2014 REPORT
3 affects an estimated 1.5 million an estimated affects American adults; ligaments, the muscles, affects Approximately and bones. tendons, 15 million adults report are that they perform some common unable to activities the pain; due to of arthritis, mon form which affects million Americans; and 27 nearly matory arthritis, which affects of people percent 30 approximately with psoriasis. The development of new, innovative innovative of new, development The not be possible would therapies without the patients who volunteer participateto in clinical trials. for in development medicines The 92 arthritis include: • arthritis rheumatoid 55 for which • pain which musculoskeletal 15 for • osteoarthritis,10 for the most com- am- • psoriatic arthritis,7 for an infl participate. Another 58 are ongoing ongoing participate. Another 58 are patients. new but not recruiting 2 1 , search performed , search www.clinicaltrials.gov 7/14/2014. Search criteria: arthritis, States, United Search 7/14/2014. 1, 2, 3; industry only. Phase 0, Source: 2003 Medical Expenditure Survey, CDC Survey, 2003 Expenditure Medical 2003 National Health Interview Survey, CDC Interview 2003 National Health Survey, 2 3 1 The CDC also estimates that muscu- the American cost diseases loskeletal $128 billion annually in direct economy such as costs and indirect costs medical and productivity. lost wages companies research Biopharmaceutical to medicines 92 developing currently are help the millions of Americans affected either are These medicines arthritis.by by review in clinical trials or awaiting and Drug Administration Food the U.S. (FDA). arthritisOf the 155 active clinical trials for have 97 States, in the United medicines startednot yet patients or recruiting to volunteers seek just begun to have Arthritis is part of related of a group of consisting diseases musculoskeletal that conditions than 100 different more in million people than 52 more affect the U.S. to according States, the United and Preven- Control Disease for Centers preva- The CDC projects tion (CDC). could diseases of musculoskeletal lence 2030 if current million by 67 to increase continue. trends Biopharmaceutical Research Companies Are Companies Research Biopharmaceutical One of the 100 for Nearly Medicines Developing in the Problems Health Chronic Most Common States United
5 Spondylitis 55
7 Rheumatoid Arthritis Rheumatoid
10
Psoriatic Arthritis Psoriatic 15 Osteoarthritis 3
Application Submitted Phase III Phase II Phase I
Musculoskeletal Pain Musculoskeletal
5 Gout Juvenile Arthritis Juvenile
A REPORT ON ARTHRITIS AND RELATED MUSCULOSKELETAL DISEASES MUSCULOSKELETAL AND RELATED ON ARTHRITIS A REPORT Arthritis MEDICINES IN DEVELOPMENT MEDICINES Medicines in Development in Development Medicines ArthritisFor Some medicines are listed in more than in more listed are Some medicines one category. Key Issues
MUSCULOSKELETAL Osteoarthritis is the most common joint disorder, resulting ARTHRITIS & DISEASES from aging and wear and tear on a joint. When the cartilage breaks down and wears away, the bones rub together, MORE AMERICANS causing pain, swelling, and stiffness. A medicine in develop- THAN AFFECTED BY 52 MILLION MORE THAN ment for osteoarthritis combines the function and specifi city of two monoclonal antibodies into one molecular entity in RHEUMATOID SPONDYLITIS ARTHRITIS order to target two different pro-infl ammatory cytokines— interleukin-1 alpha and interleukin-1 beta.
Psoriatic arthritis is a chronic autoimmune disease that oc- GOUT JUVENILE curs in a subset of individuals who have psoriasis and causes ARTHRITIS joint pain, stiffness and swelling. A medicine in development for psoriatic arthritis is a human monoclonal antibody that binds to the interleukin-17 (IL-17) receptor. When the medi- PSORIATIC ARTHRITIS OSTEOARTHRITIS cine attaches to the receptor, it prevents members of the IL-17 family from activating the receptor and exerting their DIFFERENT KINDS OF full effect on the body, leading to possible infl ammation. MUSCULOSKELETAL DISEASES 100 INCLUDING ARTHRITIS Rheumatoid arthritis is a progressive, systemic autoim- Source: U.S. Centers for Disease Control and Prevention (CDC). mune disease characterized by infl ammation and swelling of the membrane lining the joints, leading to destruction of the joint. A medicine in development for rheumatoid Researching and developing new medicines remains a risky arthritis inhibits two types of an enzyme (Janus kinase 1 investment and lengthy process. On average, it costs $1.2 and 2) that may play a role in rheumatoid arthritis. An- billion and between 10–15 years to bring a new medicine other medicine in development for rheumatoid arthritis is to patients. Despite that risk, America’s biopharmaceutical research companies continue to conduct the cutting-edge research needed to reduce the destructive toll of arthritis & MUSCULOSKELETAL and related musculoskeletal diseases. ARTHRITIS DISEASES
Medicines in the Pipeline 92 MEDICINES America’s biopharmaceutical research companies are explor- IN DEVELOPMENT ing many different approaches to treat musculoskeletal diseases. Among the 92 innovative medicines in development GOUT 5 for arthritis are potential treatments for: JUVENILE ARTHRITIS 3 Ankylosing spondylitis is a type of arthritis that most often MUSCULOSKELETAL PAIN 15 causes infl ammation in the bones and joints of the spine, but OSTEOARTHRITIS 10 can also affect other areas. Over time, the joints become swollen and infl amed, and can fuse together. One medicine PSORIATIC ARTHRITIS 7 in development for ankylosing spondylitis is a human mono- RHEUMATOID ARTHRITIS 55 clonal antibody that selectively binds to and neutralizes the SPONDYLITIS 5 pro-infl ammatory cytokine interleukin-17A, which causes infl ammation and affects bone biology. Researchers believe it Source: 2014 PhRMA Medicines in Development for Arthritis.s plays a role in several forms of arthritis.
2 Medicines in Development Arthritis 2014 Key Issues
a monoclonal antibody that targets the alpha receptor of granulocyte-macrophage colony stimulating factor (GM-CSF), a key factor in the infl ammatory process of rheumatoid arthritis.
MUSCULOSKELETAL MUSCULOSKELETAL ARTHRITIS & DISEASES ARTHRITIS & DISEASES EA CH YEAR BY 2030, THE NUMBER OF ARTHRITIS AND RELATED CONDITIONS PEOPLE DIAGNOSED WITH MUSCULOSKELETAL ACCOUNT FOR DISEASES COULD REACH 67 MILLION
AND NEARLY 44 MILLION 1 MILLION OUTPATIENT VISITS HOSPITALIZATIONS
Source: U.S. Centers for Disease Control and Prevention (CDC). Source: Arthritis Foundation.
ACCELERATING MEDICINES PARTNERSHIP PILOT PROGRAM SEEKS TO ADVANCE RESEARCH ON RHEUMATOID ARTHRITIS The Accelerating Medicines Partnership (AMP) is a groundbreaking partnership between the National Institutes of Health, several non-profi t disease foundations, 10 biopharmaceutical companies and PhRMA which began in 2014. The goal of the initiative is to transform the current model for developing new diagnostics and treatments by joining forces to identify and validate promising biological targets of disease. AMP represents a new, integrated approach to treatment discovery and seeks to increase the number of new diagnostics and therapies for patients while reducing the time and cost associated with their development. The initiative will begin with three pilot projects focused on the autoimmune diseases of rheumatoid arthritis and systemic lupus erythematosus, Alzheimer’s and type 2 diabetes. AMP data and analyses will be publicly accessible to the biomedical community.
Medicines in Development Arthritis 2014 3 Key Issues
Improving Quality of Life for MUSCULOSKELETAL & Rheumatoid Arthritis Patients ARTHRITIS DISEASES
Disease-modifying biological medicines have ushered in a new age of treatment for rheumatoid arthritis. By targeting Improved Quality of Life… the cells involved in the progression of rheumatoid arthritis, these medicines have dramatically slowed or even reversed the negative physical effects associated with the disease and made clinical remission possible for patients with severe disease. A 2010 study published in the Journal of Rheumatology found patients treated with combination therapy consisting of a new biologic and an older medicine had a 35 percent chance of complete clinical remission THEN NOW over the course of fi ve years, compared with 14 percent for those taking only the older medicine—more than doubling Treatments reduced joint DISEASE-MODIFYING inflammation but not ANTIRHEUMATIC DRUGS remission rates for patients. progression to disability target inflammation sources enabling disease remission
Source: C. Augustyn, B. Walker, and T.F. Goss. “Recognizing the Value of Innovation in the Treatment of Rheumatoid Arthritis.” Boston, MA: Healthcare Associates, March 2013.
Medicines in Development By Disease and Phase Some medicines are listed in more than one category.
All Medicines 92
Gout 5
Application Juvenile Arthritis 3 Submitted Phase III
Musculoskeletal Pain 15 Phase II Phase I
Osteoarthritis 10
Psoriatic Arthritis 7
Rheumatoid Arthritis 55
Spondylitis 5
4 Medicines in Development Arthritis 2014 Facts
Facts About Arthritis and Related Musculoskeletal Diseases
Overview Musculoskeletal Pain • Arthritis is part of a group of related musculoskeletal • Musculoskeletal diseases are a major cause of pain and diseases consisting of more than 100 different conditions reduced quality of life. Nearly 15 million adults report that affect people of all ages, races and genders.1 that they are unable to perform at least one common activity, such as self-care, walking, or rising from a chair, • Of the estimated 52.5 million Americans with some form on a regular basis due to their musculoskeletal condition.5 of arthritis, more than 4.6 million are African-Americans 2 and 2.9 million are Hispanic. Osteoarthritis • Arthritis is not just a disease of old age. About 40 • Osteoarthritis is a chronic condition and one of the percent of people with arthritis are under the age of 65, most common forms of arthritis, affecting approximately including approximately 294,000 children.2 27 million people in the United States. Common risk fac- tors include increasing age, obesity, previous joint injury, • Arthritis and related musculoskeletal diseases cost the overuse of the joint, weak thigh muscles, and genetics.2 U.S. economy nearly $128 billion per year in medical care and indirect expenses, including lost wages and • Nearly 50 percent of people by the age of 85 will de- productivity.2 velop symptomatic knee osteoarthritis.2
Gout Psoriatic Arthritis • Gout, a complex form of arthritis causing sudden, severe • The incidence of psoriatic arthritis in the United States attacks of pain, redness and tenderness in joints, occurs is estimated to be 6-7 people per 100,000 population more often in men than in women. Men also are more annually. The disease prevalence is approximately up to likely to develop gout earlier—usually between the ages 0.1 percent of the U.S. adult population. Peak incidence of 40 and 50—whereas women generally develop signs occurs between the ages of 30-55, and both sexes are and symptoms after menopause.3 equally affected.6
• A 2011 study shows the prevalence of gout in the United • Up to 30 percent of people with psoriasis also develop States has risen over the last twenty years and now psoriatic arthritis. In 85 percent of those people, psoria- affects 8.3 million Americans.4 sis on the skin preceded arthritis joint disease.7
Juvenile Arthritis Rheumatoid Arthritis • Juvenile arthritis refers to any form of arthritis or • About 1.5 million people in the United States have rheu- related condition that develops in children or teenagers matoid arthritis.2 Nearly three times as many women who are younger than age 18. Approximately 294,000 have the disease as men. In women, rheumatoid arthritis children are affected by juvenile arthritis and rheuma- most commonly begins between the ages of 30 and 60, tologic conditions, making it one of the most common whereas in men it often occurs later in life.1 childhood diseases in the United States.1
Medicines in Development Arthritis 2014 5 Facts
Spondylitis Sources: • Unlike other forms of arthritis and rheumatic diseases, 1. Arthritis Foundation, www.arthritis.org the general onset of ankylosing spondylitis commonly 2. U.S. Centers for Disease Control and Prevention, occurs in younger people between the ages of 17-45. www.cdc.gov However, it also can affect children and those who are 3. Mayo Clinic, www.mayoclinic.org much older. Ankylosing spondylitis is more common in men, but it occurs in women as well.8 4. American College of Rheumatology, www.rheumatology.org • About 2.7 million American adults are estimated to have 5. The Burden of Musculoskeletal Diseases, United States axial spondyloarthritis.2 Bone and Joint Initiative, www.boneandjointburden.org 6. Johns Hopkins Arthritis Center, www.hopkinsarthritis.org 7. National Psoriasis Foundation, www.psoriasis.org 8. Spondylitis Association of America, www.spondylitis.org
6 Medicines in Development Arthritis 2014 Medicines in Development for Arthritis
Gout
Product Name Sponsor Indication Development Phase*
arhalofenate CymaBay Therapeutics gout Phase II Newark, CA www.cymabay.com
febuxostat Takeda Pharmaceuticals gout Phase III extended release Deer eld, IL www.takeda.com
lesinurad AstraZeneca gout (chronic treatment) Phase III (selective uric acid reabsorption Wilmington, DE www.astrazeneca.com inhibitor)
RDEA3170 AstraZeneca chronic management of Phase II (selective uric acid Wilmington, DE hyperuricemia in patients www.astrazeneca.com reabsorption inhibitor) with gout
ulodesine BioCryst Pharmaceuticals gout Phase II completed (PNP inhibitor) Durham, NC www.biocryst.com
Juvenile Arthritis
Product Name Sponsor Indication Development Phase
Cimzia® UCB juvenile idiopathic arthritis Phase III certolizumab pegol Smyrna, GA (see also rheumatoid arthritis, www.ucb.com spondylitis)
Rasuvo™ Medac Pharma polyarticular-course juvenile application submitted methotrexate subcutaneous Chicago, IL rheumatoid arthritis www.medacpharma.com auto-injection (see also rheumatoid arthritis)
Simponi® Janssen Biotech juvenile idiopathic arthritis Phase III golimumab Horsham, PA www.janssenbiotech.com
*For more information about a specifi c medicine or company in the report, please use the website provided.
Medicines in Development Arthritis 2014 7 Medicines in Development for Arthritis
Musculoskeletal Pain While musculoskeletal pain is not a type of arthritis, it is included here as an important aspect of the disease.
Product Name Sponsor Indication Development Phase
AF-219 A erent Pharmaceuticals osteoarthritis pain Phase II (purinoceptor P2X3 antagonist) San Mateo, CA www.afferentpharma.com
BEMA™ Endo Pharmaceuticals osteoarthritis pain Phase III buprenorphine transmucosal Malvern, PA www.endo.com
Botox® Allergan osteoarthritis pain Phase II onabotulinum toxin A Irvine, CA www.allergan.com
cebranopadol Actavis osteoarthritis pain of the knee Phase II completed (GRT6005) New York, NY www.actavis.com Grünenthal Aachen, Germany
EP4-R antagonist Eli Lilly osteoarthritis pain Phase I Indianapolis, IN www.lilly.com
FX005 Flexion Therapeutics end-stage osteoarthritis pain Phase II completed (sustained release p38 inhibitor) Burlington, MA www.flexiontherapeutics.com
FX006 Flexion Therapeutics moderate to severe osteoarthritis pain Phase II (sustained release steroid) Burlington, MA www.flexiontherapeutics.com
NKTR-181 Nektar Therapeutics osteoarthritis pain of the knee Phase II completed (mu-opioid analgesic) San Francisco, CA www.nektar.com
OLT1177 gel Olatec Industries moderate to severe osteoarthritis pain Phase II Rye Brook, NY of the knee
SoluMatrix® Meloxicam Iroko Pharmaceuticals osteoarthritis pain Phase III nanoparticle paroduct Philadelphia, PA www.iroko.com
SoluMatrix® Naproxen Iroko Pharmaceuticals osteoarthritis pain Phase II nanoparticle paroduct Philadelphia, PA www.iroko.com
SYNVISC-ONE® Sano US osteoarthritis pain of the hip Phase III Bridgewater, NJ www.sano .com
TV-45070 Teva Pharmaceutical osteoarthritis pain Phase II (sodium channel inhibitor) Petach Tikvah, Israel www.tevapharm.com Xenon Pharmaceuticals www.xenon-pharma.com Burnaby, Canada
V116517 Purdue Pharma osteoarthritis pain of the knee Phase II completed Stamford, CT www.purduepharma.com
8 Medicines in Development Arthritis 2014 Medicines in Development for Arthritis
Musculoskeletal Pain
Product Name Sponsor Indication Development Phase
Zorvolex™ Iroko Pharmaceuticals osteoarthritis pain application submitted diclofenac Philadelphia, PA www.iroko.com
Osteoarthritis
Product Name Sponsor Indication Development Phase
ABT-981 AbbVie osteoarthritis of the knee Phase II (IL-1 alpha/IL-1 beta inhibitor) North Chicago, IL www.abbvie.com
Ampion™ Ampio Pharmaceuticals osteoarthritis of the knee Phase III Greenwood Village, CO www.ampiopharma.com
BI 1026706 Boehringer Ingelheim Pharmaceuticals osteoarthritis Phase I Ridge eld, CT www.boehringer-ingelheim.com
Cartistem® Medipost osteoarthritis Phase I/II mesenchymal stem cell therapy for Seoul, South Korea www.medi-post.com cartilage repair
gevokizumab XOMA erosive osteoarthritis of the hand Phase II Berkeley, CA www.xoma.com
ibuprofenamine Tech elds Pharma osteoarthritis of the knee Phase II (X0002) Jiangsu, China www.tfpharma.com
SM-04690 Samumed osteoarthritis of the knee Phase I (Wnt signaling pathway San Diego, CA www.samumed.com modulator)
sprifermin EMD Serono osteoarthritis Phase II (FGF-18) Rockland, MA www.emdserono.com
TG-C TissueGene osteoarthritis of the knee Phase II (cell therapy) Rockville, MD www.tissuegene.com
TPX-100 OrthoTrophix osteoarthritis of the knee Phase II (MEPE-derived 23-amino acid Oakland, CA www.orthotrophix.com peptide)
Medicines in Development Arthritis 2014 9 Medicines in Development for Arthritis
Psoriatic Arthritis
Product Name Sponsor Indication Development Phase
brodalumab Amgen psoriatic arthritis Phase III (anti-IL-17R mAb) Thousand Oaks, CA www.amgen.com AstraZeneca www.astrazeneca.com Wilmington, DE
clazakizumab Bristol-Myers Squibb psoriatic arthritis Phase II (BMS-945429) Princeton, NJ (see also rheumatoid arthritis) www.bms.com
ixekizumab Eli Lilly psoriatic arthritis Phase III (IL-17 inhibitor) Indianapolis, IN www.lilly.com
Orencia® Bristol-Myers Squibb psoriatic arthritis Phase III abatacept Princeton, NJ www.bms.com (subcutaneous)
secukinumab Novartis Pharmaceuticals psoriatic arthritis application submitted (IL-17 inhibitor) East Hanover, NJ (see also rheumatoid arthritis, www.novartis.com spondylitis)
ShK-186 Kineta psoriatic arthritis Phase I (Kv1.3 potassium channel blocker) Seattle, WA www.kinetabio.com
Xeljanz® P zer psoriatic arthritis Phase III tofacitinib New York, NY (see also spondylitis) www.p zer.com
Rheumatoid Arthritis
Product Name Sponsor Indication Development Phase
ABP 501 Amgen rheumatoid arthritis Phase III (adalimumab biosimilar) Thousand Oaks, CA www.amgen.com
ABT-122 AbbVie rheumatoid arthritis Phase I (IL-17/TNF inhibitor) North Chicago, IL www.abbvie.com
ABT-494 AbbVie rheumatoid arthritis Phase II (JAK1/JAK2/JAK3 inhibitor) North Chicago, IL www.abbvie.com
allogeneic mesenchymal Mesoblast rheumatoid arthritis Phase II precursor cells New York, NY www.mesoblast.com
10 Medicines in Development Arthritis 2014 Medicines in Development for Arthritis
Rheumatoid Arthritis
Product Name Sponsor Indication Development Phase
ALX-0061 AbbVie rheumatoid arthritis Phase I/II (IL-6 receptor modulator) North Chicago, IL www.abbvie.com Ablynx www.ablynx.com Ghent, Belgium
ASP015K Astellas Pharma rheumatoid arthritis Phase II (JAK3 inhibitor) Tokyo, Japan www.astellas.com Janssen Research & Development www.janssenrnd.com Raritan, NJ
baricitinib Eli Lilly rheumatoid arthritis Phase III (JAK1/JAK2 inhibitor) Indianapolis, IN www.lilly.com Incyte www.incyte.com Wilmington, DE
BI 655064 Boehringer Ingelheim Pharmaceuticals rheumatoid arthritis Phase I (CD40 antigen inhibitor) Ridge eld, CT www.boehringer-ingelheim.com
BI 695500 Boehringer Ingelheim Pharmaceuticals rheumatoid arthritis Phase III (rituximab biosimilar) Ridge eld, CT www.boehringer-ingelheim.com
BI 695501 Boehringer Ingelheim Pharmaceuticals rheumatoid arthritis Phase I (adalimumab biosimilar) Ridge eld, CT www.boehringer-ingelheim.com
BT-016 AbbVie rheumatoid arthritis Phase II (tregalizumab) North Chicago, IL www.abbvie.com
Btk inhibitor Pharmacyclics rheumatoid arthritis Phase I Sunnyvale, CA www.pharmacyclics.com
Cadherin-11 Adheron Therapeutics rheumatoid arthritis Phase I completed (SDP051) Berkeley, CA www.adherontherapeutics.com
CC-292 Celgene rheumatoid arthritis Phase II (Btk inhibitor) Summit, NJ www.celgene.com
CCX354 ChemoCentryx rheumatoid arthritis Phase I (CCR1 chemokine receptor) Mountain View, CA www.chemocentryx.com
CF101 Can-Fite BioPharma rheumatoid arthritis Phase II (adenosine A3 receptor agonist) Waltham, MA www.canfite.com
CFZ533 Novartis Pharmaceuticals rheumatoid arthritis Phase I East Hanover, NJ www.novartis.com
CHS-0214 Coherus Biosciences rheumatoid arthritis Phase III (etanercept biosimilar) Redwood City, CA www.coherus.com
Medicines in Development Arthritis 2014 11 Medicines in Development for Arthritis
Rheumatoid Arthritis
Product Name Sponsor Indication Development Phase
Cimzia® UCB early active rheumatoid arthritis Phase III certolizumab pegol Smyrna, GA (see also juvenile arthritis, www.ucb.com spondylitis)
clazakizumab Bristol-Myers Squibb rheumatoid arthritis Phase II (BMS-945429) Princeton, NJ (see also psoriatic arthritis) www.bms.com
CNTO 6785 Janssen Research & Development rheumatoid arthritis Phase II (IL-17A modulator) Raritan, NJ www.janssenrnd.com
Dekavil P zer rheumatoid arthritis Phase I F8 antibody-IL-IO New York, NY www.p zer.com
FPA008 Five Prime Therapeutics rheumatoid arthritis Phase I (IL-34/CSF1 inhibitor) South San Francisco, CA www. veprime.com
GLPG0634 AbbVie rheumatoid arthritis Phase II (JAK1 inhibitor) North Chicago, IL www.abbvie.com Galapagos www.glpg.com Mechelen, Belgium
GSK3117391 GlaxoSmithKline rheumatoid arthritis Phase I (macrophage targeted Research Triangle Park, NC www.gsk.com histone deacetylase inhibitor)
GSK3196165 GlaxoSmithKline rheumatoid arthritis Phase II (MOR103) Research Triangle Park, NC www.gsk.com (granulocyte macrophage colony-stimulating factor mAb)
guselkumab Janssen Research & Development rheumatoid arthritis Phase II completed (CNTO 1959) Raritan, NJ www.janssenrnd.com
INCB47986 Incyte rheumatoid arthritis Phase I (JAK1 inhibitor) Wilmington, DE www.incyte.com
IPI-145 In nity Pharmaceuticals rheumatoid arthritis Phase II (dual PI3K inhibitor) Cambridge, MA www.in .com
JNJ-38518168 Janssen Research & Development rheumatoid arthritis Phase II (histamine H4 receptor antagonist) Raritan, NJ www.janssenrnd.com
JNJ-40346527 Janssen Research & Development rheumatoid arthritis Phase II completed (FMS inhibitor) Raritan, NJ www.janssenrnd.com
KD025 Kadmon rheumatoid arthritis Phase I (ROCK2 inhibitor) New York, NY www.kadmon.com
12 Medicines in Development Arthritis 2014 Medicines in Development for Arthritis
Rheumatoid Arthritis
Product Name Sponsor Indication Development Phase
(L/D)-aminopterin Syntrix Biosystems rheumatoid arthritis Phase II Auburn, WA www.syntrixbio.com
LY3090106 Eli Lilly rheumatoid arthritis Phase I Indianapolis, IN www.lilly.com
mavrilimumab MedImmune rheumatoid arthritis Phase II (anti-GM-CSFR mAb) Gaithersburg, MD www.medimmune.com
MK-8808 Merck rheumatoid arthritis Phase I (rituximab biosimilar) Whitehouse Station, NJ www.merck.com
MORAb-022 Eisai rheumatoid arthritis Phase I (IgG1 mAb) Woodcli Lake, NJ www.eisai.com
NN8210 Novo Nordisk rheumatoid arthritis Phase I (anti-C5aR-215) Plainsboro, NJ www.novonordisk.com
NN8226 Novo Nordisk rheumatoid arthritis Phase II (anti-IL20 antibody) Plainsboro, NJ www.novonordisk.com
Otezla® Celgene rheumatoid arthritis Phase II apremilast Summit, NJ (see also spondylitis) www.celgene.com
PF-04171327 P zer rheumatoid arthritis Phase II (selective glucocorticoid receptor New York, NY www.p zer.com modulator)
PF-05280586 P zer rheumatoid arthritis Phase I (rituximab biosimilar) New York, NY www.p zer.com
PF-06410293 P zer rheumatoid arthritis Phase I (adalimumab biosimilar) New York, NY www.pfizer.com
PF-06438179 P zer rheumatoid arthritis Phase I (in iximab biosimilar) New York, NY www.p zer.com
PRTX-100 Protalex active rheumatoid arthritis Phase I (staphylococcal protein A) Florham Park, NJ www.protalex.com
QAL964 Novartis Pharmaceuticals rheumatoid arthritis Phase II East Hanover, NJ www.novartis.com
Medicines in Development Arthritis 2014 13 Medicines in Development for Arthritis
Rheumatoid Arthritis
Product Name Sponsor Indication Development Phase
Rasuvo™ Medac Pharma rheumatoid arthritis application submitted methotrexate subcutaneous Chicago, IL (see also juvenile arthritis) www.medacpharma.com auto-injection pen
Ravax™ Immune Response BioPharma rheumatoid arthritis Phase III rheumatoid arthritis vaccine Atlantic City, NJ www.immuneresponsebiopharma. com
SAN-300 Salix Pharmaceuticals rheumatoid arthritis Phase II (VLA-1 mAb) Raleigh, NC www.salix.com
sarilumab Regeneron Pharmaceuticals rheumatoid arthritis Phase III (anti-IL-6R mAb) Tarrytown, NY www.regeneron.com Sano US www.sano .com Bridgewater, NJ
secukinumab Novartis Pharmaceuticals rheumatoid arthritis Phase III (IL-17 inhibitor) East Hanover, NJ (see also psoriatic arthritis, www.novartis.com spondylitis)
sirukumab Janssen Research & Development rheumatoid arthritis Phase III (IL-6 mAb) Raritan, NJ www.janssenrnd.com
Stelara® Janssen Research & Development rheumatoid arthritis Phase II completed ustekinumab Raritan, NJ www.janssenrnd.com
VX-509 Vertex Pharmaceuticals rheumatoid arthritis Phase II (JAK3 inhibitor) Boston, MA www.vrtx.com
XmAb® 5871 Xencor moderate to severe rheumatoid Phase II anti-CD19 mAb Monrovia, CA arthritis www.xencor.com
Spondylitis
Product Name Sponsor Indication Development Phase
BI 655066 Boehringer Ingelheim Pharmaceuticals ankylosing spondylitis Phase II (IL-23 subunit p19 inhibitor) Ridge eld, CT www.boehringer-ingelheim.com
Cimzia® UCB axial spondyloarthritis application submitted certolizumab pegol Smyrna, GA (see also juvenile arthritis, www.ucb.com rheumatoid arthritis)
14 Medicines in Development Arthritis 2014 Medicines in Development for Arthritis
Spondylitis
Product Name Sponsor Indication Development Phase
Otezla® Celgene ankylosing spondylitis Phase III apremilast Summit, NJ (see also rheumatoid arthritis) www.celgene.com
secukinumab Novartis Pharmaceuticals ankylosing spondylitis Phase III (IL-17 inhibitor) East Hanover, NJ (see also psoriatic arthritis, www.novartis.com rheumatoid arthritis)
Xeljanz® P zer ankylosing spondylitis Phase II tofacitinib New York, NY (see also psoriatic arthritis) www.p zer.com
Defi nitions Application submitted—An application for marketing has been submitted to the U.S. Food and Drug Administration (FDA). The application can either be an NDA (new drug application) or a BLA (biologic license application).
Phase I—Researchers test the drug in a small group of people, usually between 20 and 100 healthy adult volunteers, to evaluate its initial safety and tolerability profile, determine a safe dosage range, and identify potential side effects.
Phase II—The drug is given to volunteer patients, usually between 100 and 500, to determine whether the drug is effective, identify an optimal dose, and to evaluate further its short-term safety.
Phase III—The drug is given to a larger, more diverse patient population, often involving between 1,000 and 5,000 patients (but sometimes many more thousands), to generate statistically significant evidence to confirm its safety and effectiveness. Phase III studies are the longest studies and usually take place in multiple sites around the world.
The content of this report has been obtained through public, government and industry sources, and the Adis “R&D Insight” database based on the latest information. Report current as of July 14, 2014. The medicines in this report include medi- cines being developed by U.S.-based companies conducting trials in the United States and abroad, PhRMA-member compa- nies conducting trials in the United States and abroad, and foreign companies conducting clinical trials in the United States. The information in this report may not be comprehensive. For more specifi c information about a particular product, contact the individual company directly or go to www.clinicaltrials.gov. The entire series of Medicines in Development is available on PhRMA’s website. A publication of PhRMA’s Communications & Public Affairs Department (202) 835-3460 www.phrma.org | www.innovation.org | www.pparx.org Provided as a public service by PhRMA. Founded in 1958 as the Pharmaceutical Manufacturers Association. Copyright © 2014 by the Pharmaceutical Research and Manufacturers of America. Permission to reprint is awarded if proper credit is given.
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Medicines in Development Arthritis 2014 15 The Drug Discovery, Development and Approval Process
Developing a new medicine takes an average of 10-15 years. Of the tens of thousands of compounds screened, only one is approved.
The Drug Development and Approval Process The U.S. system of new drug approvals is per- pany fi les an IND with the U.S. Food and Drug (but sometime many more thousands), to gener- haps the most rigorous in the world. Administration (FDA) to begin to test the drug ate statistically signifi cant evidence to confi rm It takes 10-15 years, on average, for an experi- in people. The IND shows results of previous its safety and effectiveness. They are the lon- mental drug to travel from lab to U.S. patients, experiments; how, where and by whom the new gest studies, and usually take place in multiple according to the Tufts Center for the Study of studies will be conducted; the chemical structure sites around the world. Drug Development. Tens of thousands of com- of the compound; how it is thought to work in New Drug Application (NDA)/Biologic License pounds may be screened early in development, the body; any toxic effects found in the animal Application (BLA). Following the completion but only one ultimately receives approval. Even studies; and how the compound is manufac- of all three phases of clinical trials, a company medicines that reach clinical trials have only a tured. All clinical trials must be reviewed and ap- analyzes all of the data and fi les an NDA or BLA 16 percent chance of being approved. proved by the Institutional Review Board (IRB) with FDA if the data successfully demonstrate where the trials will be conducted. Progress On average, it costs a company $1.2 billion, both safety and effectiveness. The applications reports on clinical trials must be submitted at including the cost of failures, to get one new contain all of the scientifi c information that the least annually to FDA and the IRB. medicine from the laboratory to U.S. patients, company has gathered. Applications typically according to a 2007 study by the Tufts Center Clinical Trials, Phase I—Researchers test the run 100,000 pages or more. for the Study of Drug Development. More recent drug in a small group of people, usually between Approval. Once FDA approves an NDA or BLA, studies estimate the cost to be even higher. 20 and 100 healthy adult volunteers, to evaluate the new medicine becomes available for physi- its initial safety and tolerability profi le, deter- Once a new compound has been identifi ed in cians to prescribe. A company must continue mine a safe dosage range, and identify potential the laboratory, medicines are usually developed to submit periodic reports to FDA, including side effects. as follows: any cases of adverse reactions and appropriate Clinical Trials, Phase II—The drug is given quality-control records. For some medicines, Preclinical Testing. A pharmaceutical company to volunteer patients, usually between 100 and FDA requires additional trials (Phase IV) to conducts laboratory and animal studies to show 500, to see if it is effective, identify an optimal evaluate long-term effects. biological activity of the compound against the dose, and to further evaluate its short-term targeted disease, and the compound is evalu- Discovering and developing safe and effective safety. ated for safety. new medicines is a long, diffi cult, and expensive Clinical Trials, Phase III—The drug is given to a process. PhRMA member companies invested an Investigational New Drug Application (IND). larger, more diverse patient population, often estimated $51.1 billion in research and develop- After completing preclinical testing, a com- involving between 1,000 and 5,000 patients ment in 2013.