Definition
Parkinson’s disease (PD) is a chronic disorder characterized by movement abnormalities and other non-motor symptoms, such as dementia, depression, visual hallucinations, and autonomic dysfunction. Although not fatal, there is currently no cure for the disease, and its chronicity is associated with significant morbidity and disability.
Latest key takeaways
- Datamonitor Healthcare estimates that in 2018, there were 9.4 million prevalent cases of Parkinson’s disease (PD) in adults aged 40 years and older worldwide, and forecasts that number to increase to 12.4 million prevalent cases by 2027.
- In the last year there have been an array of impactful events that have occurred in the PD space. Roche released Phase II data for its novel alpha-synuclein monoclonal antibody prasinezumab, which exhibited modest efficacy, while Anavex also released data readouts from a Phase II trial investigating its novel PD dementia drug, ANAVEX 2-73, on the associated cognitive deficits experienced by patients. Data showed clinically meaningful cognitive improvements on multiple cognitive assessment parameters, as well as a reduction in motor and non-motor symptoms. In a recent Phase III study, Amneal’s IPX203, a novel formulation of both immediate-release and extended-release carbidopa and levodopa (CD-LD) granules, showed the potential of IPX203 to increase “good on” time in PD patients – higher-quality hours without troublesome and non-troublesome dyskinesia (a side effect of existing CD-LD formulations). The product decreased “off” time in patients compared to immediate-release CD/LD and showed an increase in “good on” time per dose.
- Duopa is among the most lucrative drugs currently available in the PD market. A contributing factor to the drug’s successful market penetration is the clinical efficacy data achieved in trials, where Duopa treatment significantly reduced “off” periods in PD patients compared to the standard of care, Sinemet (CD-LD). Duopa, also a CD-LD combination, is delivered directly and continuously into the intestines by a pump for up to 16 hours per day, thus reducing or even eliminating fluctuations and “off” periods. The procedure, however, is one of the most invasive in this market and comes with the usual risks of surgical complications. Duopa also has one of the highest price tags in the PD market, but since payers view its cost-effectiveness ratio positively, AbbVie looks set to maintain fruitful returns on the drug.
- Acadia’s Nuplazid, the first and only US-approved drug for Parkinson’s disease psychosis (PDP), scores well commercially in Datamonitor Healthcare’s drug assessment model. In pivotal trials, Nuplazid demonstrated significant efficacy in reducing the hallucinations and delusions associated with PDP, and through its non-dopaminergic mechanism it has shown no negative impacts on motor function. Furthermore, most other atypical antipsychotics are contraindicated for PDP, with none approved by the FDA for this specific condition. Acadia reported $441.8m in sales for Nuplazid in 2020, and this is expected to increase substantially over the coming decade given the lack of competition in this segment and the drug’s ongoing clinical development in other indications.
- Neupro has performed well commercially since its US approval in 2007, but a looming patent cliff jeopardizes the brand’s future revenues in the PD market. Several factors have contributed to the drug’s performance, including a transdermal, continuous delivery system, its targeting of both early- and late-stage PD patients, monotherapy use, and its availability across the US, EU, and Japan. In trials, the drug showed slightly lower efficacy compared to Mirapex, though despite this has established itself firmly in the PD treatment algorithm. UCB has fended off generic rivals thus far, and is currently tied up in patent litigation, but will likely face generic competition before 2023. Actavis Laboratories has received a tentative ANDA approval for its rotigotine generic, and as soon as this and any other rival generics can be launched, Neupro sales will undoubtedly see a dramatic decrease.
- Despite levodopa’s status as the drug of choice in PD, long-term use frequently results in diminished efficacy and the development of motor fluctuations and dyskinesia. Advanced PD, therefore, has the greatest opportunities for drug developers. Competition in the rescue therapy space has begun to heat up, with Inbrija and Kynmobi both approved over the past couple of years, and this segment will continue to grow as developers look to target the rapid treatment of “off” periods. Continuous infusions have also emerged to tackle this issue, mimicking the continuous release of dopamine in non-pathological conditions. These therapies have been the most efficacious in reducing “off” time and increasing quality “on” time. Developers have also incorporated complex devices/formulations to extend market exclusivity and combat generic imitations.
- Prothena has partnered with Roche to potentially bring the first disease-modifying therapy to the PD market. The drug, known as prasinezumab, is a monoclonal antibody targeting the pathological hallmark of PD, Lewy bodies, which consist of alpha-synuclein aggregates. In early trials thus far, prasinezumab has signaled strong proof of concept by inducing a mean reduction of free serum alpha-synuclein levels of 96% in healthy volunteers. Recent results from a Phase II randomized, controlled trial in early PD patients displayed statistical superiority in improvements on the Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) versus placebo, though these improvements were modest at best. This could be explained by the early PD cohort utilized in this study, presumably selected due to the lower likelihood of patients exhibiting severe and irreversible dopaminergic neuronal loss; however, the size of effect would understandably be reduced in this less severe population. The Phase IIb trial of prasinezumab in early PD patients was initiated in May 2021.
- Other promising pipeline therapies include the apomorphine infusion pump, in development by Supernus Pharmaceuticals, for the continuous treatment of on-off episodes in patients whose motor control is unsatisfactory with oral levodopa, and at least one other non-invasive PD therapy. Additionally, Datamonitor Healthcare views Mitsubishi Tanabe’s ND0612 as the antiparkinsonian agent that has the most clinical potential, and consequently it also has one of the highest-rated commercial profiles out of the drugs assessed. The drug is similar to Duopa in that it uses a constant infusion pump; however, as a subcutaneous device the treatment spares the adverse events and potential issues associated with a surgically administered device. In a Phase II trial, ND0612 demonstrated a 2.8-hour reduction in “off” periods, and 42% of patients experienced a complete reduction in “off” time (to 0 hours).
- As has been the case for many years, and despite new drug entrants, one of the greatest unmet pharmacological needs in the treatment of PD is for neuroprotective therapies to prevent disease progression. In addition to this, more tolerable drugs and regimens are needed, as well as more effective drugs for non-motor symptoms, and improved control of motor fluctuations/“off” periods.
- The majority of high-impact upcoming catalysts in the PD space comprise later-stage trial readouts for pipeline PD drugs. Topline results are expected from Pharma Two B’s Phase III trial of P2B001. Likewise, AbbVie expects Phase III trial data in Q4 2021 for its subcutaneous carbidopa/levodopa formulation, ABBV-951.
CONTENTS
7 OVERVIEW
7 Latest key takeaways
9 DISEASE BACKGROUND
9 Definition
9 Patient segmentation
9 Symptoms
10 Risk factors
11 Diagnosis
13 TREATMENT
13 Non-pharmacological treatment approaches
13 Pharmacological therapy
14 Key pharmacological treatment guideline recommendations
17 EPIDEMIOLOGY
17 Prevalence methodology
20 MARKETED DRUGS
27 PIPELINE DRUGS
40 KEY REGULATORY EVENTS
40 EMA Rejects Kyowa’s Parkinson’s Disease Drug
40 Opicapone Among Myriad New Filings In EU
40 Verily’s Study Watch Rejected By FDA As Parkinson’s Drug-Development Tool
40 Medtronic Announces FDA Approval Of SenSight Directional Lead System For Treating Movement Disorders
41 US FDA Throws Acadia A Curveball On Nuplazid For Dementia Psychosis
41 Acadia’s Nuplazid Hits A Review Roadblock, But Not A CRL (For Now)
41 Stada Launches Lecigon In Germany And Austria
43 PROBABILITY OF SUCCESS
44 LICENSING AND ASSET ACQUISITION DEALS
44 Bial Gets European Rights To Sunovion Parkinson’s Drug
44 Shape Therapeutics Signs Licensing Agreement With Roche
44 AC Immune Beefs Up Neurodegenerative Pipeline With AFFiRiS Alpha-Synuclein Portfolio
44 Ipsen Strengthens Early Clinical Pipeline With IRLAB’s Mesdepotem For Levodopa-Induced Dyskinesia
45 Contera Pharma, Abzu Ink RNA Therapeutics Partnership
45 Silo Pharma Enters Research Alliance With University Of California San Francisco
45 GSK Looks To Immuno-Neurology In $700m Alector Tie-up
46 AbbVie, Caraway Research Targets TMEM175 Mutations
46 Adhera Therapeutics Acquires Melior Pharmaceuticals
46 Core One Takes In Akome Biotech In All-Stock Deal
47 SciNeuro Gains China-Plus Rights To Lilly’s Alpha-Synuclein Antibodies
47 Genentech Forms Collaboration With University Of California San Francisco And University Of California, Berkeley
47 AbbVie Gets Option To Acquire Mitokinin
47 Macrogen, Lifex Ink Co-Research Pact For Parkinson’s Therapy
48 Lilly Broadens Its CNS Reach With Rigel RIPK1 Deal
48 Neurocrine Biosciences Terminates Parkinson’s Disease Portion Of Partnership With Voyager Therapeutics
48 Eli Lilly To Acquire Prevail For $880m
49 Adamas Concludes Gocovri Patent Dispute, Obtains Osmolex ER
49 AffaMed Licenses Parkinson’s Candidate From Kissei
49 Stada Progresses In Parkinson’s With Lobsor Purchase
50 CLINICAL TRIAL LANDSCAPE
51 Sponsors by status
52 Sponsors by phase
53 Recent events
56 DRUG ASSESSMENT MODEL
56 Marketed antiparkinsonian drugs
57 Pipeline antiparkinsonian drugs
60 MARKET DYNAMICS
61 FUTURE TRENDS
61 Older, genericized core therapies will continue to dominate market share
61 Targeting niche segments with the greatest unmet needs will be highly rewarded
63 CONSENSUS FORECASTS
67 RECENT EVENTS AND ANALYST OPINION
67 IPX203 for Parkinson’s Disease (August 25, 2021)
69 ANAVEX 2-73 for Parkinson’s Disease (November 6, 2020)
70 Prasinezumab for Parkinson’s Disease (September 11, 2020)
72 THN102 for Parkinson’s Disease (March 31, 2020)
74 Foliglurax for Parkinson’s Disease (March 27, 2020)
76 KEY UPCOMING EVENTS
77 UNMET NEEDS
77 Neuroprotective treatments that slow down or halt disease progression
77 Treatment of non-motor symptoms
77 Improved control of motor fluctuations/“wearing off” periods
77 New effective drug treatments with improved side-effect profiles
79 BIBLIOGRAPHY
81 APPENDIX
LIST OF FIGURES
10 Figure 1: Parkinson’s disease symptoms and symptom domains
19 Figure 2: Trends in prevalent cases of Parkinson’s disease, 2018–27
27 Figure 3: Overview of pipeline drugs for Parkinson’s disease in the US
27 Figure 4: Pipeline drugs for Parkinson’s disease, by company
28 Figure 5: Pipeline drugs for Parkinson’s disease, by drug type
28 Figure 6: Pipeline drugs for Parkinson’s disease, by classification
43 Figure 7: Probability of success in the Parkinson’s disease pipeline
50 Figure 8: Clinical trials in Parkinson’s disease
50 Figure 9: Top 10 drugs for clinical trials in Parkinson’s disease
51 Figure 10: Top 10 companies for clinical trials in Parkinson’s disease
51 Figure 11: Trial locations in Parkinson’s disease
52 Figure 12: Parkinson’s disease trials status
53 Figure 13: Parkinson’s disease trials sponsors, by phase
56 Figure 14: Datamonitor Healthcare’s drug assessment summary for Parkinson’s disease
60 Figure 15: Market dynamics in Parkinson’s disease
61 Figure 16: Future trends in Parkinson’s disease
69 Figure 17: IPX203 for Parkinson’s Disease (August 25, 2021): Phase III – vs. IR CD-LD
70 Figure 18: ANAVEX 2-73 for Parkinson’s Disease (November 6, 2020): Phase II – PD Dementia (PDD)
72 Figure 19: Prasinezumab for Parkinson’s Disease (September 11, 2020): Phase II – PASADENA
74 Figure 20: THN102 for Parkinson’s Disease (March 31, 2020): Phase II – THN102-202
75 Figure 21: Foliglurax for Parkinson’s Disease (March 27, 2020): Phase II – AMBLED (Europe)
76 Figure 22: Key upcoming events in Parkinson’s disease
LIST OF TABLES
14 Table 1: Major approved treatments for Parkinson’s disease
18 Table 2: Prevalent cases of Parkinson’s disease, 2018–27
21 Table 3: Marketed drugs for Parkinson’s disease
29 Table 4: Pipeline drugs for Parkinson’s disease in the US
64 Table 5: Historical global sales, by drug ($m), 2016–20
66 Table 6: Forecasted global sales, by drug ($m), 2021–25
67 Table 7: IPX203 for Parkinson’s Disease (August 25, 2021)
69 Table 8: ANAVEX 2-73 for Parkinson’s Disease (November 6, 2020)
71 Table 9: Prasinezumab for Parkinson’s Disease (September 11, 2020)
73 Table 10: THN102 for Parkinson’s Disease (March 31, 2020)
74 Table 11: Foliglurax for Parkinson’s Disease (March 27, 2020)