A sublingual spray of apomorphine shows promising results in a Phase 1 pilot study for the treatment of severe uncontrollable motor fluctuations in late-stage Parkinson’s disease (PD) patients, the British specialty drugmaker Renown Pharma has announced.
Apomorphine is currently the only drug approved specifically to treat “off” episodes in patients with PD. The drug is usually delivered via subcutaneous injection in a pre-filled injection pen. This method requires multiple injections per day, which can be painful and induce lesions in the injection site. Furthermore, subcutaneous injections demand a degree of skill that may be difficult for patients.
The study compared the pharmacokinetics – absorption and peak plasma concentration – of a sublingual apomorphine spray with the approved injectable formulation, and evaluated the spray’s safety and tolerability.
Researchers gave 12 healthy volunteers 2.5 mg of subcutaneous apomorphine on day one followed by increasing doses of 10, 15, 20 and 25 mg over the next four days. The spray was shown to be safe and well-tolerated, with generally mild adverse effects. The scientists found that the 25 mg dose presented comparable peak plasma concentration (within 15-20 minutes) to the injectable apomorphine. For that reason, researchers estimate that, as with the injected formulation, the sublingual spray will induce “on” in PD patients within 5 to 10 minutes. Furthermore, the therapeutic dose of sublingual apomorphine is expected to be 15-25 mg.
“Patients report that ‘off’ episodes in Parkinson’s disease are particularly debilitating, with motor impairment often associated with non-motor symptoms such as anxiety, depression, pain and fatigue,” Tony Clarke, Renown’s chief scientific officer, said in a news release. “Renown’s sublingual apomorphine spray should address all the important factors that patients want in a treatment for ‘off’ episodes.”
Besides the fast onset of “on” periods, the sublingual spray “can also be used to treat all daily ‘off’ episodes including morning ‘off,’ which is often the hardest for patients with PD to cope with,” said Clarke.
Researchers claim sublingual apomorphine may reduce the risk of dyskinesia — or difficulty in performing voluntary movements — caused by long-term standard PD medications. Clarke said it is easy to use, stays in the mouth for only a few seconds and “has a near-neutral pH in order to avoid mouth irritation.”