With $38 million in Series B money, Civitas Therapeutics Inc.’s can finish its ongoing, 80-patient Phase IIb trial testing inhaled levodopa (L-dopa) in Parkinson’s disease patients, and get ready for a Phase III trial that would begin in the second half of next year.
“We’re absolutely prepared to do it on our own,” said Glenn Batchelder, CEO and co-founder of Chelsea, Mass.-based Civitas, adding that the company likely will handle commercializing the compound, too, in the U.S., though a partner in Europe and Asia would be “very helpful, and that’s how we would think about launching in other geographies.”
CVT-301, an inhaled formulation of levodopa (L-dopa) being developed for fast relief from debilitating motor fluctuations in Parkinson’s, is based on powders with very low dispersion energy so that they “fly into the deep lungs” with very small pressure, Batchelder told BioWorld Today. “You put a capsule in the chamber [of the device], click it shut and inhale.”
The device used consists of seven plastic parts, two springs and a staple. Inhaling “causes the capsule to spin, and this draws the powder into the lung,” Batchelder said. “There’s no coordination required. Because of how easily these powders disperse, whether you are breathing forcefully or very lightly, you still get the same dose.”
More than 70 percent of Parkinson’s patients take the dopamine precursor L-dopa orally, which has been on the market for decades. “You need to be above a particular therapeutic threshold, and at a very small drop in blood levels, there’s a very profound drop in motor function,” Batchelder said. “It feels, to the patient, as if their symptoms are tumbling down upon them. This happens more rapidly as the disease progresses.”
Complicating the matter is that oral L-dopa is not always absorbed at the same rate or to the same degree. “There’s a small part of the intestine it’s actively transported across,” he said. As a large neutral amino acid, “if it’s hung up in the stomach [because it’s competing with proteins in food], it doesn’t get in, and if it doesn’t get across that part of the intestine, it doesn’t get in,” either.
The upshot is that patients “don’t know whether it’s going to get into the blood in 20 minutes, 40 minutes, 90 minutes, or not at all,” Batchelder said. “You end up with a very challenging situation, and that’s where our product comes in.”
As soon as patients get a hint that their oral medication is wearing off, which “might be that their tremor starts to come back, or maybe they get a cognitive fogginess, or sense of anxiety – some symptom starts to tell them,” Civitas’ inhaler could “bump their plasma levels back up to their therapeutic threshold, and bridge them over to their next oral dose of L-dopa,” he said.
For now, Parkinson’s patients are constrained in their activities, because they can never be certain when they will have what physicians call an “off” period, when the oral drugs give way to symptoms.
“They could take their kids to school, go to the supermarket, go out with friends to dinner, and find themselves trapped there,” Batchelder said. “This unpredictability is what changes patients’ lives.”
A consultant for Civitas compared the approach with CVT-301 to “filling in the potholes with the substrate that is the backbone of almost all of these patients’ existing therapy,” he said, whereas other companies seeking to provide relief attempt to “pave a smoother road” with a different compound.
Spun out from Alkermes Inc., of Waltham, Mass., Civitas raised $20 million in its Series A at the start of 2011. The delivery method for the L-dopa product grew out of Alkermes’ pulmonary delivery technology, which was the focus of a deal with Indianapolis-based Eli Lilly and Co. that Alkermes lost in 2008. (See BioWorld Today, March 10, 2008, and Jan. 10, 2011.)
When Lilly nixed its arrangement to develop and commercialize AIR inhaled insulin, Alkermes was close to filing a new drug application. Inhaled insulin wasn’t doing well in general. New York-based Pfizer Inc. in October 2007 abandoned its inhaled insulin Exubera, and Novo Nordisk AS, of Bagsvaerd, Denmark, discontinued its partnership with Hayward, Calif.-based Aradigm Corp. on another inhaled insulin, AERx iDMS. (See BioWorld Today, Oct. 19, 2007, and Jan. 16, 2008.)
Bay City Capital led Civitas’ latest round, joined by new investors RA Capital and an undisclosed public investment fund, with participation from all existing investors, including Alkermes, Canaan Partners, Fountain Healthcare Partners and Longitude Capital.