TREAT-NMD and the Role of the Industry in Orphan Diseases Dr. Stefanie Possekel Santhera Pharmaceuticals
TREAT-NMD EU-funded infrastructure to accelerate therapy development in neuromuscular diseases Clinical and basic research Clinical networks Patient and parent organisations Industry
TREAT-NMD in a nutshell EU network aiming at overcoming fragmentation and speeding up treatment development for neuromuscular diseases (NMDs), with DMD and SMA as primary focus 22 partners in 11 countries involved started in 2007, funded for 5 years First achievements after one year: # Assessment of current animal models # EuroBioBank # International Collaborations were established # The Clinical Trials Coordination Center # Network in action - DMD # Network in action - SMA # Ethical and regulatory issues # Patient registries (without involvement of SME partners) DMD: Duchenne Muscular Dystrophy, SMA: Spinal Muscular Atrophy
The diseases: DMD and SMA Duchenne Muscular Dystrophy (DMD) Most common form of muscular dystrophy Affects motor skills, results in muscle loss and skeletal deformities, leads to respiratory failure and cardiac complications Average onset between 3 and 5 years; average life expectancy today between 30 and 35 years Affects males of all ethnicities Spinal Muscular Atrophy (SMA) Group of diseases which affect the motor neurons of the spinal cord and brain stem Patients either do not acquire or eventually lose the ability to move, will suffer from fatal respiratory insufficiency Affects all racial and ethnic groups Leading genetic cause of mortality in infants and toddlers ~ 30,000 patients with DMD, SMA each worldwide, as compared to ~ 1 million patients with multiple sclerosis or 350,000 new cases of prostate cancer each year EU only
Industrial partners of the network clinical program in DMD preclinical program in DMD preclinical activities in DMD and SMA discovery programs in SMA genetherapy approaches for DMD and other NMDs evaluation of biotherapeutic products for DMD and SMA and associated industrial members of TREAT NMD: preclinical activities in Muscular dystrophy clinical program in DMD clinical program in SMA preclinical program in DMD clinical program in DMD clinical program in DMD discovery programs in DMD and SMA only little involvement of Big Pharma: Wyeth, Novartis, Genzyme
Industry & academia: complementary & synergistic alliance academia industry Understanding the disease: molecular level cellular level ++++ + +++ ++ ++ ++ + organ level Discovery of potential drug targets Discovery of new therapies Development of new therapies Formal Requirements Costs ++++ Sponsor
Role of industry Focus to bring a drug to the market Collaborations/ in-licensing with academia Introduction of Standard Operating Procedures Expertise in Chemical Manufacturing Control Expertise in clinical development, including regulatory affairs Expertise in distribution and marketing Proof that there is a business case behind orphan drugs Encouragement of more companies to direct research into this field Note: There is an increasing support for SMEs/ for-profit organizations through patient organizations and charities
Orphan drug regulations Registered Orphan Drugs (USA) WHO: there are more than 5000 rare diseases (i.e. generally < 10 patient / 10k population) most of them with too few patients to develop commercially viable treatments 300 USA was the first country with an Orphan Drug (OD) legislation (1983) providing incentives to develop drugs for such diseases 250 200 150 Following countries implemented OD legislation since then: Japan (1993), Australia (1998), EU (2000; 41 Market Authorization Applications (MAA) granted thereof less than 50% based on double blind, placebo controlled trials) Orphan Drug status provides market exclusivity and other incentives 100 50 0 Prior 1983 2007
Examples for orphan drug regulations Country Definition of OD Market Exclusivity Other Incentives USA Less than 200,000 patients (~7.5 / 10k) - or any disease where drug development does not provide a positive Return of Investment (ROI) 7 years Tax credit up to 50% of total costs (even for unsuccessful trials), study design assistance, eventually trial funding EU Less than 5 / 10k - or any disease where drug development does not provide a positive ROI 10 years (reviewed after 5 years if criteria still valid) Free pre-submission meetings with EMEA; 50% reduction in fees for all steps of obtaining MAA Less than 50,000 (~ 4/10k) registration validity period of 10 years instead 6 for other products Fast track MAA Free advice and pre-submission mtgs; Some funding available; up to 50% reimbursement of dev-costs plus some tax reductions (central procedure) Japan MAA: Market Authorization Application
EMEA Guideline on clinical trials in small populations Introduced February 1, 2007 Facilitates approval of product candidates developed to treat diseases affecting only a small number of patients a single clinical trial with limited data can justify for market approval p-values of 0.05 not necessarily required due to small population pre-selection of primary endpoint not necessarily required if clinical studies can be judged on overall effect
Orphan indications can be a successful Business Model Companies with main business in orphan drugs Current orphan drug brands from major Pharma in Europe Celecoxib (Onsenal, Pfizer) Dasatinib (Sprycel, Bristol-Myers-Squibb) Deferasirox (Exjade, Novartis) Iloprost (Ventavis, Schering) Imatinibmesilat (Glivec, Novartis), Pegyisomant (Somavert, Pfizer) Rufinamide (Inovelon, Eisai Limited) Sildefanil (Revatio, Pfizer) Sunitinib (Sutent, Pfizer) Ziconotid (Prialt, Eisai) and future drugs to come SNT-MC17 (Santhera/Takeda) However, there are more than 5000 identified orphan diseases with no or (limited) treatment
A Difficult task needs a joint effort... NO approved treatment for either DMD nor SMA nor any other muscular dystrophy Designing clinical trials in small populations of patients with a chronic progressive diseases is very difficult Joint effort of researchers, clinicians, patient/parent organization and industry is needed to succeed to TREAT-NMD Thanks to the EU for funding the Network and thanks to AFM and all other patient/parent organization for their tremendous effort and support.