biologics in asthma: generics, reimbursement, and market potential

Evolving treatment landscape in asthma: Biologics, Generic combination inhalers, Reimbursement, and Market Restrictions Moderator today:

Christina Vasiliou – Senior Immunology & Inflammation Analyst

Pharma intelligence | informa 2

Overview

Disease overview

• Diagnosis, risk factors, prevalence

• Patient segmentation

Treatment

• Guidelines

• Prescribing trends

Market forecast: 2015-24

• Methodology

• Overall market size by country

• Generics of key combination inhalers

• Entrance of new biologics

• Reimbursement and market access restrictions

Conclusions and summary


Disease overview


Disease definition and diagnosis

Asthma definition

• Chronic respiratory disease

• Recurrent breathlessness and wheezing

• Asthma attacks vary in frequency and severity

Diagnosis

• No gold standard in diagnosing asthma

• Bronchial challenge test and spirometry

• Reversibility test to distinguish asthma from COPD

• High rate of undiagnosed cases within milder groups

Risk factors

• Genetic factors

• Environmental factors

• Dietary changes and obesity


Asthma prevalence

Total diagnosed prevalent cases of current asthma in the US, Japan, and five major EU markets, 2014–34

Source: Datamonitor Healthcare; Célant et al., 2014; Centers for Disease Control and Prevention, 2015; De Marco et al., 2012; Fukutomi et

al., 2011; Kusunoki et al., 2009; Organisation for Economic Co-operation and Development, 2012; Robert Koch-Institut, 2014a, 2014b; Health

and Social Care Information Centre, 2011; United Nations Population Division, 2013


Patient segmentation: Intermittent asthma makes up nearly half of diagnosed cases

Severity of diagnosed asthma patients in the US, Japan, and five major EU markets (%), 2015

Source: Datamonitor Healthcare’s Epidemiology: Asthma, 2015


Treatment


Treatment: Guidelines recommend step-up treatment

• Multiple drug classes are approved for the treatment of asthma

SABA as-needed with no controller

Regular low-dose ICS plus as needed SABA

Low-dose ICS/LABA as maintenance treatment plus as-needed SABA

Medium-dose ICS/LABA as maintenance plus as-needed SABA

Refer for expert investigation and add-on biologic treatment, such as omalizumab

Step 1 Step 2 Step 3 Step 4 Step 5

ICS = inhaled corticosteroid; LABA = long-acting beta 2 agonist; LAMA = long-acting muscarinic antagonist; OCS = oral corticosteroid; SABA = short-acting beta 2 agonist

Source: GINA, 2015

Add-on LAMA; OCS


Prescribing trends: US asthma treatment tree

US asthma treatment tree

Source: Datamonitor Healthcare’s proprietary asthma survey, April 2015


Prescribing trends: Drug dynamics in the US

US drug use in asthma, by severity



Market forecast: 2015-24


Market forecast: Methodology

Epidemiology: diagnosed current asthma (by country)

Intermittent Mild persistent Moderate persistent

Severe persistent

% Seeking maintenance treatment

% Drug-treated

Baseline brand penetration

Compliance

Cost/year

Total annual sales/brand

Market events

Source: Datamonitor Healthcare


Market forecast: Overall market size by country

Key drivers of market growth

• Increasing asthma prevalence in the US

• Annual price increases of branded therapies in the US

• New biologic launches

Key resistor to market growth

• Arrival of ICS/LABA generics

Asthma sales in the US, Japan, and five major EU

market, by country ($m), 2015-24



ICS/LABA class: Key brands face generic competition…

Advair generics are available in the EU and on track to launch in the US

• DPI: AirFluSal Forspiro (Sandoz and Vectura) received EU approval in Q4 2013

• Launched in Germany and the UK in Q2 2014 and Q4 2015, respectively

• pMDI: Cipla launched Serroflo, in Germany in Q3 2014; Mylan launched Sirdupla in the

UK in Q2 2015

• FDA accepted Mylan’s ANDA for generic DPI in Q1 2016, providing a GDUFA goal date

of March 2017

Symbicort generics are available in the EU

• DPI: DuoResp Spiromax (Teva) launched in Germany and the UK in 2014

• Orion filed Bufomix Easyhaler for EU marketing authorization in Q1 2013

• Vectura and Sandoz are developing VR632

• DPI and pMDI: later arrival expected in the US


…but generic inhalers have had limited uptake to date in the EU

Limited substitutability for branded inhalers

• Lack of automatic substitution of inhaled ICS/LABA combinations in Europe

• In France, each new branded generic inhaler is assessed by the Transparency

Commission as a new me-too product

Physician and patient reluctance to switch devices

• Concerns over dose and efficacy equivalence

• Switching will only be successful if costly change management switching programs

are implemented

Minimal price discounts

• Not sufficient to switch

• Country- and device-specific discounts


In the US, higher rates of generic inhaler adoption are anticipated

US payers will incentivize use of generic inhalers through formulary management

given sufficient discounts

• If ≥20% discount to brand, step therapy requirements and co-pay differentials will be

enforced

Switching of existing patients will not be enforced

As in the EU, physicians and patients will be reluctant to switch devices

• However, out-of-pocket differences will have a persuasive influence on physicians and

patients


Despite generic competition, Advair and Symbicort will remain commercially successful


Inhaler products market share in the US, Japan, and five major EU markets (%)


Competition in the biologics class is increasing

Drug Company Mechanism of action

Indication Formulation Dosing frequency

US EU Japan

Xolair (omalizumab)

Roche/Novartis Anti-IgE monoclonal antibody

Treatment of moderate to severe persistent asthma in patients 12 years of age and above, who have a positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled corticosteroids.

SC 150 to 375mg every 2 or 4 weeks

2003 2005 2009

Nucala (mepolizumab)

GlaxoSmithKline IL-5 antagonist monoclonal antibody

US: Add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype EU: Add-on treatment for severe refractory eosinophilic asthma in adult patients

SC 100mg once every 4 weeks

2015 2015 2016

Cinqair (reslizumab)

Teva IL-5 antagonist monoclonal antibody

Add-on maintenance treatment of patients with severe asthma aged 18 years and older, and with an eosinophilic phenotype

IV 3 mg/kg once every four weeks

2016 MAA n/a



Several IL-inhibitors are moving through the pipeline

Drug Company Mechanism of action

Formulation Phase

benralizumab AstraZeneca Anti-IL-5 receptor α monoclonal antibody

SC III

Cinqair (reslizumab) Teva IL-5 antagonist monoclonal antibody

SC III

dupilumab Sanofi/Regeneron Anti-IL-4/IL-13 monoclonal antibody

SC III

lebrikizumab

Roche/Chugai Anti IL-13 monoclonal antibody

SC III

tralokinumab AstraZeneca Anti IL-13 monoclonal antibody

SC III



Payers fear budget impact of IL-5 inhibitors

Payers cautiously optimistic about role of IL-5s in asthma but budget impact is a worry

• Payers recognise potential benefit but highlight biologics only address a limited population

subset

• Endpoints chosen (reduction in asthma exacerbations, hospitalizations, ER visits) are relevant

but concerns remain about high cost

• Concerns over potential overprescribing

Payers and KOLs unclear about place in treatment pathway

• Patient overlap between Xolair and new IL-5s

• Payers unable to accurately project budget impact of IL-5s

• Epidemiological studies and forecasts expected to influence price negotiations


Stringent access controls to IL-5 inhibitors in all markets

US payers are implementing strict prior authorization criteria for IL-5 inhibitors

• Physician recommendation is sufficient for most payers but some plans may require

documented evidence of eosinophil count

• Earlier access is unlikely

• ICER deemed Nucala over-priced based on annual treatment cost of $32,000

• Lack of long-term efficacy data

• More likely to be cost-effective at $7,800-12,000 annual cost

EU payers will use Xolair’s price as benchmark for IL-5s

• Nucala expected to be priced on par or below Xolair

• Access controls on Nucala modelled on experience with Xolair

• Registries, therapeutic plans, outcome-based risk sharing, patient access schemes

• Biologic use reserved to specialist hospital centres

• Further scrutiny of clinical trial results and assessment of benefit in specific patient groups


Entrance of new anti-IL biologics pivotal to market growth


Sales of biologic products in the US, Japan, and five major EU markets, by country ($m), 2015-24


Benralizumab expected to see the greatest uptake


Sales of benralizumab in the US, Japan, and five major EU markets, by country ($m), 2015-24


Nucala will have a

dominant position until

benralizumab is

launched

Sales of Cinqair in the US, Japan, and five major EU markets,

by country ($m), 2015-24

Cinqair’s IV formulation and more restrictive US label will impact its potential



Concerns over lebrikizumab’s clinical trial data

• Periostin biomarker

• Efficacy and safety assessed in two identical, randomized, multicentre, placebo-

controlled Phase III studies (LAVOLTA I and II) in patients with severe, uncontrolled

asthma

• Primary endpoint: rate of asthma exacerbations over 52 weeks

• Endpoint evaluation based on people with high periostin levels or blood eosinophils

• Only LAVOLTA I met its primary endpoint

• KOLs consider its efficacy significantly lower than IL-5 inhibitors

Further interpretation and analysis required


Summary

Biologics drive positive growth during 2015-24

• Potential to address high burden in asthma

• Prescribing will be restricted due to high cost

• Payers concerned about overprescribing

• Strict access controls

Key ICS/LABAs facing generic competition

• Limited uptake to date in Europe

• Higher rates of adoption expected in the US

• Advair and Symbicort will remain commercially

successful


Finding Datamonitor Healthcare’s asthma content

Thank you very much for joining us today. If you have any further questions or comments, please email them to [email protected]

biologics in asthma: generics, reimbursement, and market potential

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