibativ either alone or with partners.

Will Vibativ pass muster with the FDA panel for the proposed treatment of nosocomial pneumonia this time?

Another drug candidate from the respiratory franchise of Theravance, which is under FDA review is FF/VI, previously referred to as Relovair, for patients with chronic obstructive pulmonary disease, partnered with GlaxoSmithKline plc (GSK). FF/VI is a drug combining fluticasone furoate, an inhaled corticosteroid and Vilanterol. The FDA decision date for FF/VI is set for May 12, 2013.

The Marketing Authorisation Application for FF/VI for COPD (chronic obstructive pulmonary disease) and asthma has been validated by the European Medicines Agency.

FF/VI is expected to be a follow-up to the biggest selling drug for COPD, namely GlaxoSmithKline's Seretide/Advair.

Umeclidinium bromide/Vilanterol, or UMEC/VI, GSK961081 and TD-4208 are the other development programs under the company's respiratory franchise that is partnered with GlaxoSmithKline.

GSK961081 has successfully completed a phase IIb study in chronic obstructive pulmonary disease COPD while global regulatory submissions for UMEC/VI in COPD are expected to commence from the end of this year. TD-4208 for COPD is under phase II development.

Also in the pipeline are:

* TD-1211 for opioid-induced constipation. In July of this year, Theravance announced positive topline results from a phase 2b study evaluating TD-1211 as a potential treatment for chronic, non-cancer pain patients with opioid-induced constipation.

* TD-9855, which is under phase II study for Attention-Deficit/Hyperactivity Disorder. The company plans to initiate a phase II study with TD-9855 in patients with fibromyalgia in the next few months.

* TD-1792, which successfully completed phase II studies in complicated skin and skin structure infections in 2007. Last month, Theravance entered into an agreement with R-Pharm for the development and commercialization of TD-1792.

* Velusetrag (TD-5108), a highly selective 5-HT 4 receptor agonist that has successfully completed a phase II proof-of-concept study in chronic idiopathic constipation. In October 2012, Theravance and Alfa Wassermann S.p.A. entered into a development and commercialization agreement for Velusetrag.

A quick look at Theravance's balance sheet...

The company's first approved product, Vibativ, was launched in the U.S. in November 2009, and to date has generated only modest revenues. As of September 30, 2012, the company had an accumulated deficit of approximately $1.3 billion.

Net loss for Q3, 2012 was $34.7 million or $0.37 per share on revenue of $1.4 million. This compares with a net loss of $30.63 million or $0.37 per share and revenue of $6.43 million.

The company ended September 30, 2012 with $362.4 million in cash, cash equivalents, and marketable securities.

THRX has thus far hit a 52-week low of $12.91 and a 52-week high of $31.87. The stock, which has shed nearly 23% over the last three months, closed Friday's trading at $20.21.

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