The days vary greatly for Ellen Maguire, 54, an artist living with Parkinson’s disease. Often, she spends hours working in her studio to create stained glass mosaics. But on other days, she feels like she’s unable to get much done, stuck in a state of feeling like she’s “moving through pudding.”
Maguire experiences the roller coaster of “on/off periods” common to many people taking Parkinson’s medication. Every three hours or so, she takes levodopa/carbidopa. On the good days, she can feel the medicine kick in quickly like magic; on the bad days, she feels little therapeutic effect.
“The off periods remind me almost every day that I have this disease,” she says. “So I focus on the day I’m in because I never know what tomorrow will bring.”
Improving an imperfect gold standard
It’s a common refrain for many Parkinson’s patients: What will tomorrow bring? Unpredictable on/off periods can greatly interfere with daily life, and are perhaps the major concern for people living with PD today. For this reason, in addition to looking for new drugs, The Michael J. Fox Foundation and the Parkinson’s field at large are hard at work to improve existing treatments so that they more consistently deliver therapeutic benefits.
The key to success: finding better ways to deliver, and then maintain, therapeutic levels of levodopa in the bloodstream. “An improved delivery method is what I’ve always hoped for,” says Maguire. “Something that would even out my days would mean everything to me.”
Since it was first prescribed for Parkinson’s in the late 1960s, levodopa has been the so-called gold standard therapy for PD. Today, people with Parkinson’s take the drug in conjunction with carbidopa, a therapy meant to prolong the life of levodopa in the bloodstream, and, in turn, its therapeutic effect. But this combination, as Maguire can attest, is still largely imperfect.
Inhaled relief from on/off periods
The good news is, the past few years in PD research have returned significant and positive clinical study results for new therapies that have been shown to lessen on/off periods in people with PD.
This spring biotech Civitas Therapeutics announced positive clinical trial results for their inhaled formulation of levodopa, called CVT-301. The Phase 2a study, funded in part by MJFF, showed that, when administered to patients in an off state, CVT-301 provided a rapid improvement in motor function.
CVT-301 is designed to work as a sort of “rescue drug” to be taken in conjunction with the traditional pill form of levodopa/ carbidopa. The idea is that patients would be able to self-medicate by taking a puff from an inhaler when they feel an off period coming on. This puff would bring the amount of levodopa in the bloodstream back to a level that provides a therapeutic effect.
The device, similar to an asthma inhaler, is small enough to fit in a jacket pocket or a purse. And it works fast — in some cases, in just five minutes. Here’s why: any drug delivered via the lungs will get into the bloodstream faster.
“Recently, MJFF committed to partially fund our Phase 2b study of CVT-301. This grant was an important milestone that helped us secure an additional $38 million of venture capital funding to support the balance of our Phase 2b trial and the initiation of our Phase 3 studies in the second half of 2014. Upon completion, we should be in a position to file for FDA approval — with the goal of having CVT-301 available to patients soon thereafter,” according to Civitas CEO Glenn Batchelder.
Other methods deliver positive clinical results
Inhaled delivery isn’t the only treatment in development. Other promising approaches in various stages of clinical testing include:
A levodopa/carbidopa intestinal gel (LCIG) delivered into the small intestine via a pump attached to the body during waking hours. In 2012, AbbVie (formerly Abbott) announced positive Phase 3 clinical results that showed the pump could reduce off periods by as much as four hours per day, while on time without dyskinesia increased by more than four hours. LCIG is already available in Europe under the brand name Duodopa.
A levodopa/carbidopa “pump patch” from Israeli drugmaker Neuroderm is a device no larger than a credit card, made up of a reservoir where the drug is stored, and a series of painless micro-needles, which pump the therapy under the skin and into the bloodstream continuously. The company shared positive Phase 1 results last spring. Not long after, MJFF announced support for a planned Phase 2 study to better understand its efficacy.
Improved pill forms of levodopa/ carbidopa could also ease on/off periods. In 2012, Intec Pharmaceuticals announced positive results from a small proof of concept study into an “accordion pill” formulation of levodopa. The pill is compressed into capsule form, then opens slowly in the stomach, providing a more continuous release of levodopa into the body. MJFF is currently funding Intec for follow-on research.
Hope for a more consistent day
“It’s encouraging that so many therapies designed to improve the delivery of levodopa into the bloodstream are currently in clinical testing,” says MJFF CEO Todd Sherer, PhD. “We look forward to working closely with these companies to drive such promising research to the next level.
“Still, there’s much work to be done to help those living with the disease today. We hear from many Parkinson’s patients about their struggles with on/off periods and dyskinesia. To be able to make a real difference for these patients, and to do so in the not-so-distant future, would be very meaningful for them.”
Patients such as Bud Coughlan, of Pride’s Crossing, Massachusetts, takes his medication every two hours. But on most days, he feels little, if any, therapeutic effect after lunchtime. He maintains a positive attitude and exercises regularly, saying, “I’ll do whatever I can do to get through my experience with PD.”
But still, there are those moments when he can’t participate in activities with his granddaughters or wife, Angie. “Something that’s even a little more consistent would change my life,” he says. “I could see my friends and family more frequently. Honestly, it would be the biggest thing I could hope for.”