2011 REPO

Medicines in Development PARKINSON’S DISEASE R

presented by america’s biopharmaceutical T research companies

More Than 30 Medicines Are Being Developed to Treat Parkinson’s Disease and Related Conditions

Medicines in Development for Parkinson’s Disease* An estimated 1 million 26 Americans suffer from the disease, with 60,000 newly diagnosed each year

America’s biopharmaceutical research compa- ‡1HZGHOLYHU\PHFKDQLVPVRIFXUUHQWO\ nies are currently developing 36 medicines to approved treatments, including a help the nearly 1 million Americans suffering transdermal patch and an intranasal from Parkinson’s disease, a motor system formulation. disorder resulting from the loss of - 13 ‡0HGLFLQHVWRWUHDWDPRWRUIXQFWLRQ producing brain cells. All of the medicines are disorder associated with Parkinson’s either in clinical trials or awaiting review by the disease treatment. U.S. Food and Drug Administration. Researching and developing new medicines Each year, approximately 60,000 Americans remains a risky investment and lengthy are diagnosed with Parkinson’s disease, and process—costing, on average, $1.2 billion, incidence increases with age. The combined including the cost of failures, and taking cost to the U.S. economy in direct and indirect between 10–15 years to bring a new medicine expenses is nearly $25 billion a year, accord- to patients. But advances in our understand- 2 ing to the Parkinson’s Disease Foundation. ing of diseases and how to treat them have The medicines today in the research and allowed America’s biopharmaceutical research e development pipeline offer hope of reducing companies to conduct the cutting-edge the human and economic costs of Parkinson’s research needed to reduce the destructive toll of Parkinson’s disease and to allow more s Diseas disease. They include: Diagnosis patients to lead healthier, happier, more ‡*HQHWKHUDSLHVWKDWWDUJHWVSHFL¿FDUHDV productive lives. Related Conditions Parkinson’ in the brain. ‡&HOOWKHUDS\WKDWXVHVDSDWLHQW¶VRZQ * Some medicines are listed in cells to reverse effects of the disease. more than one category. Medicines in Development for Parkinson’s Disease

PARKINSON’S DISEASE

Product Name Sponsor Indication Development Status*

AAD-2004 Amkor Pharma Parkinson’s disease Phase I Sammamish, WA www.neurotech-pharma.com 1HXURWHFK3KDUPDFHXWLFDOV Seoul, South Korea

$$9$$'& *HQ]\PH Parkinson’s disease Phase I (gene therapy) Cambridge, MA (617) 252-7500

Altea Therapeutics Parkinson’s disease Phase I transdermal patch Atlanta, GA (404) 835-6310

autologous stem cell therapy 1HXUR*HQHUDWLRQ Parkinson’s disease Phase I Los Angeles, CA (310) 659-3880

AZD3241 AstraZeneca Parkinson’s disease Phase I Wilmington, DE (800) 236-9933

&(5( &HUHJHQH Parkinson’s disease Phase II $$9171 San Diego, CA (858) 458-8800

'0 Depomed Parkinson’s disease Phase I completed (levodopa/carbidopa Menlo Park, CA (650) 462-5900 controlled-release)

droxidopa &KHOVHD7KHUDSHXWLFV WUHDWPHQWRIIUHH]LQJRIJDLWLQ Phase I/II Charlotte, NC Parkinson’s disease patients (704) 341-1516 (see also related conditions)

Duodopa® Abbott Laboratories late-stage Parkinson’s disease Phase III levodopa/carbidopa Abbott Park, IL (Fast Track) (847) 937-6100 intraduodenal gel (Orphan Drug)

¿SDPH]ROH Santhera Pharmaceuticals Parkinson’s disease Phase II completed Charlestown, MA (Fast Track) (617) 886-5161

HT-1067 Helicon Therapeutics Parkinson’s disease Phase I San Diego, CA (858) 246-8120

IPX066 ,03$;3KDUPDFHXWLFDOV early-stage Parkinson’s disease Phase III (levodopa/carbidopa Hayward, CA (510) 240-6000 extended-release capsules) ------late-stage Parkinson’s disease Phase III (510) 240-6000

)RUPRUHLQIRUPDWLRQDERXWDVSHFL¿FPHGLFLQHLQWKLVUHSRUWSOHDVHFDOOWKHWHOHSKRQHQXPEHUOLVWHG

2 Medicines in Development Parkinson’s Disease 2011 Medicines in Development for Parkinson’s Disease

PARKINSON’S DISEASE

Product Name Sponsor Indication Development Status

istradefylline Kyowa Hakko Kirin Pharma Parkinson’s disease application submitted (KW-6002) Princeton, NJ (adjunctive treatment) (609) 919-1100

Neupro® 8&% late-stage Parkinson’s disease application submitted transdermal Smyrna, GA (770) 970-7500

nitisinone Biotie Therapies Parkinson’s disease Phase II 6<1 South San Francisco, CA (650) 244-4850

1/;3 1HXURORJL[ Parkinson’s disease Phase II *$'JHQHWKHUDS\ Fort Lee, NJ (Fast Track) (866) 604-8665

OS-320 Osmotica Pharmaceutical Parkinson’s disease Phase II completed Wilmington, NC (910) 509-0114

Parkinson’s disease %LR0HGLFD Parkinson’s disease Phase I/II gene therapy San Diego, CA (858) 677-6500 2[IRUG%LR0HGLFD Oxford, United Kingdom

Parkinson’s disease 6WHPHGLFD&HOO7HFKQRORJLHV Parkinson’s disease in clinical trials stem cell therapy San Diego, CA (858) 658-0910

preladenant 0HUFN early-stage Parkinson’s disease Phase III 6&+ Whitehouse Station, NJ (Fast Track) (800) 672-6372 (see also related conditions) ------late-stage and mid-stage Phase III Parkinson’s disease (800) 672-6372 (Fast Track)

3<0 Phytopharm Parkinson’s disease Phase II Huntingdon, United Kingdom www.phytopharm.com

VD¿QDPLGH (0'6HURQR early-stage Parkinson’s disease Phase III Rockland, MA (see also related conditions) (800) 283-8088 ------late-stage and mid-stage Phase III Parkinson’s disease (800) 672-6372

631 Supernus Pharmaceuticals Parkinson’s disease Phase I Rockville, MD (301) 838-2500

WR]DGHQDQW Biotie Therapies Parkinson’s disease Phase II 6<1 South San Francisco, CA (650) 244-4850

Medicines in Development Parkinson’s Disease 2011 3 Medicines in Development for Parkinson’s Disease

PARKINSON’S DISEASE

Product Name Sponsor Indication Development Status

V1512 Vernalis Parkinson’s disease Phase II Winnersh, United Kingdom www.vernalis.com

XP21279 XenoPort Parkinson’s disease Phase II Santa Clara, CA (408) 616-7200

PARKINSON’S DISEASE — DIAGNOSIS

Product Name Sponsor Indication Development Status

Altropane® Alseres Pharmaceuticals Parkinson’s disease Phase III molecular imaging agent Hopkinton, MA (diagnosis) (508) 497-2360

ÀRUEHWDSLU)LQMHFWLRQ Avid Radiopharmaceuticals Parkinson’s disease Phase II Philadelphia, PA (diagnosis) (215) 298-0700

PARKINSON’S DISEASE — RELATED CONDITIONS

Product Name Sponsor Indication Development Status

ADS-5102 Adamas Pharmaceuticals levodopa-induced dyskinesia Phase II/III (amantadine controlled-release) Emeryville, CA (510) 450-3500

AFQ056 1RYDUWLV3KDUPDFHXWLFDOV levodopa-induced dyskinesia Phase II East Hanover, NJ (888) 669-6682

AQW051 1RYDUWLV3KDUPDFHXWLFDOV levodopa-induced dyskinesia Phase II East Hanover, NJ (888) 669-6682

dipraglurant-IR Addex Pharmaceuticals levodopa-induced dyskinesia Phase II (ADX48621) Geneva, Switzerland www.addexpharma.com

droxidopa &KHOVHD7KHUDSHXWLFV neurogenic orthostatic hypotension Phase III (Orphan Drug) Charlotte, NC associated with Parkinson’s disease (704) 341-1516 (Fast Track) (see also Parkinson’s disease)

QDOX]RWDQ Proximagen levodopa-induced dyskinesia Phase I London, United Kingdom www.proximagen.com

4 Medicines in Development Parkinson’s Disease 2011 Medicines in Development for Parkinson’s Disease

PARKINSON’S DISEASE — RELATED CONDITIONS

Product Name Sponsor Indication Development Status

1+ 1HXUR+HDOLQJ3KDUPDFHXWLFDOV sialorrhea associated with Phase II Waban, MA Parkinson’s disease (617) 331-4111

13 1HXUDOWXV3KDUPDFHXWLFDOV levodopa-induced dyskinesia Phase I/II Palo Alto, CA (650) 424-1600

OP-014 Orient Pharma sialorrhea associated with Phase II (clonidine/oxybutynin) Taipei, Taiwan Parkinson’s disease www.oep.com.tw

SLFOR]RWDQ Asubio Pharmaceuticals dyskinesia associated with Phase II completed Paramus, NJ Parkinson’s disease (201) 368-5020

$&$',$3KDUPDFHXWLFDOV Parkinson’s disease-associated Phase III $&3 San Diego, CA psychosis (858) 558-2871

preladenant 0HUFN levodopa-induced dyskinesia Phase I 6&+ Whitehouse Station, NJ (see also Parkinson’s disease) (800) 672-6372

VD¿QDPLGH (0'6HURQR cognitive impairment associated Phase II Rockland, MA with Parkinson’s disease (800) 283-8088 (see also Parkinson’s disease) ------levodopa-induced dyskinesia Phase II (800) 283-8088

Medicines in Development Parkinson’s Disease 2011 5 Glossary

application submitted—An application for The frequency of communication assures that chewing, and speaking; urinary problems or marketing has been submitted by the company questions and issues are resolved quickly, constipation; skin problems; and sleep disrup- to the Food and Drug Administration (FDA). often leading to earlier drug approval and tions. Although some people become se- access by patients. verely disabled, others experience only minor dyskinesia—An impairment in the ability PRWRUGLVUXSWLRQV1RRQHFDQSUHGLFWZKLFK WRFRQWUROPRYHPHQWVFKDUDFWHUL]HGE\ neurogenic orthostatic hypotention—A drop symptoms will affect an individual patient, and spasmodic or repetitive motions or lack of in blood pressure when changing position from the intensity of the symptoms also varies from coordination. Levodopa is a drug that effec- lying to sitting or from sitting to standing, which person to person. tively eliminates the major motor symptoms of FDXVHVOLJKWKHDGHGQHVVRUGL]]LQHVV,WLVD PD and helps a person move again; however, common symptom of Parkinson’s disease and Phase 0—First-in-human trials conducted levodopa sometimes creates dyskinesia by can make patients pass out and fall. in accordance with FDA’s 2006 guidance on causing too much movement. H[SORUDWRU\,QYHVWLJDWLRQDO1HZ'UXJ ,1'  Parkinson’s disease (PD)—PD belongs to studies designed to speed up development of Fast Track—A process designed to facilitate a group of conditions called motor system promising drugs by establishing very early on the development and expedite the review disorders, which are the result of the loss of whether the agent behaves in human subjects RIGUXJVWRWUHDWVHULRXVGLVHDVHVDQG¿OODQ dopamine-producing brain cells. The four pri- as was anticipated from preclinical studies. unmet medical need. The status is assigned mary symptoms of PD are tremor, or trembling by the U.S. Food and Drug Administration. in hands, arms, legs, jaw, and face; rigidity, or Phase I—Safety testing and pharmacological The purpose is to get important new drugs stiffness of the limbs and trunk; bradykinesia, SUR¿OLQJLQKXPDQV to the patient earlier. Fast Track addresses a or slowness of movement; and postural insta- EURDGUDQJHRIVHULRXVGLVHDVHV*HQHUDOO\ bility, or impaired balance and coordination. Phase II—Effectiveness and safety testing in determining factors include whether the drug PD is both chronic, meaning it persists over a humans. will have an impact on such factors as survival, long period of time, and progressive, meaning Phase III—Extensive clinical trials to demon- day-to-day functioning, or the likelihood that its symptoms grow worse over time. As these VWUDWHVDIHW\DQGHI¿FDF\LQKXPDQV the disease, if left untreated, will progress symptoms become more pronounced, patients from a less severe condition to a more serious PD\KDYHGLI¿FXOW\ZDONLQJWDONLQJRUFRPSOHW- sialorrhea—Drooling or excessive salivation, RQH)LOOLQJDQXQPHWPHGLFDOQHHGLVGH¿QHG ing other simple tasks. Early symptoms of PD which is a common problem in neurologically as providing a therapy where none exists or are subtle and occur gradually. In some people, impaired children (e.g., those with mental providing a therapy which may be potentially the disease progresses more quickly than in retardation or cerebral palsy) and in adults who superior to existing therapy. Once a drug others. As the disease progresses, the tremor, have Parkinson’s disease or have had a . receives Fast Track designation, early and which affects the majority of PD patients, may It is commonly most caused by poor oral and frequent communication between the FDA and begin to interfere with daily activities. Other facial muscle control. a drug company is encouraged throughout the symptoms may include depression and other entire drug development and review process. HPRWLRQDOFKDQJHVGLI¿FXOW\LQVZDOORZLQJ

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 October 24, 2011.7KHLQIRUPDWLRQLQWKLVUHSRUWPD\QRWEHFRPSUHKHQVLYH)RUPRUHVSHFL¿FLQIRUPDWLRQ about a particular product, contact the individual company directly or go to www.clinicaltrials.gov. The entire series of 0HGLFLQHVLQ'HYHORSPHQW is available on PhRMA’s web site. A publication of PhRMA’s Communications & Public Affairs Department. (202) 835-3460 www.phrma.org | www.innovation.org | www.pparx.org | www.buysafedrugs.info 3URYLGHGDVD3XEOLF6HUYLFHE\3K50$)RXQGHGLQDVWKH3KDUPDFHXWLFDO0DQXIDFWXUHUV$VVRFLDWLRQ

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6 Medicines in Development Parkinson’s Disease 2011 Selected Facts about Parkinson’s Disease in the United States

Overview

‡ The number of people in the United States ‡ Parkinson’s disease affects both men productivity a major factor in the societal 2 with Parkinson’s disease is estimated to and women. The average age of onset of impact of the disease. be as many as 1 million, more than all Parkinson’s disease is 61, but it may begin ‡ Parkinson’s disease reduces life expec- people diagnosed with multiple sclerosis, as early as age 40 or even before.2 tancy by an average of three to nine years muscular dystrophy and amyotrophic ‡ People as young as 18 have been diag- and is now the 14th leading cause of death lateral sclerosis combined. Approximately 2 nosed with Parkinson’s disease.3 in the United States. 60,000 Americans are newly diagnosed 1 each year. ‡ Forty percent of people affected by Par- ‡ Red haired people have double the risk kinson’s disease are under the age of 60, of developing Parkinson’s Disease. The ‡ As the American population ages, those placing them squarely in the workforce. Ex- pigment that colors hair red is made from numbers are expected to grow. Worldwide, perts say that about one-third of employed L-dopa, just as is dopamine, the substance the number of people with Parkinson’s individuals will lose their jobs within a year ZKRVHGH¿FLHQF\FDXVHV3DUNLQVRQ¶V disease is expected to double in the next 4 of a Parkinson’s diagnosis, making lost disease. 25 years.2

Economic Impact

‡ According to the Parkinson’s Action people in early stages of the disease, and or nursing home may be required, and the 1HWZRUNGUXJVFRPPRQO\XVHGWRWUHDW it is probably much higher for advanced costs can exceed $100,000 per person 2 2 Parkinson’s disease cost between $1,000 stages. annually. and $6,000 each year per patient.2 ‡ Surgical treatments for Parkinson’s dis- ‡ In the United States, the combined direct 2 ‡ Annual medical care, including doctors’ ease can cost $25,000 or more. and indirect cost of Parkinson’s disease is visits, physical therapies, and treatment for estimated to be $25 billion per year. This ‡ As Parkinson’s disease progresses, insti- co-occurring illnesses (such as depres- includes treatment costs, Social Security tutional care at an assisted-living facility 1 sion), is estimated at $2,000 to $7,000 for payments, and lost productivity.

Sources:

1. Parkinson’s Disease Foundation (www.pdf.org)

 7KH0LFKDHO6WHUQ3DUNLQVRQ¶V5HVHDUFK)RXQGDWLRQ (www.parkinsoninfo.org)

 3DUNLQVRQ¶V$FWLRQ1HWZRUN(www.parkinsonsaction.org)

4. Viartis (www.viartis.net)

Medicines in Development Parkinson’s Disease 2011 7 The Drug Discovery, Development and Approval Process

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Clinical Trials

Discovery/ Preclinical Testing Phase I Phase II Phase III FDA Phase IV

Years 6.5 1.5 2 3.5 1.5 FDA

20 to 100 100 to 500 1,000 to 5,000 Test Laboratory and at FDA

healthy patient patient Population animal studies

at Additional

volunteers volunteers volunteers Review post- process/ marketing Confirm Assess safety, Evaluate approval testing

File IND Determine effectiveness, biological activity effective- required Purpose safety monitor adverse and formulations ness, look for File NDA/BLA by FDA and dosage reactions from side effects long-term use

5,000 Success compounds 5 1 Rate evaluated enter trials approved

The Drug Development and Approval Process The U.S. system of new drug approvals is Administration (FDA) to begin to test the drug hospitals. Physicians monitor patients closely to perhaps the most rigorous in the world. LQSHRSOH7KH,1'VKRZVUHVXOWVRISUHYLRXV FRQ¿UPHI¿FDF\DQGLGHQWLI\DGYHUVHHYHQWV experiments; how, where and by whom the It takes 10-15 years, on average, for an New Drug Application (NDA)/Biologic new studies will be conducted; the chemical experimental drug to travel from lab to U.S. License Application (BLA). Following the structure of the compound; how it is thought SDWLHQWVDFFRUGLQJWRWKH7XIWV&HQWHUIRUWKH completion of all three phases of clinical trials, to work in the body; any toxic effects found in 6WXG\RI'UXJ'HYHORSPHQW2QO\¿YHLQ DFRPSDQ\DQDO\]HVDOORIWKHGDWDDQG¿OHVDQ the animal studies; and how the compound compounds that enter preclinical testing make 1'$RU%/$ZLWK)'$LIWKHGDWDVXFFHVVIXOO\ is manufactured. All clinical trials must be LWWRKXPDQWHVWLQJ$QGRQO\RQHRIWKRVH¿YH demonstrate both safety and effectiveness. reviewed and approved by the Institutional is approved for sale. 7KHDSSOLFDWLRQVFRQWDLQDOORIWKHVFLHQWL¿F Review Board (IRB) where the trials will be information that the company has gathered. On average, it costs a company $1.2 billion, conducted. Progress reports on clinical trials Applications typically run 100,000 pages or including the cost of failures, to get one new must be submitted at least annually to FDA and more. The average review time for the 26 new medicine from the laboratory to U.S. patients, the IRB. medicines approved by the FDA in 2010 was DFFRUGLQJWRDVWXG\E\WKH7XIWV&HQWHU Clinical Trials, Phase I. These tests usually 14.1 months. for the Study of Drug Development. involve about 20 to 100 healthy volunteers. The Approval.2QFH)'$DSSURYHVDQ1'$RU 2QFHDQHZFRPSRXQGKDVEHHQLGHQWL¿HGLQ WHVWVVWXG\DGUXJ¶VVDIHW\SUR¿OHLQFOXGLQJWKH BLA, the new medicine becomes available the laboratory, medicines are developed as safe dosage range. The studies also determine for physicians to prescribe. A company must follows: how a drug is absorbed, distributed, metabo- continue to submit periodic reports to FDA, OL]HGDQGH[FUHWHGDVZHOODVWKHGXUDWLRQRI Preclinical Testing. A pharmaceutical com- including any cases of adverse reactions and its action. pany conducts laboratory and animal studies appropriate quality-control records. For some to show biological activity of the compound Clinical Trials, Phase II. In this phase, medicines, FDA requires additional trials against the targeted disease, and the com- controlled trials of approximately 100 to 500 (Phase IV) to evaluate long-term effects. pound is evaluated for safety. volunteer patients (people with the disease) Discovering and developing safe and effective assess a drug’s effectiveness and determine Investigational New Drug Application (IND). QHZPHGLFLQHVLVDORQJGLI¿FXOWDQGH[SHQVLYH WKHHDUO\VLGHHIIHFWSUR¿OH After completing preclinical testing, a company process. Biopharmaceutical companies invested ¿OHVDQ,1'ZLWKWKH86)RRGDQG'UXJ Clinical Trials, Phase III. This phase usually an estimated $67.4 billion in research and involves 1,000 to 5,000 patients in clinics and development in 2010.