Ongentys as ‘Off’ Time Add-on Therapy in Scotland’s Health Service
The Scottish Medicines Consortium (SMC) has added Ongentys (opicapone) — an add-on oral therapy to levodopa/Dopa decarboxylase inhibitors regimens (such as carbidopa) — to the list of medications available through the country’s National Health Service (NHS) to Parkinson’s patients experiencing ‘off’ periods.
The decision comes more than five years after the therapy was approved by the European Commission for this indication and launched in the U.K.
After the commission’s approval, health authorities in each European Union member state decide separately whether to add the approved therapy to their respective public health programs, which allow patients to access treatments at low or no cost.
Notably, Scotland is the first of the four U.K. nations to provide such Ongentys’ access to eligible Parkinson’s patients.
The add-on therapy was also approved in the U.S. in 2020 for ‘off’ periods.
The SMC decision “is really good news for the 12,400 people with Parkinson’s in Scotland and their partners, family members and friends,” Tanith Muller, parliamentary and campaigns manager at Parkinson’s UK Scotland, said in a press release.
“Some people feel unable to leave their homes because they know that severe Parkinson’s symptoms could return,” Muller said, adding that “having a new NHS-approved treatment option to consider means that more people with Parkinson’s in Scotland could gain greater control of their symptoms and their lives.”
Levodopa, a mainstay Parkinson’s treatment, is a precursor of dopamine, the brain chemical messenger progressively lost in patients and essential for muscle control. It is almost always given in combination with a molecule called carbidopa to reduce its side effects; the combination therapy is sold as Sinemet.
Together, these compounds are expected to increase dopamine levels in the brain, easing Parkinson’s motor symptoms. However, levodopa’s long-term use is associated with motor fluctuations, which result from ‘off’ periods (a return of symptoms) between doses that become progressively longer.
Notably, a recent Parkinson’s UK survey showed that three quarters of people taking Parkinson’s medication experience ‘off’ periods, with their symptoms not effectively managed for about 2.5 hours every day.
Bial’s Ongentys, taken orally once a day, works to increase the amount of levodopa reaching the brain by blocking catechol-o-methyltransferase (COMT), an enzyme that breaks down levodopa in the blood. Inhibiting COMT is expected to further increase the amount of levodopa reaching the brain, thereby prolonging its effectiveness.
The therapy’s approval was based on data from more than 30 clinical trials, including two international Phase 3 trials — BIPARK-1 (NCT01568073) and BIPARK-2 (NCT01227655).
These two trials involved more than 1,000 people who had been living with a Parkinson’s diagnosis for at least three years and who experienced daily ‘off’ periods of at least 1.5 hours despite being on a stable levodopa/carbidopa regimen.
In BIPARK-1, patients were randomly assigned to one of three Ongentys doses (5, 25, or 50 mg), or to Novartis’ Comtan (entacapone) — another COMT suppressor — or to a placebo for about 3.5 months, in addition to their standard treatment.
Results showed that both the higher dose of Ongentys (50 mg) and Comtan significantly reduced the duration of daily ‘off’ periods relative to a placebo. However, unlike Comtan, Ongentys led to improvements in both patients’ perceptions of treatment efficacy and their overall health based on clinical parameters.
Data from BIPARK-2, in which patients were given either one of two doses of Ongentys (25 or 50 mg) or a placebo, were similar to those of BIPARK-1, with the add-on therapy being superior to placebo at lowering the duration of ‘off’ periods.
These benefits were maintained in long-term extension studies, in which all patients received Ongentys for a longer period. ‘Off’ periods were shortened by about two hours in both studies, regardless of patients’ initially assigned regimen.
The most commonly reported adverse events in Ongentys-treated patients in both studies included dyskinesia or involuntary jerky movements, constipation, increased levels of creatine kinase (a marker of muscle damage), low blood pressure, and weight loss.
Fiona Purchase, from Carluke, who cares for her husband Martin who was diagnosed with Parkinson’s 28 years ago, said that “it’s great to see Opicapone has been approved in Scotland but there still needs to be more options.
“It feels like any developments have been so slow for Parkinson’s and it’s such an intolerable condition to live with and affects the whole family,” she added.
“It would be great to see all the investments and work on treatments to go into Parkinson’s in a similar way as it did to coronavirus. Everybody just got their heads together and tried to get something better more quickly and that would be brilliant,” Purchase said.
She added that increasing awareness of Parkinson’s ‘off’ periods “would be really helpful,” even among health professionals who often think “the person they see in front of them at that moment is how life is, not realizing that within the hour things can be very different.”
When the medication wears off, Purchase said, “the person can be totally immobile, frozen and struggling.”
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