The worrying number of deaths associated with Nuplazid has eyes returning to the pipeline for Parkinson’s disease. Anjali Shukla, a journalist focusing on healthcare, looks at the challenges companies face when developing a successful drug.
US regulators have decided to re-examine the safety of an already approved drug to treat Parkinson’s disease developed by San Diego-based Acadia Pharmaceuticals.
The move comes two years after the drug, Nuplazid, was approved despite hanging questions over the risk profile of the treatment. The FDA has been pushed into action following the high number of deaths reported for patients using Nuplazid.
While the outcome of the FDA enquiry is awaited, it is important to note the current supply gap for effective treatment options for the disease, which was a significant driver for the faster approval of the drug in the first place.
Nuplazid received breakthrough therapy status by the US FDA for demonstrating a substantial improvement for patients compared with already available treatment options. This also helped expedite the timeline of approvals for the drug, but the concerns regarding its safety show how important alternative treatment options are.
Parkinson’s disease: Eluding treatment
Parkinson's disease is a degenerative neurological disorder resulting from the loss of dopamine-producing brain cells. The disease mainly progresses with age and is commonly diagnosed in the early 60s.
Parkinson's disease is the second most common neurodegenerative disorder, after Alzheimer's. Available data places an estimated seven to 10 million people globally living with the disease. In the US alone, about 60,000 people are annually diagnosed with Parkinson’s disease with the number expected to double by 2040.
With an ageing global population, medical research and communities the world over will need to re-evaluate long-term care for patents as well as better management of the disease. The overall impact of neurological diseases will be equally felt both in developed and developing economies as the population grow older. Managing the economic, as well as the physical, burden of the diseases will pose a significant challenge going forward.
As communities and medical professionals the world over try to come to terms with the task of providing care to the elderly, age-related disorders have come to be a significant focus area for medical research. In 2017, there were an estimated 962 million people aged 60 years, which is 13% of the global population, according to the United Nations; the number of older people globally is estimated to grow to 1.4 billion in 2030 and 2.1 billion in 2050.
Too few treatment options
Parkinson’s disease, a progressive degenerative neurological disorder that affects movement does not have a permanent cure to date. There is also no clarity on what causes the disease except the knowledge that a genetic predisposition plays an important role. As such, there is a range of treatment options available to manage and to a certain extent control the symptoms of the disorder, but there is no permanent solution.
Levodopa, a drug developed nearly a quarter of a century ago, remains the mainstay of treatment options for Parkinson’s disease. Patients have to essentially rely on levodopa combination therapy and dopamine agonists drugs, amongst others, to treat the various symptoms related to the disorder.
The disease impacts the dopamine producing nerve cells in the brain causing tremors, muscle stiffness, impact on motor movements, and gait and balance issues. The disease also causes depression, dementia and anxiety.
The drawbacks of current treatments
However, over the years the safety and efficacy of Levodopa has raised questions and triggered concerns. It has been recorded that even though the drug and combination therapy with Levodopa and other dopaminergic therapies dramatically improve motor symptoms and quality of life for patients in the early stages of the disease, prolonged usage has shown a long list of severe side effects including speech impairment, gait and balance problems, motor fluctuations and pain. In light of these negatives, currently available therapies remain far from ideal.
In order to combat the vast array of unmet need in the Parkinson’s disease treatment space, developers are concentrating on disease modification as opposed to mere symptom relief.
The global Parkinson’s disease therapeutics market was valued at $2.18 billion in 2016. It is projected to witness an annual growth rate of more than 10.9% for the period 2017 to 2025, and will exceed $5.24 billion by 2025, according to GBI research.
This relatively high growth is owed to a rise in awareness regarding Parkinson’s disease, rapidly growing geriatric population, promising pipeline drugs, and new product launches, the report says.
However, despite steady market growth, various unmet needs remain and a cure is yet to be found. As with Alzheimer’s disease, a viable therapeutic target to halt or slow disease progression is currently not in scope due to the fact that underlying mechanisms that cause Parkinson’s disease are not fully understood.
“Most pipeline drug development programs are in their early stages, with the majority in the preclinical stage. This means that game-changing products are far from being realised, and explains why symptom-relieving therapies will continue to dominate the market through to 2021,” says Parnjeet Bains, analyst for GBI Research.
How much promise does the pipeline hold?
Over the past decade, research into new therapies for Parkinson’s disease has gathered steam, driven by the size of the market for the disorder, as well as a lack of curative treatment options. Various researches have indicated the number of people suffering with the disease is on the rise globally on the back of rapidly ageing population. With the increased incidents of disorder and the rise in the ageing population, it is more important than ever to develop newer and more effective treatment options going forward. As many as 46 new therapies to treat Parkinson’s disease are in the works, according to a recent report by PhRMA.
“New entrants are expected to offset the inevitable generic erosion caused by patent expiries, as drug developers focus their attention on offering easier methods of administration and continuous symptomatic relief,” says Bains.
Parkinson’s disease not only impacts the quality of life and the capability to carry on daily tasks but also adds a financial burden arising from expensive treatments. An estimated 37% of the patients are forced into early retirement given the impact of the disorder.
All these factors also drive the market opportunity for fresh treatment options for Parkinson’s disease. This is also an opportunity for new players to participate in developing innovative therapies to cater to the huge unmet need.
“For example, four new levodopa formulations are expected to enter the market by 2021, each designed to improve off-episodes in advanced Parkinson’s disease patients by providing continuous drug administration,” said Bains in a statement.
The lead candidates
There are several therapies in development and some of the promising ones include Prexton Therapeutics’s drug Foliglurax, currently in mid-stage trials. The treatment is being developed as an alternative approach to dopamine to control the motor symptoms for the disorder.
AstraZeneca and Takeda are jointly developing Parkinson’s disease candidate MEDI1341, alpha-synuclein antibody. MEDI1341 is an antibody of alpha-synuclein, an aggregation-prone protein shown to contribute to PD development. The antibody could prevent or delay the onset of the disorder, according to the companies. It can also potentially slow down or stop the progression of Parkinson’s disease.
Prothena Corporation’s Parkinson’s disease drug candidate, RX002/RG7935, is in mid-stage trials. The candidate, PRX002, targets α-synuclein and is being developed in collaboration with Roche as a potentially disease modifying therapy designed to slow or reduce the neurodegeneration associated with α-synuclein misfolding and/or its transmission, according to the company.
“Despite the short-term forecast for Parkinson’s disease patients, the current pipeline is very active consisting of 365 products and a diverse range of molecular targets. It includes a wide range of innovative approaches, including gene therapies and neuroprotective and neuroregenerative agents, suggesting that more effective drugs may be on the horizon,” Bains says.
The drug makers are experimenting with options that break away from being a variant of Levodopa and trying out innovative options to take on the disease including, gene therapy. The burgeoning potential pipeline of therapies for now puts the future of treatment options on a steadier path.
http://www.pharmafile.com/news/517599/parkinson-s-disease-quest-steadier-therapies
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