SESSION VI THE CHALLENGE OF NEW TREATMENTS THE PHARMA INDUSTRY

Size: px
Start display at page:

Download "SESSION VI THE CHALLENGE OF NEW TREATMENTS THE PHARMA INDUSTRY"

Transcription

1 SESSION VI THE CHALLENGE OF NEW TREATMENTS THE PHARMA INDUSTRY Bruno C. Musch, MD PhD Baveno, Italy November 30th, 2013

2 DISCLOSURE OF INTEREST Dr.Musch is currently Medical Director in GENENTECH/Roche, he worked for Merck Serono, Pfizer, Pharmacia, Upjohn, Rhone- Poulenc and Synthelabo, he has been consulting for Shire, Actelion, Xenoport, GeNeuro, Aventis, Novartis, Boehringer Ingelheim

3 HISTORY OF MS DRUG DEVELOPMENT & COMMERCIALIZATION

4 The history of drug TYSABRI treatment in ms NEW INJECTABLES/ NEW CELL TARGETS 2004 ORALS-II 2013 ORALS-I 2010 GYLENIA PPMS?? LEMTRADA AUBAGIO/TECFIDERA More choices Therapeutic Strategies Personalized medicine First line/ Second line/risk-benefit Regulatory environment more conservative High efficacy threshold ABCR unchallenged New Labels COPAXONE 1996 INTERFERONS 1993 Evolution of diagnostic criteria (From Poser to McDonald criteria) Low frequency high frequency/nab Orphan drugs

5 MS DRUG DEVELOPMENT & COMMERCIALIZATION PROCESS

6 MS DRUG DEVELOPMENT PROCESS -1 Molecular Discovery Animal Testing Low predictivity PHASE I PK/PD Tolerability Safety Profile Need testing in patients Personalized Medicine Biomarkers PHASE II Dosing Profile MRI Predictivity

7 MS DRUG DEVELOPMENT PROCESS - 2 KEY DECISION POINT Unmet medical need Likelihood of success Differentiation Value proposition Feasibility PHASE III Benefit/Risk profile Population End Points Study Design Personalized Medicine Biomarkers Responders/Non responders Profile T I M E POST APPROVAL PHASE IV REMS Registries Real World Experience Long Term use Life cycle management

8

9 The Name of the Race BENEFIT/RISK ppersonalize DIDIFFERENTIATION

10 Table 4: NEW MS DRUGS: Placebo (or Rebif) controlled Phase III studies Effect on Annualized Relapse Rate (ARR) and Confirmed Disability Progression (CDP) STUDY PTS N. DOSE ARR RELATIVE REDUCTION TECFIDERA DEFINE mg bid 240mg tid TECFIDERA CONFIRM mg bid 240 mg tid 53% 48% 44% 51% CDP RELATIVE RISK REDUCTION 38% (S) 34% (S) 21% (NS) 24% (NS) GILENYA FREEDOMS mg/day 54% 17.7%vs24%( S) GILENYA FREEDOMS ,5mg/day 48% 17% (NS) AUBAGIO TEMSO mg/day 14mg/day AUBAGIO TOWER mg/day 14mg/day 31% 31% 23.7% (NS) 29.8% (S) 22.3% 36% 31.5% (S) LAQUINIMOD ALLEGRO mg/day 23% (NS) 11%vs15% (S) LAQUINIMOD BRAVO mg/day 21% (NS) 33.5% (S) LEMTRADA CARE MS I 581(naives) vs Rebif 55% (S) 38 % (NS) vs Rebif LEMTRADA CARE MS II 840 Vs Rebif 49% (S) 42 % (S) vs Rebif

11 In the Near Future, a Variety of MS Therapeutics with Diverse MOAs Will Be Available Pegylated IFN Natalizumab (PMS) Daclizumab Alemtuzumab Ocrelizumab (relapsing MS, PPMS) Fingolimod in PPMS? 11

12 GENERAL CONSIDERATIONS ON PERSONALIZED HEALTH CARE

13 PERSONALIZED HEALTH CARE It is more important to know what sort of person has a disease than what sort of disease a person has

14 PERSONALIZED HEALTH CARE NEW PARADIGM ONE SIZE FITS ALL The wrong drug for 50 % of patients PERSONALIZED MEDICINE The power of right The right drug for the right patient The right dose for the right patient The right dose schedule for the right patient The right time to treat The right benefit /risk ratio. The right benefit. Optimize benefit /risk Maximize value (cost) Highly differentiated drugs Clearly defined benefit

15 PERSONALIZED MEDICINE CONTRIBUTORS & TOOLS DISEASE BIOLOGY & HETEROGENEITY DRUG PROPERTIES & PROFILE DIAGNOSTIC TOOLS PERSONALIZED MEDICINE BIOMARKERS PROGNOSTIC FACTORS RESPONSE TO TREATMENT: Yes/no RISK OF TREATMENT : Low/high

16 THERAPEUTIC STRATEGIES IN MS

17 REDIFINE THE DISEASE / MS DISEASE ENVIRONMENT RELAPSING M S EARLY STAGE MID STAGE LATE STAGE CIS CDMS/RRMS SPMS SPMS Relapsing Non relapsing good prognosis Less severe Slow progression bad prognosis High Disease Activity Rapidly Evolving Severe Fast progression Treatment failures PRIMARY PROGRESSIVE MS

18 CIS RRMS SPMS PERSONALIZED DRUGS TO TREAT EARLY PROGNOSTIC FACTORS BIOMARKERS E A R L Y Escalation strategy DISEASE STAGES

19 THERAPEUTIC STRATEGIES IN MS ESCALATION EARLY AGGRESSIVE INDUCTION COMBINATION PERSONALIZED MEDICINE Patient monitoring Definition of response over time Patient-centric management Convenience Safety monitoring PREDICT PREVENT

20

21 DRUG DEVELOPMENT KEY POINTS PATIENT POPULATION: DESIGN: Patient selection Sample size Pre-established subgroups (possible personalization) Adequate and well controlled Duration Comparator Statistical plan Adaptative design

22 ADEQUATE AND WELL CONTROLLED STUDIES (FDA) A design that permits a valid comparison with a control to provide a quantitative assessment of drug effect Adequate measures are taken to minimize bias on the part of the subjects, observers and analysts of data Methods of assessment of subjects response are well defined and reliable An analysis of the results of the study adequate to assess the effect s of the drug

23 CLINICAL STUDY END POINTS & OUTCOME ASSESSEMENT GENERAL PRINCIPLES: MS SPECIFIC END POINTS: Subjective/Objective Sensitivity to clinically meaningful changes Reproducibility Timing of assessment Quantitative versus qualitative metrics Relapses Disability progression Lesions (MRI) Composite metrics ( DAFS) Patient Reported Outcomes (PRO) Cognitive end points Pharmacoeconomic end points

24 Clinical studies in MS Efficacy End Points RELAPSES All these end points are highly correlated MRI LESIONS KEY OUTCOMES DISABILITY PROGRESSION COGNITION PATIENT REPORTED OUTCOMES RELEVANT OUTCOMES HEALTH ECONOMIC OUTCOMES

25 25

26 CLINICAL SIGNIFICANCE CO-PRIMARY OUTCOMES (see AD) INCREMENTS OF STATISTICAL RELEVANT CHANGE CORRELATES WITH CHANGES IN CLINICAL RELEVANT ANCHORS FDA GUIDELINES ON PATIENTS REPORTED OUTCOMES Benedict & Walton: MSJ, 2012

27 RISK ASSESSMENT OF MS DRUGS

28 FDA AMENDEMENT ACT FDAAA FDA may require sponsors to submit a proposed REMS if it is determined that a REMS is necessary to ensure that the benefits of the drug outweigh the risks REMS = Risk Evaluation and Mitigation Strategy 2009 FDA REMS Draft Guidance Document

29 Potential REMS Elements Medication Guide Communication Plan Elements to Assure Safe Use (ETASU) Implementation System (ETASU only) Timetable for Submission of Assessments (all) Patient information highlighting risks Must be distributed with each new prescription and refill Plan for informing HCPs or stakeholders on risks Controlled system to enforce appropriate use (e.g., certification, registry, restricted drug distribution) Steps to monitor and evaluate implementation of the ETASU Frequency of REMS performance assessments; min freq required by FDA is 18 months, 3 yrs, and 7 yrs post-approval

30 THE LABEL LANDSCAPE AB(C)R GYLENIA (USA) TYSABRI (USA/EMA) GYLENIA (EMA) indicated for the treatment of patients with relapsing forms (relapsing remitting) of multiple sclerosis to decrease the frequency of clinical exacerbations and delay the accumulation of physical disability SECOND LINE (inadequate response/ Highly active/rapidly Evolving Severe (Black Box for PML) AUBAGIO/ TECFIDERA LEMTRADA (EMA) indicated for the treatment of patients with relapsing forms (relapsing remitting ) of multiple sclerosis indicated for adult patients with relapsing remitting multiple sclerosis (RRMS) with active disease defined by clinical or imaging features, not recommended for patients with inactive disease or those stable on current therapy..

31 LEMTRADA EPAR* The CHMP was of the view that this indication would avoid restricting alemtuzumab to patients with high disease activity only. Thus, such approach was seen as allowing for disease modification also for patients, whose disease course is not yet highly active, but is still disabling or likely to become highly active or may later result in higher cumulative disability. The CHMP concluded that this indication, when read in conjunction with the entire physician and patient documentation, would facilitate a more individualized treatment decision for a given patient by the prescribing specialist neurologist, while at the same time preventing treatment of patients with inactive disease (benign course) or those stable on an alternative treatment. * European Public Assessment Report

32