Press Release: Novartis announces positive results from Phase III PALLADIUM study of inhaled combination QMF149 in patients with uncontrolled asthma

-- Once-daily QMF149 demonstrated superior improvement in lung function

versus mometasone furoate, meeting primary endpoint[1]

-- PALLADIUM is part of Phase III PLATINUM clinical development program,

which evaluates inhaled combinations QMF149 and QVM149

-- Novartis is aiming to reimagine inhaled asthma care by developing

once-daily fixed-dose combination treatments to help patients achieve

better asthma control

Basel, September 30, 2019 -- Novartis today announced that

investigational, once-daily, fixed-dose inhaled QMF149 (indacaterol

acetate and mometasone furoate or IND/MF) was superior to mometasone

furoate (MF) in improving trough forced expiratory volume in one second

(FEV(1) ) after 26 weeks, meeting the primary endpoint of the Phase III

PALLADIUM clinical trial. This superior improvement in lung function was

achieved in patients with asthma who remain uncontrolled on treatment

with inhaled corticosteroid (ICS) at medium or high dose, or long-acting

beta agonist (LABA)/ICS at low dose. IND/MF was generally well tolerated,

and safety was comparable across treatment arms[1].

The key secondary endpoint, improvement in Asthma Control Questionnaire

(ACQ-7), was also met for combined doses of IND/MF when compared to

combined doses of MF, with a statistically significant improvement of

asthma control achieved from baseline at Week 26[1]. The PALLADIUM study

was conducted to evaluate the efficacy and safety of medium and high

doses of QMF149 (150/160 ug and 150/320 ug) delivered via the

dose-confirming Breezhaler(R) device versus two respective medium and

high doses of MF (400 ug and 800 ug) delivered via Twisthaler(R) in

patients with asthma who were uncontrolled on medium or high dose ICS or

low dose LABA/ICS (as determined by pulmonary function testing and

effects on asthma control). The PALLADIUM study also included an

additional secondary comparison of high dose IND/MF delivered via the

dose-confirming Breezhaler(R) device with twice daily salmeterol

xinafoate/fluticasone propionate (50/500 ug) delivered via the

Accuhaler(R) [2].

"Nearly half of all patients with moderate-to-severe asthma remain

uncontrolled and continue to suffer with regular symptoms and

exacerbations," said Dr. Richard van Zyl-Smit, Associate Professor, Head

of the Lung Clinical Research Unit, University of Cape Town Lung

Institute, and Consultant Pulmonologist, Groote Schuur Hospital, Cape

Town, South Africa. "Promising results from PALLADIUM in both doses of

the indacaterol and mometasone furoate combination provide evidence for

the efficacy and safety profile of QMF149 for the treatment of asthma.

If approved, the easy-to-use, dose-confirming, once-daily device adds an

additional and important option for clinicians treating asthma. I

believe that this new fixed-dose combination has the potential to

improve and simplify the lives of many patients with uncontrolled

asthma."

"We are very pleased that PALLADIUM demonstrated the efficacy and safety

of medium and high doses of QMF149, delivered via our dose-confirming

Breezhaler(R) device," said Linda Armstrong, MD, Respiratory Development

Unit Head, Novartis Pharmaceuticals. "These results complement the

findings of the Phase III QUARTZ study for a lower dose of QMF149 and

provide additional evidence of the benefits of this combination

treatment across the full dose range. We look forward to announcing more

data from the PLATINUM clinical development program."

The overall incidence of adverse events (AEs) and serious AEs in

PALLADIUM was comparable among treatment groups and consistent with the

known safety profile of the monocomponents[1].

The detailed results from the PALLADIUM trial will be presented at

upcoming medical congresses.

As previously announced, the regulatory submission for QMF149 was

accepted for review by the European Medicines Agency earlier this year.

About QMF149 (indacaterol acetate and mometasone furoate)

The combination of indacaterol acetate and mometasone furoate (IND/MF)

is currently in development for the treatment of patients with

uncontrolled asthma (whose lives remain impacted by asthma despite

current treatment) and the regulatory submission of this investigational

once-daily inhaled combination treatment has recently been accepted for

review by the European Medicines Agency (EMA). It combines the

bronchodilation of the ultra-LABA indacaterol acetate (a long-acting

beta agonist [LABA]) with the anti-inflammatory mometasone furoate (an

ICS) in a precise once-daily formulation, delivered via the

dose-confirming Breezhaler(R) device. Mometasone furoate is exclusively

licensed to Novartis from a subsidiary of Merck & Co., Inc., Kenilworth,

NJ, USA, for use in QMF149.

About QVM149 (indacaterol acetate, glycopyrronium bromide and mometasone

furoate)

The combination of indacaterol acetate, glycopyrronium bromide and

mometasone furoate (IND/GLY/MF) is currently in development for the

treatment of patients with uncontrolled asthma (whose lives remain

impacted by asthma despite current treatment with LABA/ICS), and the

regulatory submission of this investigational once-daily inhaled

combination treatment has recently been accepted for review by the

European Medicines Agency (EMA). This formulation combines the

comprehensive bronchodilation, rendered by indacaterol acetate (a LABA

[long-acting beta agonist]) and glycopyrronium bromide (a LAMA

[long-acting muscarinic receptor antagonist]), with the

anti-inflammatory action of mometasone furoate (high- or medium-dose ICS

[inhaled corticosteroid]) in a precise once-daily formulation, delivered

via the dose-confirming Breezhaler(R) device. Glycopyrronium bromide and

certain use and formulation intellectual property were exclusively

licensed to Novartis in April 2005 by Sosei Heptares and Vectura.

Mometasone furoate is exclusively licensed to Novartis from a subsidiary

of Merck & Co., Inc., Kenilworth, NJ, USA, for use in QVM149 (Worldwide

excluding US).

About the PALLADIUM Study[2]

PALLADIUM is a multicenter, randomized, 52-week treatment, double-blind,

triple-dummy, parallel-group study, to assess the efficacy and safety of

the indacaterol acetate and mometasone furoate (IND/MF) combination

compared with mometasone furoate (MF) alone in patients with asthma.

The purpose of the trial is to evaluate the efficacy and safety of two

different doses of IND/MF (150/160 ug and 150/320 ug delivered via

Breezhaler(R) ) compared with two respective MF doses (400 ug and 800

ug) delivered via Twisthaler(R) (total daily dose) in patients with

uncontrolled asthma.

All patients were required to be on a stable dose of medium or high dose

inhaled corticosteroids (ICS), or low dose long-acting beta agonist

(LABA)/ICS for at least 1 month prior to entering into the run-in

period.

2216 male and female patients (including 107 adolescents, aged >=12 to

<18 years old) were randomized to receive either IND/MF 150/160 ug

delivered via Breezhaler(R) (n=439); IND/MF 150/320 ug delivered via

Breezhaler(R) (n=445); MF 400 ug delivered via Twisthaler(R) (n=444); MF

800 ug delivered via Twisthaler(R) (n=442); or salmeterol

xinafoate/fluticasone propionate 50/500 ug delivered via Accuhaler(R)

(n=446).

The primary endpoint was to demonstrate the superiority of QMF149

delivered via Breezhaler(R) to MF delivered via Twisthaler(R) in terms

of trough FEV(1) after 26 weeks of treatment in patients with asthma.

The key secondary objective was to demonstrate the superiority of IND/MF

(150/160 and 150/320 ug combined) to MF doses (400 and 800 ug combined)

in terms of ACQ-7 score after 26 weeks of treatment in patients with

asthma.

About the PLATINUM Clinical Development Program

The PLATINUM program is the Novartis Phase III clinical development

program supporting the development of QVM149 and QMF149. It includes

four studies: the QUARTZ study, which compares a low dose of indacaterol

acetate and mometasone furoate (IND/MF) with mometasone furoate (MF)

alone; the PALLADIUM study, which compares IND/MF with MF and

salmeterol/fluticasone; the IRIDIUM study which compares indacaterol

acetate, glycopyrronium bromide and mometasone furoate (IND/GLY/MF) with

IND/MF and salmeterol/fluticasone; and the ARGON study, which compares

IND/GLY/MF with a combination of salmeterol/fluticasone and tiotropium.

About Uncontrolled Asthma

Patients with asthma who have poor symptom control or frequent

exacerbations despite current therapy may be considered uncontrolled.

International guidelines such as the ERS/ATS criteria developed by The

European Respiratory Society/American Thoracic Society Task Force and

Global Initiative for Asthma (GINA) provide exact definitions depending

on the frequency of symptoms, reliever use, activity limitation and

exacerbations[3],[4].

Despite current therapy, over 40% of patients with asthma at GINA Step

3, and over 45% at GINA Steps 4 and 5 remain uncontrolled[3],[5].

Patients with uncontrolled asthma may downplay or underestimate the

severity of their disease, and are at a higher risk of exacerbation,

hospitalization or death[6],[7],[8]. Unresolved barriers such as

treatment mismatch, safety issues with oral corticosteroid, and

ineligibility for biologics have created an unmet medical need in

asthma[9],[10].

About Novartis in Respiratory

Over the last 60 years, there have been two breakthroughs in asthma care,

inhalers in the 1960s and more recently biologics. They have helped

patients with asthma cope with their condition, but a majority are still

suffering from exacerbations and symptoms, severely affecting their

quality of life. The Novartis ambition is to reimagine asthma care.

Novartis is a leading respiratory company that drives novel advances to

improve the lives of those living with lung conditions around the world.

Through courageous innovation and close partnership with patients and

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September 30, 2019 01:20 ET (05:20 GMT)