According to statistics from the Centers for Disease Control and Prevention, Parkinson's disease, or PD, was the 14th leading cause of death in 2010. Despite being a disease that garners 60,000 new diagnoses each year in the United States and has approximately 1 million sufferers based on estimates by the Parkinson's Disease Foundation, you don't hear nearly enough about what's being done to improve patient quality of life.
Source: Centers for Disease Control and Prevention. Death rate per 100,000 people.
The sad truth is that this debilitating disease -- characterized by a progressive degradation of the central nervous system that leads to involuntary muscle movements and dementia in its later stages -- has no cure. Although physicians have found certain drug combinations that can reduce symptoms of the disease, there are still far more questions than answers when it comes to treating Parkinson's patients, and many of the later-stage symptoms, such as dementia and hallucinations, simply don't have a targeted therapy approved by the Food and Drug Administration.
This isn't to say that pharmaceutical companies haven't tried to break down these barriers -- it's just that they've failed miserably, unfortunately.
A long list of disappointments
Merck (MRK 1.11%) has seen two disappointments with experimental Parkinson's therapies over the past year. In May, the company shelved its experimental A2A receptor agonist preladenant after three late-stage studies (two in combination with standard levodopa and one as a monotherapy) failed to induce a placebo-topping response. Also, as FierceBiotech pointed out, just a month prior to its preladenant disappointment it also backed out of a licensing agreement with Cerecor for an NR2B antagonist known as MK-0657.
Merck isn't alone, though. Impax Laboratories (IPXL +0.00%) and international licensing partner GlaxoSmithKline have had a world of trouble trying to bring its idiopathic PD drug, Rytary, to market. Rytary has been in front of the FDA twice now, and it's been rejected twice with manufacturing concerns being the decisive factor each time. In other words, Rytary has demonstrated potentially approvable efficacy, but repeat manufacturing deficiencies at Impax's Hayward, Calif., plant have made an approval thus far not possible.
Three pipeline hopefuls that could change the game
The good news is that there's still hope! Multiple small and large biopharmaceutical companies are pouring research dollars into therapies that alleviate symptoms and could even battle the direct cause of the disease. We've clearly seen that the deck is stacked against PD drug developers because the nature of the disease is still mostly unknown. But if there is a chance at beating it, I'd certainly say the following three drugs have a decent shot by the end of this decade.
Pimavanserin
No PD drug has had more buzz surrounding it in recent years than ACADIA Pharmaceuticals' (ACAD +5.03%) pimavanserin. It is a late-stage drug designed to treat PD-induced psychosis and, if approved, would be the first targeted therapy to do so. Based on its late-stage results, an approval may not be too far off.
In trials, pimavanserin met its primary endpoint of providing highly significant antipsychotic efficacy while also delivering on its secondary endpoint of improving motoric tolerability. Adding fuel to the fire, just weeks after announcing these trial results, the FDA allowed ACADIA to skip the need for a confirmatory phase 3 trial and file for an accelerated new drug application for pimavanserin.
This experimental drug could become a key new treatment option because the only two current treatments for PD psychosis are AstraZeneca's schizophrenia drug Seroquel and Novartis' (NVS 1.97%) Clozaril. Neither drug has been clinically shown to definitively improve PD symptoms and Clozaril usage actually comes with the potential for a rare white-blood-cell disorder known as agranulocytosis. As a targeted psychosis therapy, ACADIA's drug has the potential to greatly improve PD patients' quality of life.
Levodopa-Carbdiopa intestinal gel (Duodopa, aka LCIG)
Currently, the go-to PD drug combination is Levodopa and Carbidopa. Levodopa has been a mainstay treatment of PD patients for decades as it's able to transcend the difficult-to-treat blood-brain barrier where it's converted into dopamine. It's believed that dopamine helps improve nerve conduction, which can reduce the severity of PD symptoms. Carbidopa, on the other hand, complements Levodopa so it doesn't break down in the body before it crosses that barrier and thus reduces the quantity of Levodopa needing to be taken, reducing the nausea and vomiting side effects that were common when Levodopa was first introduced decades ago.
Duodopa, which has been developed by AbbVie (ABBV 1.20%) and is approved in Europe, is a gel form of Levodopa and Carbidopa that is injected directly into the intestines to treat advanced PD. The goal of this delivery method is to administer a dose that will last longer and be more consistent throughout the body. As my Foolish health care colleague Keith Speights notes, it has the potential to become a $1 billion drug if approved in the U.S.
In a 54-week open-label safety and tolerability study that AbbVie released the results of last year, LCIG produced only mild-to-moderate adverse events signaling a tolerable safety profile, and delivered a marked decline in average daily poor motor function and dyskinesia associated with PD. Furthermore, in phase 3 efficacy trials, LCIG produced a mean daily reduction in "poor mobility" by four hours compared to the placebo. Based on these results, I wouldn't be surprised to see LCIG approved in the U.S. sometime next year.
AFQ056 (mavoglurant)
A bit earlier in development than either pimavanserin or LCIG is Novartis' mavoglurant, which is being targeted at treating both PD levodopa-induced dyskinesia (and impairment of voluntary movements) and a rare disease known as Fragile-X Syndrome.
Mavoglurant is a metabotropic glutamate receptor 5 antagonist. In other words, it's designed to block a specific receptor (mGluR5) that is believed to maintain normal brain cell function. In cases of PD, mGluR5 is believed to be overexpressed, which leads to exacerbation of the disease. Mavoglurant would reduce that overexpression and possibly lessen symptom severity.
Currently, mavoglurant is in late-stage trials for PD levodopa-induced dyskinesia, but it has shown promise in much smaller studies. In a 13-week early stage study, mavoglurant demonstrated anti-dyskinteic efficacy relative to the placebo with patient motor functions not worsening. I'd probably suggest sticking to the sidelines until we get those late-stage results, but its early stage success has certainly been encouraging.
