Novartis data at ECFS

Data presented today at the European Cystic Fibrosis Society (ECFS) Conference in Valencia demonstrate that TIPTM* (tobramycin inhalation powder) is as effective as the current standard of care, tobramycin inhalation solution (TOBI®), in treating Pseudomonas aeruginosa (Pa) infection in patients with cystic fibrosis (CF)². The data also show that TIP significantly reduces the time it takes for patients to administer treatment by 72% (mean duration for TIP was 14.1 min less than TOBI, p<0.0001), allowing for greater treatment satisfaction and convenience¹.

The randomized, Phase III study designed to assess the efficacy and safety of TIP compared to TOBI in patients with CF showed no significant difference in the change in FEV1 from baseline to the end of Cycle 3 of the study between the two treatment groups (LS (least squares) mean difference: 1.1% [85% one-sided CI -0.67, 2.96])2. The mean change from baseline of sputum density was greater in the TIP vs TOBI group on Day 28 of Cycle 3 (mean change in log10CFU/g: –1.6 vs –0.92 for mucoid biotype and –1.77 vs –0.73 for dry biotype, respectively). The proportion of patients experiencing serious adverse events was similar across both groups. With respect to non-serious adverse events, cough and dysphonia were reported more frequently with TIP than with TOBI.

Treatment convenience and satisfaction with TIP was compared to TOBI using a patient-reported Treatment Satisfaction Questionnaire for Medication (TSQM). Results demonstrated that TIP significantly shortened treatment administration time compared to TOBI (mean 5.6 min vs 19.7 min, p<0.0001)1. This decrease in time did not take into account the additional time saved on device assembly and caretaking, both of which were rated by patients as significantly more convenient with TIP (p<0.0001)1. Over the course of the study, patients reported significantly greater global satisfaction for TIP compared with TOBI (p<0.0018)1. Self assessed patient ratings of the impact of treatment side effects showed no difference between TIP and TOBI (p=0.6833)1.

TIP, a dry powder formulation of tobramycin delivered twice daily via a hand-held, portable, pocket-sized device, has been developed to shorten administration time and enhance treatment convenience; both factors in easing the current treatment burden experienced by CF patients1,2.

“These new data comparing tobramycin dry powder with tobramycin solution administered via a nebulizer, showing the same efficacy as TOBI, but with a better treatment convenience and patients’ satisfaction, are promising. With a daily treatment routine taking hours for CF patients, it is important that alternative treatment options be developed that can reduce administration time and thus alleviate the treatment burden for our patients,” 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.

“Novartis welcomes these findings as there is a real unmet need in this vulnerable group of patients for new treatment options. Today’s data build on earlier Phase III results presented in 2009 and further demonstrates the potential TIP may provide as a new treatment approach for CF patients.’’ said David Morris, MD, Global Head of Development, Respiratory Franchise, Novartis. ‘’Novartis is committed to researching and developing effective therapies for serious diseases with limited treatment options such as cystic fibrosis and these latest data further reinforce this approach,’’ he added.

TIP (tobramycin inhalation powder) is not approved in any country and was submitted for EU regulatory approval in December 2009.

*The name “TIP” is used by Novartis to describe its investigational tobramycin inhalation powder.

About CF

Cystic fibrosis (CF) is a common, life-threatening genetic disease, primarily affecting the respiratory and digestive systems in children and young adults. CF causes the production of thick, sticky mucus that clogs the air passages of the lungs, leading to persistent infection and permanent lung damage due to scarring3. The main symptoms of CF are a persistent cough, often with phlegm, frequent lung infections (e.g. pneumonia or bronchitis), wheezing and shortness of breath5. More than half of the people with CF have Pseudomonas aeruginosa (Pa) infection, a respiratory condition caused by the Pa bacteria that settle into the thick mucus trapped in the airways6.

Genetic screening can identify carriers of the mutant gene, and a simple sweat test is used to diagnose CF patients3,5. There are at present no treatments to correct the underlying genetic defect, and therefore current therapy aims to improve quality of life by alleviating symptoms and slowing disease progression3.

Individuals with CF have an average lifespan of approximately 30 years, however, as a result of advances in research and treatments5, survival rates are improving and the projected life-span for babies born with CF in the 1990s is now around 40 years3.

Prevalence of CF varies among ethnic groups, with Caucasians of Northern European origin having the highest incidence. International prevalence ranges from 1 case per 620 in a confined population with Dutch ancestry to 1 case per 90,000 in Asians7. It is estimated that there are between 70,000 and 100,000 people living with CF worldwide4,5.

About TOBI^®8

TOBI® (tobramycin inhalation solution) is an inhaled antibiotic indicated in most EU countries for the long-term management of chronic Pseudomonas aeruginosa (Pa) in patients aged 6 years and older with cystic fibrosis (CF).

TOBI has a proven efficacy and safety profile established through two double-blind, randomized, placebo-controlled, parallel group, 24-week clinical studies. Patients in the TOBI-arms of these trials had reduced length of hospital stay, reduced need for parenteral antibiotics, decreased density of Pa in the sputum and improved lung function8.

Safety and efficacy of TOBI have not been demonstrated in patients under the age of 6 years, patients with FEV1 <25% or >75% predicted, or patients colonized with Burkholderia cepacia. Patients who are allergic to the aminoglycoside class of antibiotics should not take TOBI. Pregnant women and nursing mothers should consult with their doctors before taking TOBI8.

TOBI is taken in doses of 300mg twice a day in a 28-day-on/28-day-off cycle and is delivered via the PARI LC® PLUS Reusable Nebulizer and a suitable compressor so that it directly reaches the infected areas in the lungs. No dose titration is needed for differences in weight or age8.

References

1. Geller DE, Flume PA, Brockhaus F et al. Treatment convenience and satisfaction of tobramycin inhalation powder (TIPTM) versus TOBI® in cystic fibrosis (CF) patients. Poster and abstract presented at 33rd European Cystic Fibrosis Congress 17 June 2010
2. Konstan MW, Flume PA, Brockhaus F. Safety and efficacy of tobramycin inhalation powder (TIPTM) in treating cystic fibrosis patients infected with Pseudomonas aeruginosa (Pa). Poster and abstract presented at 33rd European Cystic Fibrosis Congress 17 June 2010
3. The European Lung Foundation: Cystic Fibrosis: http://www.european-lung-foundation.org/index.php?id=30 Last accessed June 2010
4. Cystic Fibrosis Worldwide: What is Cystic Fibrosis? : http://www.cfww.org/about/article/400/What_is_Cystic_Fibrosis Last accessed June 2010
5. The Cystic Fibrosis Foundation: About Cystic Fibrosis http://www.european-lung-foundation.org/index.php?id=30 Last accessed June 2010
6. About.com: cystic fibrosis http://cysticfibrosis.about.com/od/relateddiseases/a/paeruginosa.htm Last accessed June 2010
7. Sharma, GD. Cystic Fibrosis. eMedecine Medscape: http://emedicine.medscape.com/article/1001602-overview Last accessed June 2010
8. TOBI® (Tobramycin Inhalation Solution, USP) Prescribing information: Novartis Pharmaceuticals Corporation November 2009