EU approval rec for TIP

Novartis International AG: Novartis receives EU approval recommendation for TOBI® Podhaler®, a fast and simple therapy that helps reduce treatment burden for cystic fibrosis patients

Fri Sep 24, 2010 9:17am EDT


Novartis International AG / Novartis receives EU approval recommendation for TOBI

Podhaler, a fast and simple therapy that helps reduce treatment burden for cystic fibrosis patients processed and transmitted by Hugin AS. The issuer is solely responsible for the content of this announcement.




CHMP supports approval of TOBI Podhaler, a new dry powder form of tobramycin for treating chronic P. aeruginosa lung infection in cystic fibrosis patients over six




Data show new formulation reduces administration time by 72% compared to TOBI, with same

efficacy[1] and using more convenient, patient-friendly device



*



Cystic fibrosis is a life-threatening genetic disease primarily affecting children and young adults - complex daily treatment reduces their ability to lead normal lives



Basel, September 24, 2010 - TOBI® Podhaler® (tobramycin inhalation powder), a fast and

convenient inhaled therapy[1] for use by patients with cystic fibrosis (CF), has been

recommended for approval in the European Union. The Committee for Medicinal Products for

Human Use (CHMP), which reviews medicines for the European Commission, issued a positive

opinion for TOBI Podhaler as a suppressive therapy for chronic Pseudomonas aeruginosa

(Pa) infections in CF patients aged six years and older.



"TOBI Podhaler combines a number of innovations that significantly improve the delivery

of tobramycin, which is an established effective treatment for Pa lung infection in

patients with cystic fibrosis," said Professor Stuart Elborn, Professor of Respiratory

Medicine at Queens' University, Belfast, and President of the European Cystic Fibrosis

Society. "This therapy should help patients to lead more independent lives - an

important factor considering the relatively young age of many people with this disease."



The CHMP based its positive opinion on data showing that TOBI Podhaler provides the same

efficacy[2] as TOBI® (tobramycin solution) with a comparable safety profile[2]. TOBI is

the most widely used inhaled antibiotic for chronic Pa infections in CF[3]. TOBI

Podhaler has a unique dry powder formulation, developed using novel PulmoSphere®

technology to produce particles that are light and porous for deep delivery into the

lung. This means treatment can be given with a portable, patient-friendly device, in

contrast to TOBI which is administered with a nebulizer.



Data show that patients using TOBI Podhaler completed their tobramycin treatment in five

to six minutes instead of 20 minutes with TOBI, a reduction of 72%[1]. Nebulized

treatments require additional time for assembly and disinfection, unlike TOBI Podhaler,

which also does away with the need for refrigeration of the active compound and a power

source for the delivery device. A study found that patients treated with TOBI Podhaler

had significantly higher treatment satisfaction than those treated with TOBI[1].



Due to the complexity of existing anti-Pa treatment, most patients do not fully adhere

to their therapy[4],[5],[6]. In addition, many patients do not clean their nebulizers

properly and these are often contaminated[7],[8],[9],[10]. With TOBI Podhaler, the

inhaler device is disposable and the dry formulation potentially reduces the risk of

bacterial contamination.



"TOBI Podhaler shows how we are applying innovative technologies to better meet the

needs of patients and their families," said David Epstein, Division Head of Novartis

Pharmaceuticals. "TOBI Podhaler also underscores our long-term commitment to improving

the quality of care for patients with diseases such as cystic fibrosis and helping them

to lead longer and more active lives."



Cystic fibrosis (CF) is a life-threatening genetic disease that affects the internal

organs, especially the lungs and digestive system, by clogging them with thick mucus

making it hard to breathe and digest food. A total of 70,000 patients have been

diagnosed with CF worldwide[11]. Symptoms usually develop within the first year of life

and only half of CF patients live to over 35 years of age[12]. In 90% of cases, death is

due to a progressive decline in lung function often made worse by chronic Pseudomonas

aeruginosa infection[13].



The first launch of TOBI came in 1997 and it is now approved in 46 countries including

the US and EU for the treatment of Pseudomonas aeruginosa in CF patients aged six years

old and above.



TOBI Podhaler was submitted for EU approval in December 2009 and is not yet approved in

any country. The European Commission generally follows the recommendations of the CHMP

and is expected to make a decision within three months.

Tobramycin Inhalation Powder (TIP) Improved Lung Function In Cystic Fibrosis (CF) Patients With Respiratory Pseudomonas Aeruginosa (Pa) Infection

Main Category: Cystic Fibrosis
Also Included In: Respiratory / Asthma; Infectious Diseases / Bacteria / Viruses
Article Date: 20 May 2009 - 6:00 PDT

In a Phase III study, TIP, an inhaled investigational formulation of tobramycin, improved lung function (as measured by FEV1) in cystic fibrosis patients with Pseudomonas aeruginosa (Pa) infection, compared to placebo. The data, presented today at the American Thoracic Society (ATS) 2009 International Conference in San Diego, also demonstrated, with respect to secondary endpoints, that TIP decreased sputum Pa density, hospitalization and other antibiotic use in these patients versus placebo.

TIP is currently in Phase III development for the management of CF patients with Pa infection. TIP, a dry-powder form of tobramycin, is delivered in approximately 4 to 6 minutes via a hand-held, portable, pocket-sized inhaler device, twice daily.

More than half of the people with CF have Pa infection, a respiratory condition caused by the Pa bacteria that settle into the thick mucus trapped in the airways. Pa is the most common cause of infection and lung damage in patients with CF.

"The daily treatment routine for patients with CF can take hours. The study findings presented at ATS are promising, as a new treatment option like TIP may allow people with CF an alternative for Pa management," said lead investigator Michael Konstan, MD, Professor and Director, The LeRoy W. Matthews Cystic Fibrosis Center, Rainbow Babies and Children's Hospital and Case Western Reserve University School of Medicine.

In a Phase III placebo-controlled study, patients with CF were administered treatment with TIP 112mg twice daily or matching placebo in a 1:1 ratio during Cycle 1 (28 days on and 28 days off treatment). This was followed by 2 cycles where all patients received TIP1c. The primary efficacy variable was relative change in forced expiratory volume in one second (FEV1) percent predicted from Day 1 to Day 28 (Cycle 1).

At 28 days, patients on TIP showed a significant improvement in FEV1 % predicted with an average improvement of 13% versus placebo (p=.0016). At the end of the first full cycle (Day 56), improvement over placebo in predicted lung function was maintained.

With respect to secondary endpoints, TIP reduced the mean sputum Pa density by 2.59 log10 colony forming units (CFU/mL), compared with 0.24 log10 for placebo. The proportion of patients requiring other antipseudomonal antibiotics was lower with TIP versus placebo (19.6% vs. 32.7%) and the mean duration of additional antipseudomonal antibiotic use was shorter (17 vs. 31.1 days, respectively) over the 56 days of Cycle 1. There were no respiratory-related hospitalizations for patients on TIP compared with 12.2% for patients receiving placebo (average duration of 12.3 days).

Adverse events were reported by 75.5% of placebo-treated and 50% of TIP-treated patients. The most commonly reported adverse events with placebo were cough, lung disorders and productive cough. With TIP, the most common adverse events were cough, lung disorders and sore throat. There were no major changes from baseline in vital signs, hematology, blood chemistry or urine protein. Audiology tests at selected sites indicated that there were no clinically meaningful decreases in hearing thresholds. None of the patients reported adverse events related to hearing.

"Novartis is working closely with respiratory researchers worldwide to develop medications to treat complex respiratory diseases with limited treatment options, including cystic fibrosis," said Robert K. Zeldin, MD, VP and US Medical Franchise Head of Respiratory and Dermatology, Novartis Pharmaceuticals Corporation. "We are pleased to report the findings of the TIP Phase III study, and we look forward to additional clinical data as we work towards regulatory filing."

Source
Novartis Pharmaceuticals Corporation