Employee Of Novartis Research Articles

P248 Subcutaneous secukinumab 150 mg provides rapid and sustained relief in total and nocturnal back pain, morning stiffness and fatigue in patients with active AS over 4 years

Abstract Background Ankylosing spondylitis (AS) is a chronic inflammatory condition with pain, stiffness and fatigue reported as the most troubling symptoms. Early and sustained relief of these symptoms is essential for effective management. Secukinumab provided sustained relief from pain and fatigue in AS patients over 2 years in the MEASURE 2 study. We report the effect of subcutaneous secukinumab 150 mg on key clinical symptoms (pain, morning stiffness and fatigue) in AS patients over 208 weeks in MEASURE 2. Methods This post-hoc analysis of MEASURE 2 assessed mean change from baseline to Week 208 in total and nocturnal back pain scores (by VAS [0-100]; ASAS outcome component), overall level of spinal pain (neck, back or hip) from BASDAI scores, and morning stiffness (overall level; mean of question 5 and 6 of BASDAI score). Additionally, the SF-36 physical component summary score, overall level of fatigue (BASDAI question 1), FACIT-Fatigue score and patients meeting minimal clinically important difference (MCID) criteria across multiple clinical domains were assessed. Data are shown for patients originally randomised to secukinumab 150 mg and placebo. Data are reported as observed for the overall population and by prior TNF inhibitor (TNFi) therapy status (naive vs inadequate response [IR]). Results Baseline characteristics were comparable across secukinumab 150 mg (N = 72) and placebo (N = 74) groups; total mean back pain score was 67.7±17.79, nocturnal back pain score was 64.9±19.58 and morning stiffness was 6.5±2.11. Secukinumab 150 mg-treated patients reported rapid and early reductions in pain scores by Week 4, which were sustained through Week 208 (Table 1). Improvements with secukinumab 150 mg were reported for all key clinical symptoms by Week 4, which were sustained at Week 208. A higher proportion of secukinumab 150 mg-treated patients met MCID criteria at Week 16 vs placebo across multiple clinical domains, which was sustained or further improved through Week 208. Improvements were observed in TNFi-naive and -IR patients, with a greater magnitude of improvement in TNFi-naive patients. Conclusion Secukinumab 150 mg was associated with rapid and clinically meaningful improvements in total and nocturnal back pain, morning stiffness and fatigue, with improvements sustained over 4 years of treatment. Disclosures H. Marzo-Ortega: Consultancies; AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB. Member of speakers’ bureau; AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB. Grants/research support; Janssen, Novartis. C. Miceli-Richard: Consultancies; Pfizer, Roche, UCB, Wyeth, Merck. Member of speakers’ bureau; Abbott, Bristol-Myers Squibb, Merck, Pfizer, Roche, Schering-Plough, Wyeth. Grants/research support; AbbVie, Bristol-Myers Squibb, Novartis, Merck, Pfizer, Wyeth. S. Gill: Consultancies; AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Amgen, Sanofi-Genzyme. Other; AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Amgen, Sanofi-Genzyme. M. Magery: Consultancies; Eli Lilly, Novartis. Grants/research support; AbbVie, UCB, Amgen. P.G.P. Machado: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. A. Shete: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. J. Wang: Other; Employee of Novartis. S. Rohrer: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. A. Deodhar: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, GSK, Galapagos, Janssen, Novartis, Pfizer, UCB. Grants/research support; Eli Lilly, GSK, Novartis, Pfizer, Boehringer Ingelheim, Bristol-Myers Squibb, UCB.

P254 Secukinumab provides rapid and sustained improvement in joint tenderness and swelling in patients with PsA: 2-year results from the Phase 3 FUTURE 5 study

Abstract Background Tender joint count (TJC) and swollen joint count (SJC) are components of composite measures used to assess treatment response, which may be impacted by confounding factors. TJC and SJC used in psoriatic arthritis (PsA), which can affect small joints of the feet, assess 78 and 76 joints. TJC and SJC are effective measures of synovitis, a key measure of disease activity. We report 16-week through 2-year effects of secukinumab upon 78 TJC and 76 SJC in PsA patients in FUTURE 5. Methods 996 patients with active PsA were randomised to subcutaneous secukinumab 300 mg with loading dose (LD), 150 mg with LD, 150 mg without LD or placebo. All patients received secukinumab or placebo at baseline, Weeks 1, 2, 3 and 4, and every 4 weeks thereafter. Placebo-treated patients were re-randomised to secukinumab 300 or 150 mg at Week 16 (non-responders) or 24 (responders). Secukinumab dose was escalated from 150 to 300 mg starting at Week 60 and maintained thereafter, if active signs of disease were observed by the physician. 78 TJC and 76 SJC were assessed at baseline, Weeks 1, 2, 3 and 4, every 4 weeks until Week 52, every 8 weeks until Week 92 and at Week 104. ACR20 response, 78 TJC and 76 SJC results are reported for the overall population over 2 years of treatment. Data are reported as observed. Results Baseline characteristics were comparable across treatment arms (Table 1). 783/996 (78.6%) patients completed 104 weeks of treatment. All secukinumab dose regimens (300 mg with LD, 150 mg with LD and 150 mg without LD) demonstrated rapid-onset ACR20 responses that were superior to placebo at Week 16 (adjusted P values: P < 0.0001 for all secukinumab regimens) and increased to 77.0%, 79.4% and 82.4% at Week 104, respectively. Adjusted 78 TJC and adjusted 76 SJC improved in all secukinumab groups vs placebo by Week 4 through Week 16 and were sustained after 2 years of treatment (Table). Numerical differences were comparable between secukinumab doses. Conclusion Secukinumab provided rapid and sustained improvements in 78 TJC and 76 SJC over 2 years of treatment in patients with active PsA. Disclosures I. McInnes: Consultancies; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB. Honoraria; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB. H. Chinoy: Honoraria; Novartis. D. Asquith: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. A. White: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. C. Gaillez: Shareholder/stock ownership; Novartis, Bristol-Myers Squibb. Other; Employee of Novartis.

P253 Secukinumab provides sustained improvements in tender and swollen joint counts: 5year results from the Phase 3 FUTURE 2 study

Abstract Background Secukinumab, a fully human monoclonal antibody that neutralises interleukin-17A, demonstrated long-term efficacy and tolerability in psoriatic arthritis (PsA) patients in FUTURE 2. Tender joint count (TJC) and swollen joint count (SJC) scores are components of composite measures used to assess treatment response, which can include confounding factors. TJC and SJC were developed for rheumatoid arthritis, assessing 68 and 66 joints, respectively. Later, these scores evolved for use in PsA, which can affect small joints of the feet, assessing 78 and 76 joints. TJC and SJC measure synovitis, a key assessment of disease activity. Herein, we report the 5-year efficacy of secukinumab on reduction of 78 TJC and 76 SJC in FUTURE 2. Methods 397 patients with active PsA were randomised to subcutaneous secukinumab loading dose (300, 150, 75 mg) or placebo at baseline, Weeks 1, 2, 3 and 4, and every 4 weeks thereafter. Placebo-treated patients were re-randomised to secukinumab 300 or 150 mg at Week 16 (non-responders) or 24 (responders). Secukinumab dose was escalated from 150 to 300 mg, and 75 to 150 or 300 mg starting at Week 128 and maintained thereafter, if active signs of disease were observed based on physician’s assessment. Data are reported as observed for secukinumab 300 and 150 mg (approved PsA doses) over 5 years (2 years of core study and 3-year extension). Results Baseline characteristics were comparable across treatment arms (Table 1). Overall, 62.5% (248/397) of all patients randomised completed 260 weeks of treatment. Of these, 48/65 (73.8%) and 49/66 (74.2%) patients randomised to secukinumab 300 and 150 mg achieved ACR20 at Week 260, respectively. Improvements in adjusted 78 TJC and 76 SJC change from baseline were sustained from Week 16 to Week 260 in all treatment groups (Table 1). At Week 260, mean change from baseline in adjusted 78 TJC/76 SJC was −12.8/−9.3 and −15.1/−8.5 for the secukinumab 300 mg and 150 mg group (including patients up-titrated to 300 mg), respectively. Numerical differences were comparable between secukinumab doses. Conclusion Secukinumab 300 and 150 mg provided sustained improvements in 78 TJC and 76 SJC scores over 5 years; numerical differences were comparable between secukinumab doses. Disclosures I. McInnes: Consultancies; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB. Honoraria; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB. H. Chinoy: Honoraria; Novartis. D. Asquith: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. A. White: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. C. Gaillez: Shareholder/stock ownership; Novartis, Bristol-Myers Squibb. Other; Employee of Novartis.

Chemotherapy De-Escalation Using an <sup>18</sup>F-FDG PET/CT–Based, Pathologic Response–Adapted Strategy in HER2-Positive Early Breast Cancer: The PHERGain Trial

Chemotherapy De-Escalation Using an <sup>18</sup>F-FDG PET/CT–Based, Pathologic Response–Adapted Strategy in HER2-Positive Early Breast Cancer: The PHERGain Trial

A Comprehensive Review of Methods to Measure Oral Oncolytic Dose Intensity Using Retrospective Data.

Understanding the real-world use of oral oncolytics is essential to assess drug effectiveness. Retrospective analyses using medical and pharmacy claims data allow observation of drug use patterns and health outcomes. However, studies of medication adherence to oral oncolytics may not be sufficient in characterizing exposure because they typically measure refill frequency, not the administered dose or dose changes. Patients who appear fully adherent by traditional measures may be receiving different doses and experiencing differing effectiveness. Relative dose intensity (RDI) is a measure that has been used for intravenous drugs to capture the amount of a particular chemotherapeutic agent administered per unit of time (dose intensity), expressed as the fraction of the amount recommended in evidence-based guidelines. Such a measure would be useful for real-world studies of comparative effectiveness to characterize patient exposure to oral oncolytics. To identify studies that used administrative claims data to measure real-world oral oncolytic dose intensity, RDI, or similar constructs. Two health sciences librarians conducted a literature search (PubMed, January 1, 1809-February 6, 2018) including terms in each of the following concept areas: oncology drugs, dosage, and retrospective data sources. At least 2 reviewers scanned each title and abstract of publications retrieved from PubMed. Abstracts that indicated the study reported dose or related concepts and oral oncolytics using retrospective data sources were marked for full-text review. During full-text review, papers were excluded if they did not study oral oncolytics (i.e., only described intravenous chemotherapy); if they did not report drug dosage; or if the study was not retrospective. Resulting studies were included for full-text data extraction. Of the 1,640 publications returned from the search, 41 were marked for full-text review. Full-text review established that 17 studies addressed a concept related to dose of oral oncolytics using retrospective data. Twenty-four studies were excluded: 11 did not measure dose; 9 did not study oral oncolytics; and 4 were not retrospective studies. Among the 17 articles marked for extraction, 5 articles reported dose intensity or RDI using medical records or electronic health record (EHR) data. This study reveals not only the need for a claims-based measure of dose intensity for oral oncolytics, but also provides a basis for the development of such a measure based on previous EHR-based studies. While several claims data studies have characterized oral oncolytic dosing and duration, we found that no studies combined these dimensions into a single measure such as dose intensity. Methods using EHR data may be translatable to a claims data study. Future research is needed to develop and validate such measures. Novartis Pharmaceuticals provided funding for this study and is a manufacturer of oral onalytics, which is under study in this article. Arcona and Zacker are employees of Novartis. Slejko reports grants from PhRMA, PhRMA Foundation, and Takeda Pharmaceuticals and consulting fees from Pfizer, outside the submitted work. Stuart reports consulting fees from the University of Maryland during the study. The other authors have nothing to disclose. The preliminary findings of this study were presented in a poster at AMCP Nexus 2018, October 22-25, 2018, in Orlando, FL.

Drug Treatment Value in a Changing Oncology Landscape: A Literature and Provider Perspective.

The U.S. health care system's transition to a value-based reimbursement model holds important implications for medical innovation, care delivery, and value-based assessments of therapeutic interventions. This transition has been especially noteworthy in oncology, with substantial ongoing changes to payer reimbursement and the provider landscape, as well as the introduction of value frameworks to guide drug treatment decision making. The implications of these changes for provider assessments of drug value and evidence needs remain unclear. To understand provider perspectives on drug value assessment and the utility of existing oncology value frameworks by identifying (a) key value-based trends in the evolving oncology landscape, (b) provider definitions of drug value, (c) the role of existing value frameworks in provider decision making, and (d) future provider evidence needs for making value-based treatment decisions. We conducted a literature review to identify existing oncology value frameworks and definitions of drug treatment value in oncology. Using a structured discussion guide informed by this literature review, we conducted 12 telephone-based in-depth interviews in November and December 2017 with U.S. oncology providers involved in organizational drug treatment and formulary decision making within their practices. Responses to interview questions were analyzed and reported as averages and percentages across participants. Of 293 publications identified by keyword searches, 35 relevant articles were identified. Among these, the literature review identified no common definition for providers to assess drug value. Interview research participants described large ongoing changes in the oncology provider landscape, with economic pressures from payers as the foremost leading factor. Although 5 value frameworks were found in the literature, interviews found that in practice few providers consider these value frameworks to be key influences when evaluating treatment or formulary decisions. Furthermore, while 83% of participants' organizations employed some form of internal clinical pathways, only the minority (25%) with pathways integrated in their electronic medical record (EMR) systems saw these pathways as significantly affecting clinicians' drug treatment decision making. To aid the ongoing shift from volume-based to value-based care, we found that, rather than value frameworks, providers are looking for patient-level tools to make more appropriate drug decisions. Payer reimbursement pressures are leading to radical changes in the oncology provider landscape, and there is a need for improved guidance for providers in assessing drug value. In particular, this study identifies the need for a timely and multifaceted summary of information required to assess the value of alternative treatment options for a given patient. Manufacturers also need to make significant strides to help generate and improve the dissemination of evidence to support the value of their therapies. Funding for this work was provided by Novartis Pharmaceuticals. The study sponsor was involved in study design, data interpretation, and data review. All authors contributed to the development of the manuscript and maintained control over the final content. Sasane, Howe, Wong, and Zacker were employees of Novartis at the time of this study. Frois, Jarvis, and Grice are or have been employed by Analysis Group, which received a grant from Novartis for this research. At the time of this study, Analysis Group received funding from multiple manufacturers with oncology products in their portfolio during this time period, including, but not limited to, Astellas and Genentech.

Modeling Episode-Based Payments for Cancer Using Commercial Claims Data.

Innovative health care reimbursement models are gaining attention as a way to move away from a payment system that rewards quantity of service over quality of care. One such alternative payment model is episode-based payment, such as the Oncology Care Model (OCM) being piloted by the Center for Medicare & Medicaid Innovation. To adapt the OCM methodology to a commercially insured population to understand the challenges and potential implications of implementing an episode-based payment model in a commercial health plan. Administrative claims databases from 3 regional commercial health plans were used to identify continually eligible patients (aged ≥ 18 years) with breast cancer, lung cancer, melanoma, or chronic myelogenous leukemia (CML). Episode triggers were identified using the OCM methodology. In calculating the episode-based payments, adjustments to the OCM methodology were necessary to adapt the methodology to a commercial population, since not all Medicare data elements used in the OCM algorithm are available in commercial claims data. The adapted OCM-like model was applied to data from 39,967 patients with 1 of 4 cancer types. Approximately 13% of patients had at least 1 episode per year and the average number of episodes per patient per year for patients with at least 1 episode ranged from 1.42 for patients with melanoma to 1.94 for patients with CML. The percentage of total annual costs included in episodes was 49%, 60%, 34%, and 52% for breast cancer, lung cancer, melanoma, and CML, respectively. As health care financing shifts to alternative payment models, insurers may look to adopt episode-based payments for oncology, similar to the OCM. This study shows that implementing an OCM-like model in a commercial health plan is feasible but will require adjustments to the OCM algorithm to make it implementable and applicable to populations beyond Medicare. This study was conducted by Magellan Rx Management with funding contributed by Novartis. Zacker is an employee of Novartis. The other authors are employed by Magellan Rx Management and have nothing to disclose.

Health Care Utilization and Cost Associated with Biologic Treatment Patterns Among Patients with Moderate to Severe Psoriasis: Analyses from a Large U.S. Claims Database.

Discontinuation or switching of biologic treatment among patients with psoriasis imposes a great economic burden. To assess the health care utilization and costs associated with nonswitchers, switchers, and discontinuers of biologics among patients with moderate to severe psoriasis. Patients aged ≥ 18 years with ≥ 1 pharmacy claim for a biologic (adalimumab, etanercept, infliximab, and ustekinumab) between January 1, 2012, and June 30, 2015 (identification period), were identified in the Truven Health Analytics MarketScan Commercial and Medicare Supplemental databases. At the time of biologic initiation (index date), eligible patients were continuously enrolled with medical and pharmacy claims for ≥ 1 year before (baseline period) and ≥ 1 year after the index date (follow-up period). Patients had ≥ 1 psoriasis diagnosis and had no pharmacy claims for the index biologic during the baseline period. Patients were categorized into 3 mutually exclusive groups based on their biologic treatment pattern during the 1-year follow-up period: nonswitchers (patients who remained on their index biologic), switchers (patients who had a prescription for a biologic therapy other than their index biologic), and discontinuers (patients who had gaps in prescription claims [> 90 days for adalimumab, infliximab, and etanercept; > 120 days for ustekinumab]). Descriptive analyses were used to summarize baseline patient demographics, clinical characteristics, resource utilization, and health care costs (inflated to 2016 costs) across the 3 groups. Adjusted health care resource utilization and costs during the 1-year follow-up were estimated, controlling for age, sex, geographic region, insurance plan type, index drug, index year, Charlson Comorbidity Index score, resource utilization, total health care costs, and nonbiologic medications during the baseline period. Of the 8,710 patients with psoriasis included in the study, 5,000 (57.4%) were categorized as nonswitchers, 1,001 (11.5%) as switchers, and 2,709 (31.1%) as discontinuers. Emergency department and inpatient visits, respectively, were more common among switchers (adjusted incidence rate ratio [95% CI]: 1.10 [0.93-1.30] and 1.13 [0.84-1.53]) and discontinuers (1.50 [1.34-1.63] and 2.05 [1.70-2.48]) than among nonswitchers. Compared with nonswitchers, switchers had higher adjusted mean total health care costs (mean difference [95% CI]: $10,120 [$8,235-$12,033]), which were driven by increased prescription costs ($8,988 [$7,535-$10,610]) and medical costs ($2,746 [$1,090-$4,677]). Conversely, the adjusted mean total health care cost for discontinuers was lower than that for nonswitchers (mean difference [95% CI]: -$18,611 [-$20,254, -$17,025]) due to reduced prescription costs (-$20,486 [-$21,319, -$19,636]); however, discontinuers had a higher mean medical cost ($3,729 [$1,970-$5,527]). Switching or discontinuing biologics resulted in higher health care utilization and increased medical costs than remaining on the same biologic. These updated findings highlight the clinical and economic effects of discontinuing or switching biologic therapies in patients with psoriasis in clinical practice and may inform treatment and/or formulary decision making. This study was sponsored by Novartis Pharmaceuticals Corporation. Feldman has received consulting, speaking, and/or research support from Novartis, AbbVie, Celgene, Sun Pharma, Janssen, Lilly, and Ortho. Tian and Germino are employees of Novartis. Wang was an employee of KMK Consulting and worked as a consultant for Novartis at the time of this study. Portions of this work were presented at the 2017 Fall Clinical Dermatology Conference; October 12-15, 2017; Las Vegas, NV; the 2017 Las Vegas Dermatology Seminar; November 2-4, 2017; Las Vegas, NV; and the 2018 American Academy of Dermatology Annual Meeting; February 16-20, 2018; San Diego, CA.

71P - Phase I study of cemiplimab, a human monoclonal anti-PD-1, in patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC): Longer follow-up efficacy and safety data

Background: Cemiplimab (REGN2810) demonstrated a positive risk/benefit profile and produced antitumour activity in patients (pts) with advanced CSCC in the primary analysis, by independent central review, of a phase 1 CSCC expansion cohorts (ECs). We now report longer follow-up data from the CSCC ECs of the phase 1 study (NCT02383212). Methods: Pts with distantly metastatic or locally/regionally advanced CSCC who were not candidates for surgery were enrolled in ECs 7 and 8, respectively. All pts received cemiplimab 3 mg/kg by intravenous infusion over 30 minutes every 2 weeks for up to 48 weeks. Tumour measurements were performed every 8 weeks by RECIST 1.1 to determine overall response rate (ORR; complete response [CR] + partial response [PR]) according to intention to treat. The data cut-off date was Jan 20, 2018. Tumour response in this report was by investigator assessment. Results: A total of 26 pts were enrolled (21 M/5 F; 10 in EC 7, 16 in EC 8; median age: 72.5 years [range: 55–88]; ECOG performance status was 1 in 16 pts and 0 in 10 pts). Median duration of follow-up was 11.9 months (range: 1.1–18.2). Median duration of cemiplimab exposure was 36.0 weeks. The most common treatment-emergent adverse event (TEAE) of any grade was fatigue (26.9%). The only TEAEs of grade ≥3 that occurred in more than one pt were hypercalcaemia and skin infection (each 7.7%). ORR was 50.0% (95% CI: 29.9–70.1), with 2 CRs and 11 PRs; 5 patients had stable disease (SD), 6 had progressive disease, and 2 were not evaluable for response. Durable disease control rate (SD or response for ≥105 days) was 57.7% (95% CI: 36.9–76.6). The median time to response was 1.9 months (range: 1.7–7.5). The median duration of response has not been reached, and as of the data cut-off date, for pts with CR or PR, the observed duration of response exceeded 6 months in 9 pts and 12 months in 5 pts. Conclusions: The increasing duration of response in this analysis provides further evidence of a positive risk/benefit profile for cemiplimab in pts with advanced CSCC. Editorial acknowledgement: Medical writing support under the direction of the authors was provided by Emmanuel Ogunnowo, PhD, of Prime (Knutsford, UK) and funded by Regeneron Pharmaceuticals, Inc. and Sanofi according to Good Publication Practice guidelines. Clinical trial identification: NCT02383212. Legal entity responsible for the study: Regeneron Pharmaceutical, Inc. and Sanofi. Funding: Regeneron Pharmaceutical, Inc. and Sanofi. Disclosure: T.K. Owonikoko: Fees for consulting or advisory role: Novartis, Celgene, Lilly, Sandoz, Abbvie, Eisai, G1 Therapeutics, Takeda, Seattle Genetics, Bristol-Myers Squibb, MedImmune. A.K. Salama: Fees for consulting or advisory and speakers’ bureau roles: Bristol-Myers. E. Calvo: Research funding: Boehringer Ingelheim, Roche/Genentech, BMS, Novartis, PsiOxus, Nanobiotix, Janssen, Abbvie, PharmaMar, PUMA, Sanofi, Lilly, Pfizer, Merck, Nektar, Amcure, Amgen, AstraZeneca, Principia, Bayer, CytomX, H3, Incyte, Kura, Loxo, Macrogenics, Menarini, Merck, Serono, Merus, Millenium, Rigontec, Tahio, TesaroReceipt; Honoraria or consultation fees: Novartis, Nanobiotix, Janssen-Cilag, PsiOxus Therapeutics, Seattle Genetics, Pierre Fabre, Boehringer Ingelheim, Cerulean Pharma, EUSA, Abbvie, Celgene; Speaker’s bureau fees: Novartis. N.S. Yee: Institutional research funding: Boston Biomedical Inc., Merck and Co. Inc., Pharmacyclics, Regeneron Pharmaceuticals Inc; Travel/accommodation expenses: Daiichi Sankyo, Foundation Medicine, Caris Life Sciences. D. Mahadevan: Speakers’ bureau and travel, accommodation expenses: Abbvie. J. Niu: Consulting or advisory role fees: Genentech, Biodesix, Paradigm, Ignyta, AstraZeneca and Teueda. K. Kal Mohan: Employee and shareholder of Regeneron Pharmaceuticals, Inc. J. Li: Employee and shareholder of Regeneron Pharmaceuticals, Inc. and Novartis. E. Stankevich: Employee of Regeneron Pharmaceuticals, Inc., a shareholder of Regeneron Pharmaceuticals, Inc., Celgene, Bristol-Myers Squibb, and Merck. M. Mathias: Shareholder and an employee of Regeneron Pharmaceuticals, Inc. I. Lowy: Employee, shareholder, fees for travel and accommodation expenses, leadership: Regeneron Pharmaceuticals, Inc. M.G. Fury: Employee and shareholder of Regeneron Pharmaceuticals, INC.; patents, royalties, other intellectual property: Regeneron Pharmaceuticals, Inc. H.M. Babiker: Honoraria: Bayer, Sirtex; Consulting or advisory role fees: Celgene, Endocyte. All other authors have declared no conflicts of interest.

Effect of Fingolimod in Pediatric MS: Further Insights from Paradigms

BACKGROUND In PARADIGMS, a double-blind phase 3 trial in 215 pediatric MS patients (age 10 to <18 years), fingolimod administered for up to 2 years significantly reduced the annualized relapse rate (ARR) and the rate of new/newly enlarged T2 (n/neT2) lesions compared with interferon (IFN) β-1a. Here, we present further differences between the two treatment groups across various subpopulations, e.g. treatment-naive, younger/prepubertal patients, and results from a post-hoc analysis of disability progression. METHODS Predefined sensitivity/supportive analyses of the endpoints were performed after 1) excluding patients in the IFN β-1a arm who were positive for IFN neutralizing antibody (NAbs) at study end, and 2) evaluating patients who were treatment-naive. ARRs in patients at 10, 11, and 12 years were estimated based on predefined modeling extrapolations. Changes in expanded disability status scale (EDSS), and in 3-month (3M) and 6-month (6M) confirmed disability progression (CDP) were evaluated post-hoc. FINDINGS Excluding NAbs-positive patients (n=9) did not meaningfully change the primary and key secondary results (81·5% ARR reduction and 47·6% reduction in n/neT2 lesions, versus 81·9% and 52·6% in the overall population, respectively). The effect of fingolimod treatment in the treatment-naive subpopulation were 85·8% ARR reduction and 53·4% n/neT2 lesion reduction versus IFN β-1a (both p<0·001). ARR reductions in younger patients (≤12 years) estimated from the modeling extrapolation were 91·9%- 94·6% versus 83·8% for the overall population. The proportion of fingolimod-treated patients who had worsening in EDSS score at study end was half that of IFN β-1a-treated patients (10·5% versus 20·6%, p=0·043). There was a risk reduction in 3M-CDP of 77·2% (p=0·007) and 6M-CDP of 80·2% (p=0·040). INTERPRETATION Fingolimod in pediatric MS was associated with consistent control of disease activity across younger and treatment-naive patients. Fingolimod-treated patients versus IFN β-1a treated patients had less disability progression over treatment duration of up to 2 years. Funding: Novartis Pharma AG, Basel, Switzerland Declaration of Interest: KD received personal compensation for speaker activities from Novartis. PH received compensation for serving on a scientific advisory board from Novartis, and for speaking from Bayer Health care. BB has served as a remunerated central MRI reviewer for the present trial (Novartis). EW volunteers on an advisory board for a Novartis trial. She is a site PI for clinical trials with Roche and Novartis. JG in the last three years has received honoraria for lectures and consultancy fees from Bayer, Teva and Novartis. LK has received personal compensation for activities as a speaker, consultant and/or participant on an advisory board from Biogen Idec, Novartis, Teva Neurosciences and Multicell in addition, LK has royalty or license fees from ER Squibb & Sons, Avenir, Johnson & Johnson and Osmotica, and has received research support from Novartis, Biogen Idec, Celgene Corporation and Genentech. TC has received personal compensation for advisory boards/consulting for F. Hoffman-La Roche, Biogen and Novartis; TC has also received financial support for research activities from Biogen, Merck Serono, Verily and Novartis. TS, GLP and MM are employees of Novartis. Ethical Approval: The trial was conducted in accordance with the provisions of the International Conference on Harmonization Guidelines for Good Clinical Practice and the principles of The Declaration of Helsinki.12 The study protocol was approved by an institutional review board or ethics committee at each study site.

Treatment Patterns Among Patients with Psoriatic Arthritis Treated with a Biologic in the United States: Descriptive Analyses from an Administrative Claims Database.

In patients with psoriatic arthritis (PsA), limited data exist regarding patterns of biologic therapy use. To examine treatment patterns and therapy modifications in U.S. patients with PsA receiving a tumor necrosis factor inhibitor (TNFi) or an anti-interleukin (IL)-12/23 inhibitor. Adults with PsA who newly initiated a biologic therapy (index biologic) between January 1, 2013, and January 31, 2015, were included from the Optum Research Database. Biologic therapies comprised those that were approved by the FDA for the treatment of PsA at the time of the study initiation (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, or ustekinumab). Outcomes included adherence, persistence, and discontinuation of the index biologic; initiation of adjunctive medications (nonbiologics, including those commonly used for pain and/or inflammation); and dose escalation of the index biologic during the 12-month follow-up period. Of the 1,235 patients included, 52.5% were female, and mean (SD) age was 50.3 (12.1) years. The mean (SD) duration of persistence with a newly initiated index biologic (etanercept [48.1%], adalimumab [24.0%], infliximab [10.4%], golimumab [8.3%], ustekinumab [7.2%], or certolizumab pegol [2.0%]) was 246 (128) days; 44.5% of patients persisted with the index biologic for ≥ 12 months. During the 12-month follow-up period, 22.9% of patients switched to a different biologic, 26.8% discontinued without switching or restarting, and 5.8% discontinued and restarted the index biologic. Of the 1,010 patients who persisted with the index biologic for > 90 days, 45.6% received ≥ 1 adjunctive medication during the period from 90 days after the index date to the end of persistence or 12 months. The most commonly initiated adjunctive medications were corticosteroids (22.0%), opioids (17.1%), and nonsteroidal anti-inflammatory drugs (12.9%). Overall, 9.6% of patients had a dose escalation of the index biologic in the immediate 12-month post-index period. This real-world study of treatment patterns for PsA, which used a large U.S. claims database, demonstrated that the majority of patients with PsA discontinued their index biologic (TNFi or anti-IL-12/23 inhibitor) before 12 months. Nearly half of patients initiated an adjunctive medication, many of which were pain and conventional anti-inflammatory medications. This study was sponsored by Novartis Pharmaceuticals. Optum was commissioned by Novartis to conduct this study, but employment was not contingent on results of the study. Walsh is a paid consultant for Novartis. Adejoro was an employee of Optum at the time of the study and writing of the manuscript. Chastek is an employee of Optum. Palmer and Hur are employees of Novartis. Results of this study were presented as an abstract and poster at the Academy of Managed Care Pharmacy Nexus 2017; October 16-19, 2017; Dallas, TX; and the EULAR 2017 Annual European Congress of Rheumatology; June 14-17, 2017; Madrid, Spain.

Treatment Patterns Among Patients with Psoriatic Arthritis Treated with a Biologic in the United States: Descriptive Analyses from an Administrative Claims Database.

In patients with psoriatic arthritis (PsA), limited data exist regarding patterns of biologic therapy use. To examine treatment patterns and therapy modifications in U.S. patients with PsA receiving a tumor necrosis factor inhibitor (TNFi) or an anti-interleukin (IL)-12/23 inhibitor. Adults with PsA who newly initiated a biologic therapy (index biologic) between January 1, 2013, and January 31, 2015, were included from the Optum Research Database. Biologic therapies comprised those that were approved by the FDA for the treatment of PsA at the time of the study initiation (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, or ustekinumab). Outcomes included adherence, persistence, and discontinuation of the index biologic; initiation of adjunctive medications (nonbiologics, including those commonly used for pain and/or inflammation); and dose escalation of the index biologic during the 12-month follow-up period. Of the 1,235 patients included, 52.5% were female, and mean (SD) age was 50.3 (12.1) years. The mean (SD) duration of persistence with a newly initiated index biologic (etanercept [48.1%], adalimumab [24.0%], infliximab [10.4%], golimumab [8.3%], ustekinumab [7.2%], or certolizumab pegol [2.0%]) was 246 (128) days; 44.5% of patients persisted with the index biologic for ≥ 12 months. During the 12-month follow-up period, 22.9% of patients switched to a different biologic, 26.8% discontinued without switching or restarting, and 5.8% discontinued and restarted the index biologic. Of the 1,010 patients who persisted with the index biologic for > 90 days, 45.6% received ≥ 1 adjunctive medication during the period from 90 days after the index date to the end of persistence or 12 months. The most commonly initiated adjunctive medications were corticosteroids (22.0%), opioids (17.1%), and nonsteroidal anti-inflammatory drugs (12.9%). Overall, 9.6% of patients had a dose escalation of the index biologic in the immediate 12-month post-index period. This real-world study of treatment patterns for PsA, which used a large U.S. claims database, demonstrated that the majority of patients with PsA discontinued their index biologic (TNFi or anti-IL-12/23 inhibitor) before 12 months. Nearly half of patients initiated an adjunctive medication, many of which were pain and conventional anti-inflammatory medications. DISCLOSURES This study was sponsored by Novartis Pharmaceuticals. Optum was commissioned by Novartis to conduct this study, but employment was not contingent on results of the study. Walsh is a paid consultant for Novartis. Adejoro was an employee of Optum at the time of the study and writing of the manuscript. Chastek is an employee of Optum. Palmer and Hur are employees of Novartis. Study concept and design were contributed by Walsh, Chastek, Adejoro, Palmer, and Hur. Adejoro, Chastek, Walsh, Palmer, and Hur collected the data. Data interpretation was performed by Walsh, Palmer, Adejoro, Chastek, and Hur. The manuscript was written and revised by Walsh and Hur, along with the other authors. Results of this study were presented as an abstract and poster at the Academy of Managed Care Pharmacy Nexus 2017; October 16-19, 2017; Dallas, Texas; and the EULAR 2017 Annual European Congress of Rheumatology; June 14-17, 2017; Madrid, Spain.

Outcomes-Based Contracting Experience: Research Findings from U.S. and European Stakeholders.

Outcomes-based contracts (OBCs), a type of risk-sharing arrangement (RSA), have emerged as a promising avenue for payers to engage with pharmaceutical manufacturers to share risk and improve patient access to medicines via evaluation of real-world outcomes. To assess the level of recent OBC activity and stakeholder perceptions of these arrangements, as well as the outlook for future OBC activity from a payer and manufacturer perspective in the United States and EU-5 (France, Germany, Italy, Spain, and the United Kingdom). Using a structured questionnaire, interviews were conducted with 27 experts, including 14 U.S. payers, 5 EU-5 national payers, and 8 manufacturer pricing/market access executives (4 U.S., 4 EU-5). We also used the University of Washington's Performance Based Risk-Sharing (PBRS) database and other targeted publicly available information. Publicly disclosed information on OBCs understates the level of OBC activity, since many arrangements are confidential. Overall, U.S. and EU-5 interviewees generally expected that 2 to 3 times more OBCs would be implemented in the next 5 years than in the previous 5 years. Key drivers included the introduction of a national OBC framework in Spain, potentially a similar framework in the United Kingdom, a growing sickness fund activity in Germany, and a U.S. movement towards accountable care. Motivation for OBCs varied markedly across markets and stakeholders, with operational feasibility noted as a significant hurdle in the United States and France. Along with improving health outcomes, cost and financial risk reduction were the primary OBC motivators for payers, while potential access or reimbursement gains were key factors for manufacturers. Using direct input from U.S. and EU-5 payer and pharmaceutical manufacturer decision makers, this research suggests that high OBC growth is expected in the EU-5 and, to a more moderate extent, in the United States, particularly if clear, simpler OBC frameworks can be developed. This study was funded by Novartis Pharmaceuticals. Novartis employees were involved in all aspects of this study. Vegesna and Sasane are employed by and own stock in Novartis. Nazareth and Ko were employees of Novartis at the time of this study. Frois, Demean, Carpenter, and Wu are or have been employed by Analysis Group, which received a grant from Novartis for this research. Navarro received consulting fees from Novartis for his involvement in this research. Study concept and design were contributed by Sasane, Frois, Nazareth, and Wu. Navarro, Demean, and Frois took the lead in data collection, assisted by Carpenter, Ko, and Nazareth. Data interpretation was provided by Frois, Carpenter, Nazareth, and Ko, along with Sasane, Demean, Wu, and Navarro. The manuscript was written by Frois, Demean, Nazareth, and Ko, along with Sasane, Carpenter, Wu, and Navarro, and revised by Frois, Ko, and Vegesna, along with Sasane, Nazareth, Wu, and Navarro.

254P - Matching-adjusted indirect treatment comparison of ribociclib and palbociclib as first-line treatments for HR+, HER2– ABC

Background: Ribociclib (RIB) and palbociclib (PAL) combinations with letrozole (LET) vs LET alone have been evaluated in separate Phase 3 randomized controlled trials in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC); however, no head-to-head comparative studies have been conducted. Classic indirect treatment comparison (ITC) can lead to biased results due to differences in patient populations and trial designs. These differences can be corrected by using the matching-adjusted indirect comparisons (MAIC) technique. Here, we compare RIB and PAL in patients with HR+, HER2– ABC using MAIC. Methods: Individual patient data were available for the RIB trial (MONALEESA-2). As only published summary data were available for the PAL trial (PALOMA-2), RIB data were adjusted to closely match the PAL data. Data for RIB-treated patients were assigned weights so that weighted mean baseline characteristics matched those reported for PAL. Overall survival data have not been reported for PALOMA-2, thus only progression-free survival (PFS) data were compared. Adjusted hazard ratios (HRs) for PFS were calculated using weighted Cox regression models and used to calculate indirect HRs with 95% confidence intervals (CIs). Classic frequentist ITC was performed before and after adjustment. ITC of Grade 3/4 adverse events (AEs) was also performed. Results: The unadjusted PFS HR (95% CI) for RIB+LET vs LET was 0.556 (0.429; 0.721) and for PAL+LET vs LET was 0.580 (0.460; 0.720). MAIC adjustment for age, race, region, Eastern Cooperative Oncology Group status, disease stage at diagnoses, sites of metastases, and chemotherapy setting at baseline provided a RIB+LET vs LET HR estimate of 0.501 (0.365; 0.688). The HR for unadjusted ITC of RIB vs PAL was 0.959 (0.681; 1.350) and by MAIC was 0.864 (0.586; 1.274). ITC of Grade 3/4 AEs yielded a risk ratio (RR) of 0.81 (0.61; 1.08) for RIB vs PAL. Conclusions: Using MAIC methodology due to a lack of head-to-head trials, the resulting HRs for PFS were comparable. Similarly, using ITC, AE profiles were also comparable although the RR for AEs slightly favored RIB. Legal entity responsible for the study: Novartis Pharmaceuticals Corporation Funding: Novartis Pharmaceuticals Corporation Disclosure: A. Forsythe: Consultant for Novartis. D. Chandiwana, M. Monaco: Novartis employee and stocks/shares. All other authors have declared no conflicts of interest.

Reduction in Healthcare Resource Utilization and Costs in Patients with Chronic Myeloid Leukemia (CML) with Better Adherence to Tyrosine Kinase Inhibitors (TKIs) and Increased Molecular Monitoring Frequency

Background: More frequent molecular monitoring (qPCR tests) and higher adherence to TKIs in the management of CML have been associated with better clinical and economic outcomes. In addition, more frequent qPCR tests have been associated with better adherence to TKIs. This study estimated the overall impact of more frequent qPCR tests on healthcare resource utilization(HRU) and costs, stratified by direct (impact of qPCR test frequency on HRU and costs) and indirect (through adherence to TKIs) impacts.Methods: Adult patients newly diagnosed with CML who started first-line therapy with a TKI (imatinib, nilotinib, or dasatinib) were identified from two US administrative claims databases (2010-2015). Adherence to TKIs (using Medication Possession Ratio), number of inpatient (IP) days, emergency room (ER) visits, and days with outpatient (OP) services were measured during the first year of CML treatment. Mean costs per event (USD 2015 - payers' perspective) were estimated for each HRU component. Direct and indirect impacts of qPCR test frequency were estimated using multivariate regression models adjusting for potential confounding factors (age, sex, region of residence, health plan type, year of CML treatment initiation, Darkow disease complexity, and Charlson comorbidity index). A model was developed to assess the direct and indirect impacts of varying qPCR test frequency on HRU and costs during the first year of CML treatment under different scenarios in clinical practice. Two scenarios are illustrated: an increase i) from 1 to 2 and ii) from 2 to 4 qPCR tests.Results: A total of 1,431 patients (mean age = 54 years; 47% female) were included. During the first year of CML treatment, 36% of patients did not have any qPCR tests, 16% had 1, 15% had 2, 18% had 3, and 16% had 4 tests, for an average of 1.6 qPCR tests. The average TKI adherence level was 0.86. Holding the TKI adherence level and other variables at their mean values, the direct impact of increasing qPCR test frequency by 1 test was associated with a reduction in the number of IP days by 13.0% and ER visits by 8.3%, and an increase in the number of days with OP services by 3.0% (all p<.05). Each increase of 1 test was also associated with an increased TKI adherence level by 2.2 percentage points (p<.01). When considering the indirect impact of qPCR test frequency through adherence to TKIs, an increase of 1 qPCR test combined with an increase of the TKI adherence level by 2.2 percentage points was associated with a greater reduction of the number of IP days from 13.0% to 15.2% and ER visits from 8.3% to 8.6%, but reduced the increase in the number of days with OP services from 3.0% to 2.6%. Mean costs were estimated at $3,660 per IP day, $848 per ER visit, and $313 per day with OP services - these estimates are used for cost imputation in the Table. Thus, for a health plan of 1 million beneficiaries - considering a CML annual incidence of 1.8 per 100,000 individuals - the impact of increasing the qPCR test frequency from 1 to 2 and from 2 to 4 was associated with an estimated cost savings of $52,530 and $81,971 over a one-year period, respectively.Conclusions: More frequent qPCR tests and better adherence to TKIs was associated with a reduction of HRU events and costs for patients and payers. Efforts to increase the qPCR test frequency and adherence to TKIs stand to enhance such benefits. [Display omitted] DisclosuresLatremouille-Viau:Analysis Group: Employment; Novartis: Other: Author is an employee of Analysis Group which has received consulting fees from Novartis. Guerin:Analysis Group, Inc: Employment; Novartis Pharmaceuticals Corporation: Consultancy, Other: Annie Guerin is an employee of Analysis Group, which has received consultation fees from Novartis Pharmaceuticals Corporation. Gagnon-Sanschagrin:Novartis: Other: Author is an employee of Analysis Group which has received consulting fees from Novartis; Analysis Group, Inc: Employment. Dea:Novartis: Other: Author is an employee of Analysis Group which has received consulting fees from Novartis; Analysis Group, Inc: Employment. Cohen:Novartis: Other: Was an employee of Novartis at the time the study was conducted. Joseph:Novartis: Employment; Amgen: Other: Stocks/stock option; Pfizer: Other: Stock/stock option.

Estimating the Economic Impact of Adding Panobinostat to a U.S. Formulary for Relapsed and/or Refractory Multiple Myeloma: A Budget Impact and Cost-Benefit Model.

Multiple myeloma is an incurable B-cell malignancy with a natural history that involves alternating periods of remission and subsequent relapse. For relapsed and/or refractory multiple myeloma (RRMM), the typical patient currently receives more lines of therapy than has been feasible in the past, translating into longer progression-free survival (PFS). Consequently, cost issues have become more prominent because patients may be offered newer and more expensive therapies during a more prolonged overall treatment course. To estimate the economic impact of adding panobinostat to a U.S. health plan formulary as a treatment option with bortezomib and dexamethasone for patients with RRMM previously treated with a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), using a budget impact and cost-benefit model. Total costs of commonly used salvage therapy regimens were combined with market share data and population prevalence estimates of RRMM to yield the total cost of treatment, from the perspective of a U.S. third-party payer (commercial or Medicare) with a time horizon of 1 year. Comparator treatment regimens included bortezomib-dexamethasone, lenalidomide-dexamethasone, lenalidomide-bortezomib-dexamethasone, carfilzomib monotherapy, carfilzomib-lenalidomide-dexamethasone, and pomalidomide-dexamethasone. Costs (2015 U.S. dollars) included drug costs for oral oncology agents, medical and administration costs for injectable oncology agents, costs of adverse event (AE) prophylaxis and monitoring, and costs of grade 3/4 AEs. In a hypothetical health plan with 1 million members, the annual number of RRMM patients with previous PI and IMiD treatments was estimated at 16 and 118 for a commercial and Medicare plan, respectively. Introduction of panobinostat as part of the panobinostat-bortezomib-dexamethasone regimen was not expected to result in a substantial budget impact to either commercial or Medicare plans, with an incremental cost < $0.01 per member per month. Panobinostat-bortezomib-dexamethasone had a low cost per treated patient per month without progression, owing to the minimal increase in expenditure over existing bortezomib-based regimens and long median PFS, compared with median duration of treatment. Adding panobinostat to a plan formulary as a treatment option is expected to be cost neutral (and potentially cost saving in the context of new and more expensive treatment regimens). With a low cost per month without progression, panobinostat-bortezomib-dexamethasone represents good value for the money. Funding for this study was sponsored by Novartis, East Hanover, New Jersey. Bloudek and Kish are employees of Xcenda, a consulting company contracted by Novartis to conduct this analysis. Roy, Globe, and Kuriakose are employees of Novartis. Siegel is on the advisory boards and speaker's bureau of Celgene, Onyx/Amgen, Millennium/Takeda, and Novartis and is on the advisory boards of Merck. Jagannath is a consultant to Sanofi, Bristol-Meyers Squibb, and Celgene. Orloski is a contractor to Xcenda and provided medical writing support, which was funded by Novartis. Study design and concept were contributed by Bloudek, Roy, and Kish, assisted by Globe. Bloukek took the lead in data collection, along with Kish, and data interpretation was performed by Siegal, Jagannath, Globe, and Kuriakose. The manuscript was written primarily by Orloski, along with Roy and Kish, and revised by Roy, along with Siegal, Jagannath, Globe, Orloski, and Kuriakose.

Treatment Initiation Patterns, Modifications, and Medication Adherence Among Newly Diagnosed Heart Failure Patients: A Retrospective Claims Database Analysis.

Heart failure (HF) is a debilitating disease associated with high mortality and frequent hospitalizations. American College of Cardiology Foundation and American Heart Association (ACCF/AHA) guidelines recommend the following drug classes for HF treatment: angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor II blocker (ARB) for patients intolerant to ACEI, beta blocker (BB), and aldosterone antagonist (AA). To examine, in a real-word setting, the treatment initiation pattern among newly diagnosed HF patients in the United States, subsequent treatment modifications, hospitalizations and the impact of hospitalizations on therapy changes, and treatment adherence and persistence. Using medical and pharmacy claims data from the Truven Health MarketScan database, this retrospective cohort study included adult patients with ≥ 2 medical claims corresponding to an HF diagnosis (ICD-9-CM codes 428.x, 402.11, 402.91, 404.01, 404.11, 404.91, 404.03, 404.13, and 404.93) between April 2009 and March 2012. The date of the first claim was defined as the index date. Patients with continuous medical and pharmacy eligibility for a minimum of 12 months pre- and post-index were included in the analysis. Patients with an HF diagnosis in the 12 months before the index date were excluded. Index treatment (within 30 days post-index), subsequent treatment modification (class addition/removal) during the study period, hospitalization, and change in treatment after hospitalization (within 15 days after hospital discharge) were determined. Adherence was evaluated using the proportion of days covered (PDC) method, and persistence was defined as the proportion of patients remaining on index treatment after a defined period of time (12 months). A total of 235,758 patients meeting the sample selection criteria were included in the analysis and were followed for a median of 28 months after the index date. Approximately 42% of patients were not prescribed any HF-specific treatment within 30 days post-index. Among those treated, prescriptions for ACEIs were filled by 46.42% of patients, ARBs by 17.07%, BBs by 75.62%, and AAs by 9.83%. Based on HF therapy class, monotherapy was prescribed to 51% of patients, bi-therapy to 40%, and triple therapy to 9%. More than 80% of patients experienced treatment modification during the median 28 months of follow-up. A total of 174,563 (74.0%) patients had at least 1 all-cause hospitalization (mean 1.11 [SD = 0.98]) per year, with a mean length of stay (LOS) of 7.19 [SD = 8.69] days. Within 12 months post-index, 85.7% of these patients experienced an all-cause hospitalization, with 29.6% having HF-related hospitalization (mean 0.18 [0.36]) and mean LOS of 5.85 [5.45] days. More than 60% of patients continued on the same therapy after all-cause or HF hospitalization. More patients on multiple therapies remained on the same treatment (73%-89%) compared with those treated with monotherapy (60%-73%) after the first HF hospitalization. Among patients untreated before hospitalization, 9.8% and 17% received treatment after all-cause and HF hospitalization, respectively. During the entire study period (median 28 months), 29% of patients did not have a prescription fill for HF-specific treatments. The median PDC was > 0.65, and considering a gap of 30 days between ends of supply from 1 medication fill to the subsequent fill, persistence ranged from 41% (AA) to 52% (BB). Findings of this claims database analysis among 235,758 HF patients suggest that more than one third of newly diagnosed HF patients do not receive HF-specific medication within 30 days following initial diagnosis. Despite ACCF/AHA recommendations of initiating treatment with a combination of 2 HF drug classes, only 40% of patients had a prescription fill for bi-therapy. Hospitalization did not have a major impact on HF therapy prescribing patterns. To our knowledge, this is the first study to establish the impact of hospitalization on HF-specific treatment among newly diagnosed patients. Adherence and persistence were moderate across all HF therapies of interest. This analysis reveals the need for further research to better understand the reasons for the demonstrated delay in HF treatment initiation and limited use of guideline-directed medical therapy after initial diagnosis. This study was funded by Novartis Pharma AG, Basel, Switzerland. Deschaseaux, McSharry, Hudson, Agrawal, and Turner are permanent employees of Novartis. Concept and study design were contributed by Deschaseaux, Hudson, and Turner, along with McSharry. McSharry took the lead in data collection, along with Deschaseaux, Hudson, and Turner. Data interpretation was performed by Hudson, along with the other authors. The manuscript was written by Agrawal, along with Deschaseaux and Turner, and revised by Deschaseaux and Turner, along with the other authors.

Pulmonary Function and Rescue Medication Use in Patients Receiving Omalizumab in Real World Settings: A Systematic Literature Review of Nonrandomized Studies

SESSION TITLE: Allergy and Airway Posters SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PM PURPOSE: The objective was to provide a summary of the real-world clinical and health economic outcomes associated with omalizumab in the treatment of moderate to severe allergic asthma. METHODS: A systematic literature review was conducted to identify studies of omalizumab in patients ≥12 years with moderate to severe allergic asthma. A search of MEDLINE and EMBASE reference databases was conducted for relevant studies published from 2003 to 2014. Outcomes of interest included rescue medication use and pulmonary function assessments (FEV1, FVC, and PEF). Patient-reported outcomes (PROs) were also reviewed for included studies. Study quality was assessed by 2 reviewers using the Newcastle-Ottawa Quality Assessment Scale of Cohort Studies and the International Society of Pharmacoeconomics and Outcomes Research checklist. RESULTS: A total of 42 studies were included; 20 studies evaluated pulmonary function and 9 evaluated rescue beta-agonist use. Statistically significant improvements in FEV1 were reported in 75% (15/20) of included studies. Improvements in FEV1 ranged from 3.2%-43.6%. Five studies reported changes in FVC or FEV1/FVC. Significant improvements in FVC were observed in 3 studies and in FEV1/FVC in 2 studies. Six studies analyzed PEF with 5 finding significant improvements. Seven studies reported significant reductions in rescue medication use. The percentage of patients with any rescue medication use ranged from 87.0%-97.7% at baseline to 12.5%-49.8% at follow-up. In studies examining change in use from baseline, change at follow-up ranged from 56.1%-78.8%. Among the included studies, 14 utilized patient-reported health-related quality of life (HRQoL) outcomes. The ACT (12 studies) and the AQLQ (4 studies) were the most commonly used surveys to assess asthma control and HRQoL, and improvements were consistently seen after omalizumab was added to therapy. CONCLUSIONS: While patient populations and outcome definitions are heterogeneous, overall, patients with moderate to severe asthma using omalizumab had improvements in FEV1 and PEF and experienced a decrease in the need for rescue beta-agonist medications. Patient-reported asthma control and HRQoL appears to improve among patients utilizing omalizumab in clinical settings. CLINICAL IMPLICATIONS: Asthma patients administered omalizumab during routine clinical use experience significant clinical benefits, including an improvement in pulmonary function and decrease in rescue medication usage. DISCLOSURE: Jonathan Corren: Consultant fee, speaker bureau, advisory committee, etc.: Consultant to Novartis Susan Gabriel: Employee: Novartis Employee Tom Karagiannis: Employee: Novartis employee Kimberly Ruiz: Consultant fee, speaker bureau, advisory committee, etc.: Consultant to Novartis Bethany Sawchyn: Consultant fee, speaker bureau, advisory committee, etc.: Consultant to Novartis Jennifer Colby: Consultant fee, speaker bureau, advisory committee, etc.: Consultant to Novartis Meryl Mendelson: Employee: Novartis employee No Product/Research Disclosure Information

Buparlisib (Bkm120) in Patients with Pi3K Pathway-Activated, Metastatic Non-Small Cell Lung Cancer (Nsclc): Results from the Basalt-1 Study

ABSTRACT Aim: In vitro, NSCLC cell lines with PIK3CA mutations have shown increased sensitivity to the oral pan-PI3K inhibitor buparlisib (BKM120). BASALT-1 is an open-label, two-stage, Phase II study to assess the safety and efficacy of buparlisib in patients (pts) with pre-treated metastatic NSCLC (squamous [sq] and non-squamous [non-sq] histology) and activated PI3K pathway (NCT01297491). Here we report results from the Stage 1 futility analysis (FA) for each histology. Methods: Pts (≥18 yrs) with previously treated, metastatic NSCLC (sq or non-sq histology) with activated PI3K pathway (defined as PIK3CA mutation and/or PTEN mutation and/or PTEN-negative staining [ Results: Thirty pts had been treated in each histologic group at the time of FA (>1200 pts screened). In the sq group, 21 pts were male (median age: 65.5 yrs); in the non-sq group, 19 pts were male (median age: 62.0 yrs). Median treatment exposure was 6.9 (sq group) and 7.2 (non-sq group) wks. Median PFS was 2.79 (95% CI: 1.38, 4.11) and 2.69 (95% CI: 1.41, 2.89) months for the sq and non-sq groups, respectively. PFS rate at 12 wks was 23.3% (95% CI: 9.9, 42.3) for the sq group and 20.0% (95% CI: 7.7, 38.6) for the non-sq group. Best overall responses (RECIST 1.1): partial response (1 pt [3.3%] in each group), stable disease (14 pts [46.7%] in each group), progressive disease (7 pts [23.3%] sq / 9 pts [30.0%] non-sq), unknown (8 pts [26.7%] sq / 6 pts [20.0%] non-sq). Most common (≥30%) AEs possibly related to study drug: hyperglycemia (36.7%), pruritus (33.3%), diarrhea (30%), and nausea (30%) for sq, and asthenia (30%) for non-sq. Conclusions: In this PI3K pathway-activated group of NSCLC pts, the futility criterion in Stage 1 was met in both histology groups. Thus, enrollment of Stage 2 was not initiated. Results of this study are in line with previous observations where single agents targeting the PI3K pathway have shown marginal activity. Studies of buparlisib in combination with docetaxel in pts with sq NSCLC are ongoing. Disclosure: J. Soria: - Research funds from Novartis (Instititution) - Compensated advisory board Novartis F. Grossi: Novartis advisory board; E. Felip: Advisory Board: BI, Novartis, Roche, BMS, Lilly; M. Thomas: AD-Board honoraria: Novartis, Roche, Lilly, BMS Speaker honoraria: BMS, Lilly; P. Roussou: - Novartis employee - Shares in Novartis; G. Atalla-Vidam: Novartis employee; P. Aimone: Novartis employee. All other authors have declared no conflicts of interest.

451PD - Phase I Study of the Pi3K&Agr; Inhibitor Byl719, As a Single Agent in Patients with Advanced Solid Tumors (Ast)

ABSTRACT Aim: BYL719 is a selective oral inhibitor of the Class l PI3K a-isoform. PI3Ka is encoded by PIK3CA, a frequently altered gene in human cancers. This was a Ph I, dose-escalation and -expansion, first-in-human study of BYL719 in pts with PIK3CA-altered aST, or PIK3CA-altered or wild-type (wt) ER+ breast cancer (BC) (NCT01219699). Methods: Adult pts with advanced PIK3CA-altered (mutation or amplification) aST received oral BYL719 QD or BID (28-day cycles). Pts with PIK3CA wt ER+ BC were also enrolled into the dose expansion. A Bayesian logistic regression model with overdose control guided dose escalation. Primary objective was to determine MTD and/or RP2D of single-agent BYL719. Safety (CTCAE v4.0), tolerability, PK, preliminary efficacy (RECIST) were also assessed. Results: As of Mar 10, 2014, 132 pts received BYL719 QD (30–450 mg) or BID (120, 150, 200 mg). Median exposure was 11.9 (0.4–98) wks. DLTs were reported in: 4 pts (hyperglycemia x2, nausea x2) at 450 mg QD, 4 pts (hyperglycemia x4) at 200 mg BID, and 1 pt (hyperglycemia and hypophosphatemia) at 150 mg BID. BYL719 QD MTD is 400 mg (and was used for dose expansion); here, BYL719 BID MTD is declared as 150 mg. Most common (≥20%) suspected study drug-related all-Grade AEs at the MTDs were: BYL719 150 mg BID (n = 15) – hyperglycemia, nausea (both 53%), diarrhea, decreased appetite, fatigue, stomatitis (all 33%); and BYL719 400 mg QD (n = 63 including dose expansion) – hyperglycemia (51%), nausea (48%), diarrhea (41%), decreased appetite (38%), fatigue (32%), vomiting (30%), rash (20%). Overall, 15 of 131 evaluable pts had partial responses (PRs; incl. 2 [out of 24 pts] with PIK3CA-altered ER+ BC); 7 PRs were confirmed: 2 at 270 mg QD, 1 at 350 mg QD, 2 at 400 mg QD, 2 at 150 mg BID. Disease control rates (CR, PR, or SD) at MTDs were: BYL719 400 mg QD – 53%; and BYL719 150 mg BID – 67%. Median PFS at ≥270 mg in ER+ HER2– BC (n = 21) was 166 days. In pts with PIK3CA wt ER+ BC (n = 5) duration of exposure range was 7–61 days; no PRs were observed in wt pts. Conclusions: BYL719 is the first a isoform-specific PI3K inhibitor to show single-agent responses in tumors with activating mutations. The safety profile was favorable with mostly on-target effects (i.e. hyperglycemia). Data comparing PIK3CA-altered and wt ER + /HER2– BC pts will be presented. Disclosure: D. Juric: I have participated on scientific advisory board meetings for Novartis. No other conflicts of interest; M. Schuler: Ad Board/Consultant (Compensated): AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer Research grants: Boehringer Ingelheim, Novartis Honoraries for CME lectures: Alexion, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Lilly, Novartis, Pfizer; J. Berlin: Vanderbilt Cancer Center receives research support from Novartis for this trial. I personally do not receive funding; R. Seggewis-Bernhardt: I have been on the Novartis' advisory board meeting \From bench to bed - Anforderungen an Translationale Konzepte\, 5 & 6 March 2014 in Basel, Switzerland; J. Rodon: Attendance as consultant to a Novartis Advisory Board that was compensated; J. Tabernero: Consultant or advisory role: Amgen, Imclone, Lilly, Merck KGaA, Millennium, Novartis, Roche, Sanofi, Celgene, Chugai and Taiho; F. Janku: I have research funding from Novartis; H.S. Rugo: I received Research Support on behalf of my university to conduct trials from Novartis. I have received travel support from Novartis; D. Bootle: I am an employee of Novartis, C. Quadt: I am employee of Novartis Oncology and own Novartis shares; C. Coughlin: I am an employee of Novartis; D. Demanse: I have an employment to disclose: Statistician at Novartis; L. Blumenstein: I am an employee of Novartis. All other authors have declared no conflicts of interest.