Supportive Neurology: Valuing Increased Function and Improved QoL in Treatment of Non-Core Symptoms of Neurological Disease

Transcription

1 Supportive Neurology: Valuing Increased Function and Improved QoL in Treatment of Non-Core Symptoms of Neurological Disease Ginger S. Johnson, PhD Vice President Defined Health Todd Sherer, PhD Chief Executive Officer The Michael J. Fox Foundation for Parkinson's Research

2 Defined Health is pleased to present: 28 h Annual Cancer Progress Conference March 7-8, 2017 The Westin New York at Times Square BioEurope Spring 2017 March 20 22, 2017 Barcelona, Spain Defined Health will also be participating in the following industry events: Pharma CI USA Conference September 13-14, 2016 Parsippany, NJ The International Cancer Immunotherapy Conference September 25-28, 2016 New York, NY LES Annual Conference October , 2016 Vancouver, BC Bio-Europe November 7 9, 2016 Cologne, Germany SITC 2016 November 9 13, 2016 National Harbor, MD ASH Annual Meeting December 3-6, 2016 San Diego, CA Page 2

3 Supportive Neurology: Valuing Increased Function and Improved QoL in Treatment of Non- Core Symptoms of Neurological Disease What is supportive neurology? Is there a real unmet need (and how big is it)? Is this a viable commercial opportunity? What are the advances in Parkinson s Disease Supportive Neurology (and beyond) Page 3

4 How Do We Define Supportive Neurology? The concept of Supportive Neurology is the recognition, diagnosis and treatment of conditions beyond those central to and/or diagnostic of the neurological disorder. Underlying Cause of Non- Central Disease Symptoms Co-morbid Symptoms Disease-Related Symptoms Treatment- Related Symptoms Page 4

5 Is There a Real Unmet Need? Multiple Sclerosis (MS) symptoms that are hard to see include fatigue, pain, cognitive problems like memory loss or trouble solving problems, weakness, blurred vision, numbness, prickly or tingling sensations, heat sensitivity, dizziness, and bladder or bowel problems. Non-Motor Symptoms Common in MS National Multiple Sclerosis Society Brochure; National MS Society; Beiske, A: Non-Motor Symptoms in Multiple Sclerosis Page 5

6 Is There a Real Unmet Need? While dementia is the most prominent psychiatric disturbance associated with Alzheimer s disease (AD), other neuropsychiatric symptoms occur in almost all AD patients over the lifetime of their condition. Most common are affective symptoms such as depression, apathy, anxiety, and agitation, all of which are a significant burden to the patient and the caregiver. William Utermohlen s self-portraits reveal his descent into dementia over the span of nearly four decades. Lyketsos, C.G., Kozauer, N., Robins, PV Dialogues Clin Neurosci. 2007; 9(2):111-24; New York Times on the Web. Page 6

7 Is There a Real Unmet Need? Doctors are increasingly recognizing the presence and effects of other symptoms of PD that are sometimes called "non-motor symptoms" or "dopamine-non-responsive." These symptoms are common and can have a major impact on Parkinson s patients. They can include: Parkinson Clinical Guidelines; Translational Neurodegeneration20154:1; MJFox Foundation website Page 7

8 The Voice of the Patient (and Caregiver) It is incredibly frustrating. I feel that I am missing out on my life, mostly due to the fatigue. MS Patient I am unable to get refreshing sleep due to screaming in the night and awakening at all hours. PD Patient My mom cusses at me every day, usually in public, and usually loudly. I suppose I am beyond the point of being mortified. There s nothing to do but accept it with good humor. AD Caregiver??? Our patterns of sleep may be due to due to side effects of a drug never intended to influence sleep. PD patient I ve had episodes of almost total disorientation. MS Patient If it s a 10-step task [my husband] get[s] lost in about 2 or 3 and then never complete[s] the task. PD Caregiver Patient Advocacy websites and brochures If you asked me, I wouldn t be able to tell you what I had for breakfast. I forget things and it is very disruptive to a normal life. PD Patient Page 8

9 Increased Interest in Supportive Neurology Driven By Continued unmet need Advancing understanding of symptom characteristics and biology Improving clinical probability of success (symptom identification and diagnosis, identification of target responders, ability to measure effect) Expanding support structure (regulatory agencies, patient advocacy groups, non-dilutive funding) Emerging pipeline Commercial and clinical successes Providing value to address issues unique to the neurological condition Page 9

10 Clinical Success in Supportive Neurology: NUPLAZID Launched in May 2016 by Acadia Pharmaceuticals, Nuplazid (pimavanserin) is the first and only US FDA-approved treatment for symptoms of Parkinson s Disease Psychosis (PDP) Received Breakthrough Designation from the FDA; approval in 7.9 months with one P3 pivotal study using a standard scale to assess positive symptoms in schizophrenia that was adapted for PD (SAPS-PD) Efficacy for the treatment of Parkinson s Disease Psychosis comparable to (or better than) standard of care, but without an increase in motor symptoms Acadia Website; Nuplazid Website; EvaluatePharma Page 10

11 Clinical Success in Supportive Neurology: NUPLAZID Mechanism of Action: Selective serotonin 5-HT2A inverse agonist Specific binding affinity for serotonin receptors, but minimally or nonresponsive with other receptors The specificity to serotonin receptors prevents adverse sideeffects (e.g., increased motor function) produced in other antipsychotic medications when blocking the activity of the other receptors Nuplazid Website; Adis R&D Insight Page 11

12 NUPLAZID: An Expected Commercial Success 1800 Forecasted US sales of Nuplazid by Indication (in development ex-us) USD $M EvaluatePharma Annual Price ~$24,000 (USD) Schizophrenia Alzheimer's Parkinson's Page 12

13 A Small, But Growing Club of Commercial Successes in Supportive Neurology For example: Launched Jan Avanir Pharmaceuticals (subsidiary of Otsuka) First and only treatment for pseudobulbar affect (PBA), causes patients with preexisting neurological conditions (e.g., AD, PD, MS, ALS, traumatic brain injury) to have sudden involuntary outbursts of laughing or crying Peak sales est. ~$600+M in the US Launched Sept Lundbeck (via acquisition of Chelsea Therapeutics) First and only treatment for neurogenic orthostatic hypotension (NOH) caused by primary autonomic failure (e.g, PD, multiple system atrophy), dopamine beta-hydroxylase deficiency, and non-diabetic autonomic neuropathy Peak sales est. ~$600+M in the US ADIS R&D Insight; Company/product websites; EvaluatePharma Page 13

14 A Growing Supportive Neurology Pipeline AVP-786 (deuterated dextromethorphan + quinidine. Avanir) P3: AD Agitation SRX246 (V1a receptor antagonist, Azevan) P2: Irritability in HD Tirasemtiv (skeletal muscle troponin activator, Cytokinetics) P3: ALS Respiratory Function SYN120 (dual antagonist of the 5-HT6 and 5-HT2A receptors, Acorda/BioTie) P2a: PD Dementia Nelotanserin (5-HT2a inverse antagonist, Axovant) P2: Visual Hallucinations & REM Sleep Behavior Disorder in Lewy Body Dementia and PD ADIS R&D Insight Page 14

15 Todd Sherer, PhD Chief Executive Officer The Michael J. Fox Foundation for Parkinson's Research Page 15

16 Parkinson s: Constellation of Symptoms What Are the Motor Symptoms of Parkinson's Disease? People are usually more familiar with the motor symptoms of PD, as these are the signs of the disease that are noticeable from the outside. These symptoms, known as the "cardinal" Bradykinesia symptoms of PD, include: Bradykinesia (slowness of movement) slowing down and loss of spontaneous and voluntary movement Rigidity unusual stiffness in a limb or other body part Rigidity Resting tremor an uncontrollable movement that affects Resting a limb when tremor it is at rest and stops for the duration of a voluntary movement Postural instability Postural instability problems with standing or walking, or impaired balance and coordination Other physical symptoms, such as gait problems and reduced Other facial physical expression, may symptoms also occur due to the same disruption of movement that causes the better-known tremor and slowness What Are the Non-motor Symptoms of Parkinson's Disease? Doctors are increasingly recognizing the presence and effects of other symptoms of PD that are sometimes called "non-motor symptoms" or "dopamine-non-responsive." These Cognitive symptoms are impairment common and can have a major impact on Parkinson s patients. They can include: Mood disorders Cognitive impairment decline in ability to multi-task and/or concentrate and potentially decline in intellectual functioning REM Sleep Disorder Mood disorders depression and anxiety Postural hypotension Problems sleeping REM Sleep Disorder, where individuals act out their dreams Low blood pressure when standing Constipation Speech and swallowing problems Unexplained pains, drooling and smell loss Motor Symptoms of PD Non-Motor Symptoms of PD Constipation Speech & swallowing problems Pain, drooling, smell loss Page 16

17 Patients are Being Heard Page 17

18 Opportunity to Address Symptoms Related to PD, Treatment and Comorbid Disease Underlying Cause of Non- Central Disease Symptoms Co-morbid Symptoms Disease-Related Symptoms Treatment- Related Symptoms Page 18

19 Advances in PD Supportive Neurology AVP-786 (deuterated dextromethorphan + quinidine. Avanir) P3: AD Agitation SRX246 (V1a receptor antagonist, Azevan) P2: Irritability in HD Tirasemtiv (Cytokinetics) P3: ALS Respiratory Function SYN120 (Acorda/BioTie) P2a: PD Dementia Nelotanserin (5-HT2a inverse antagonist, Axovant) P2: Visual Hallucinations & REM Sleep Behavior Disorder in Lewy Body Dementia and PD ADIS R&D Insight Page 19

20 What makes a Supportive Neurology product a viable and attractive commercial opportunity? What are the advances contributing to increased probability of success (e.g., understanding of disease biology, symptom definition and measurement, patient identification, clinical/regulatory pathway)? What is the role of MJFF (and other advocacy groups)? Any advice to companies pursuing (or looking to pursue) a Supportive Neurology indication? Page 20

21 Defined Health is pleased to present: 28 h Annual Cancer Progress Conference March 7-8, 2017 The Westin New York at Times Square BioEurope Spring 2017 March 20 22, 2017 Barcelona, Spain Defined Health will also be participating in the following industry events: Pharma CI USA Conference September 13-14, 2016 Parsippany, NJ The International Cancer Immunotherapy Conference September 25-28, 2016 New York, NY LES Annual Conference October , 2016 Vancouver, BC Bio-Europe November 7 9, 2016 Cologne, Germany SITC 2016 November 9 13, 2016 National Harbor, MD ASH Annual Meeting December 3-6, 2016 San Diego, CA Page 21