CONNECT1 Study Published in Journal of Allergy and Clinical Immunology: In Practice Evaluates the Potential of ProAir® Digihaler® (albuterol sulfate) Inhalation Powder and Digihaler System to Help Improve Asthma Management

Results from the study showed adults and children aged 13 and older with uncontrolled asthma using the ProAir Digihaler and its integrated system had 85.3% higher odds of improving their asthma control after three months compared with those using standard of care albuterol inhalers

Physicians reported more interactions with patients on poor inhaler technique based on objective data from the Digihaler System versus standard of care

CONNECT1 is the first clinical study to evaluate ProAir Digihaler and its integrated system compared to standard of care, and the first to evaluate the Digihaler system in asthma control

TEL AVIV, Israel & PARSIPPANY, N.J.--(BUSINESS WIRE)--Teva Pharmaceuticals, a U.S. affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA), today announced that full results from the CONNECT1 study evaluating the ProAir^® Digihaler^® (albuterol sulfate) Inhalation Powder and the Digihaler System in the management of asthma patients compared to standard of care (SoC) albuterol reliever therapy, were published online ahead of print in The Journal of Allergy and Clinical Immunology: In Practice. The study found patients who used the ProAir Digihaler had reductions in weekly average daily short-acting beta agonist (SABA) inhalations and an increase in weekly number of SABA-free days. In addition, patients in the ProAir Digihaler group had a higher number of discussions with physicians around adherence and inhaler technique prompted by the objective data provided by ProAir Digihaler versus patients who used SoC albuterol inhalers.

“Asthma remains one of the most common and challenging chronic health conditions in adults and children, many of whom have poorly-controlled disease leading to increased symptoms, exacerbations and healthcare resource utilization. Asthma management is complicated, and overuse and misuse of rescue medications is a common problem that contributes to poor asthma control,” said Flavia C.L. Hoyte, M.D., Associate Professor of Allergy and Immunology at National Jewish Health in Denver, Colorado, and University of Colorado Hospital, Aurora, Colorado. “This study highlights the potential of a digital health tool to support asthma management and physician-patient interactions and discussions around inhaler technique and adherence, as recommended by asthma guidelines.”

CONNECT1 was a 12-week, multicenter, open-label, randomized, parallel group feasibility study to evaluate the role of the ProAir Digihaler and the Digihaler System in 333 adults and children (aged ≥13) with uncontrolled asthma, defined by Asthma Control Test (ACT) score of <19. Patients were randomized 1:1 to the ProAir Digihaler or SoC albuterol inhaler. In the ProAir Digihaler group, patients’ inhalation data, including inhalation quantity and quality, were monitored once or more per week via a physician-facing dashboard. The study’s primary endpoint was clinically meaningful improvement in ACT score, defined as achieving a total ACT score ≥20 or an increase of at least three units from baseline at 12 weeks. A Bayesian statistical analysis, adjusted for baseline ACT score and random site effect, was used to understand the effectiveness of the ProAir Digihaler and system with respect to this primary outcome. Participants in the Digihaler System group were trained on the use of the Digital System, including instructions on how to use both the inhaler and smart device app.

Study Results¹

Patients using the ProAir Digital System (n=167) had a higher probability (85.3%) for clinically meaningful improvements in asthma control versus those using SoC (non-digital) albuterol inhalers (n=166) after three months of treatment. In addition, well-controlled asthma (ACT score of ≥20) or an improvement in asthma control (increase in ACT score by ≥3 units) was achieved at Week 12 by 92/150 (61%) of participants in the Digihaler group, compared with 89/163 (55%) in the SoC group.²

More physician-reported interactions due to poor inhaler technique were seen in the Digihaler group compared with the SoC group (52 vs 1, respectively). The Digihaler group also had fewer overall interactions (i.e., office visits or telephone calls) that had been planned during a prior visit versus the SoC group (54 vs 104, respectively). Overall, 85 interactions in the patients using the Digihaler System were reported because of data observed due to information observed from the Digihaler System dashboard; of these, 32 (37.6%) interactions were due to increased SABA use. Participants using the Digihaler System had more discussions with their HCP on inhaler technique and/or adherence than those receiving SoC (107 vs 44 discussions, respectively).

An increase in weekly number of SABA-free days was observed over 12 weeks, from 3.4 at Week 1 to 4.6 at Week 12, among patients using the ProAir Digihaler. A decrease in weekly average daily SABA inhalations, from 9.1 at Week 1 to 6.3 at Week 12, was also observed among those in the Digihaler System group.

The number of participants that experienced ≥1 adverse events (AE) was similar across the two groups (28 in the ProAir Digihaler group versus 26 in the SoC group). No AEs led to discontinuation or were considered device-related.

The study had several limitations which could have impacted results, including differences between sites regarding app synchronization and dashboard monitoring, a lack of thresholds for HCP action, the study’s short duration of three months, and the fact that the study was conducted during the COVID pandemic.

“Digital health tools are an increasingly important option for helping address unmet needs in asthma care,” said Manny Montalvo, Senior Vice President, Head of Digital Health & Innovation at Teva. “As shown in this study, a ‘smart’ digital health product like the ProAir Digihaler System that provides sensor-connected, fully integrated digital technology and objective data on inhaler use can elicit more discussions between physicians and patients on inhaler use and technique that can lead to greater adherence to treatment and reduced risk of asthma exacerbations.”

Initial findings from CONNECT1 were presented recently at the European Respiratory Society (ERS) International Congress 2022, held September 4-6 in Barcelona, Spain. The study’s full results will be presented at the American College of Allergy, Asthma & Immunology (ACAAI) 2022 Annual Scientific Meeting, November 10-14 in Louisville, Kentucky.

About ProAir Digihaler

The Digihaler Inhalers are the first family of smart inhalers that capture personal inhaler data and help inform patients’ asthma treatment plan. ProAir Digihaler (albuterol sulfate) Inhalation Powder is the first and only breath-actuated, digital short-acting beta agonist (SABA) inhaler with built-in flow sensors that detect, record and store objective data showing how often and how well patients use their rescue inhaler, as measured by inspiratory flow. Patients are able to view their data on the Digihaler app, including inhaler use patterns over time, and can share it with a healthcare provider to facilitate dialogue and personalize treatment discussions.

ProAir Digihaler Indications and Usage

ProAir Digihaler (albuterol sulfate) Inhalation Powder is a prescription medicine used in people ≥4 years of age for the treatment or prevention of bronchospasm in people who have reversible obstructive airway disease and for the prevention of exercise-induced bronchospasm.

Important Safety Information About ProAir Digihaler

• Contraindications: ProAir Digihaler (albuterol sulfate) Inhalation Powder is contraindicated in patients with hypersensitivity to albuterol or patients with a severe hypersensitivity to milk proteins. Rare cases of hypersensitivity reactions, including urticaria, angioedema, and rash have been reported after the use of albuterol sulfate. There have been reports of anaphylactic reactions in patients using inhalation therapies containing lactose
• Paradoxical Bronchospasm: ProAir Digihaler can produce paradoxical bronchospasm that may be life-threatening. Discontinue ProAir Digihaler and institute alternative therapy if paradoxical bronchospasm occurs
• Deterioration of Asthma: Need for more doses of ProAir Digihaler than usual may be a marker of acute or chronic deterioration of asthma and requires reevaluation of treatment, such as possible need for anti-inflammatory treatment, e.g., corticosteroids
• Use of Anti-Inflammatory Agents: ProAir Digihaler alone may not be adequate to control asthma in many patients. Early consideration should be given to adding anti-inflammatory agents, e.g., corticosteroids
• Cardiovascular Effects: ProAir Digihaler, like other beta-adrenergic agonists, can produce clinically significant cardiovascular effects in some patients, as measured by heart rate, blood pressure, and/or symptoms. If such effects occur, the drug may need to be discontinued. ProAir Digihaler, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension
• Do Not Exceed Recommended Dose: Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma
• Hypersensitivity Reactions including Anaphylaxis: Immediate hypersensitivity reactions may occur after administration of albuterol sulfate, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema. Hypersensitivity reactions including anaphylaxis, angioedema, pruritus, and rash have been reported with the use of therapies containing lactose, an inactive ingredient in ProAir Digihaler
• Coexisting Conditions: ProAir Digihaler, like all sympathomimetic amines, should be used with caution in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus; and in patients who are unusually responsive to sympathomimetic amines
• Hypokalemia: As with other beta-agonists, ProAir Digihaler may produce significant hypokalemia in some patients. The decrease is usually transient, not requiring supplementation
• Most common adverse reactions (≥1% and >placebo) are back pain, pain, gastroenteritis viral, sinus headache, urinary tract infection, nasopharyngitis, oropharyngeal pain and vomiting
• Drug Interactions: Other short-acting sympathomimetic bronchodilators should not be used concomitantly with ProAir Digihaler
  • Beta-Blockers: Beta-adrenergic-receptor blocking agents not only block the pulmonary effect of beta-agonists, such as ProAir Digihaler, but may produce severe bronchospasm in asthmatic patients. Therefore, patients with asthma should not normally be treated with beta-blockers
  • Diuretics: Caution is advised in the coadministration of beta-agonists with non-potassium sparing diuretics (such as loop or thiazide diuretics). Consider monitoring potassium levels
  • Digoxin: Carefully evaluate the serum digoxin levels in patients who are currently receiving digoxin and ProAir Digihaler
  • Monoamine Oxidase Inhibitors or Tricyclic Antidepressants: ProAir Digihaler should be administered with extreme caution to patients being treated with these agents, or within 2 weeks of discontinuation of these agents, because the action of albuterol on the cardiovascular system may be potentiated. Consider alternative therapy

Please read the full Prescribing Information.

About Teva

Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) has been developing and producing medicines to improve people’s lives for more than a century. We are a global leader in generic and specialty medicines with a portfolio consisting of over 3,500 products in nearly every therapeutic area. Around 200 million people around the world take a Teva medicine every day, and are served by one of the largest and most complex supply chains in the pharmaceutical industry. Along with our established presence in generics, we have significant innovative research and operations supporting our growing portfolio of specialty and biopharmaceutical products. Learn more at www.tevapharm.com.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, which are based on management’s current beliefs and expectations and are subject to substantial risks and uncertainties, both known and unknown, that could cause our future results, performance or achievements to differ significantly from that expressed or implied by such forward-looking statements. You can identify these forward-looking statements by the use of words such as “should,” “expect,” “anticipate,” “estimate,” “target,” “may,” “project,” “guidance,” “intend,” “plan,” “believe” and other words and terms of similar meaning and expression in connection with any discussion of future operating or financial performance. Important factors that could cause or contribute to such differences include risks relating to the development and commercial success of our digihaler products family, including ProAir Digihaler; our ability to successfully compete in the marketplace, including our ability to develop and commercialize biopharmaceutical products, competition for our specialty products, including AUSTEDO®, AJOVY® and COPAXONE®; our ability to achieve expected results from investments in our product pipeline, our ability to develop and commercialize additional pharmaceutical products, and the effectiveness of our patents and other measures to protect our intellectual property rights; our substantial indebtedness; our business and operations in general, including uncertainty regarding the COVID-19 pandemic and the governmental and societal responses thereto; our ability to successfully execute and maintain the activities and efforts related to the measures we have taken or may take in response to the COVID-19 pandemic and associated costs therewith; costs and delays resulting from the extensive pharmaceutical regulation to which we are subject or delays in governmental processing time due to travel and work restrictions caused by the COVID-19 pandemic; compliance, regulatory and litigation matters, including failure to comply with complex legal and regulatory environments; other financial and economic risks; and other factors discussed in our Quarterly Report on Form 10-Q for the second quarter of 2022 and in our Annual Report on Form 10-K for the year ended December 31, 2021, including in the section captioned “Risk Factors.” Forward-looking statements speak only as of the date on which they are made, and we assume no obligation to update or revise any forward-looking statements or other information contained herein, whether as a result of new information, future events or otherwise. You are cautioned not to put undue reliance on these forward-looking statements.

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¹ Hoyte FCL, Mosnaim GS, Rogers L, Safioti G, Brown R, Li T, DePietro M, Reich M, Hill TD, Wechsler ME, Effectiveness of a digital inhaler system for patients with asthma: a 12-week, open-label, randomized study (CONNECT1), The Journal of Allergy and Clinical Immunology: In Practice (2022), doi: https://doi.org/10.1016/j.jaip.2022.08.023.
² Modified Intention-to-treat (mITT) population

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