Advanced Parkinson’s disease: SCYOVA, a new specialty in continuous subcutaneous infusion

Résumé

SCYOVA 240 mg/mL + 12 mg/mL solution for infusion is a new specialty indicated in the treatment of Parkinson’s disease.

This is the first combination of foslevodopa and foscarbidopa, levodopa and carbidopa prodrugs.

SCYOVA is administered as a continuous subcutaneous (SC) infusion 24 hours a day, using a Vyafuser pump and SC infusion device.

When initiating treatment, it is necessary to calculate the “levodopa equivalents”, determine the hourly infusion rate and the volume of the loading dose.

Patients and caregivers should be trained in the use of the administration device, i.e.:

transfer of the solution from the bottle to the syringe which will be inserted into the pump;
setting up the perfusion system;
to the operation of the pump.

SCYOVA can be dispensed in community pharmacies, with a 65% reimbursement. A box contains 7 vials. The syringe, infusion set, vial adapter and pump are supplied separately.

En neurology, SCYOVA 240 mg/mL + 12 mg/mL solution for infusion is the first fixed combination of foslevodopa and phoscarbidopa marketed in France.

Available in town and in hospitals, SCYOVA is indicated in the treatment of Parkinson’s disease (cf. VIDAL Reco “Parkinson’s disease”) in an advanced stage with motor fluctuations and severe hyperkinesia or dyskinesia and responding to levodopa, when the available combinations of antiparkinsonian drugs have not given satisfactory results.

SCYOVA comes as a ready-to-use injectable solution packaged in a 10 mL bottle.

The composition of active ingredients for 1 mL of solution is as follows:

foslevodopa : 240 mg, corresponding approximately to 170 mg of levodopa (foslevodopa is a prodrug of levodopa);
phoscarbidopa : 12 mg (corresponding to approximately 9 mg of carbidopa (foscarbidopa is a prodrug of carbidopa).

A medication option for advanced Parkinson’s disease

The SCYOVA evaluation by the Transparency Commission (CT) rests on three main clinical studies carried out in adult patients with advanced Parkinson’s disease, with motor fluctuations insufficiently controlled by anti-Parkinsonian treatments (studies M15-736 and M15-741):

a phase III superiority study (study M15-736) comparing the foslevodopa/foscarbidopa combination administered subcutaneously (SC) as a continuous infusion over 24 hours versus levodopa/carbidopa tablet (immediate release form), randomized, double-blind, double placebo [1]. A total of 244 patients were included and 137 (56.1%) patients completed the study. The majority of study patients were men (59.8%), with an average age of 63.9 years. This study demonstrated the superiority only versus oral levodopa/carbidopa after 12 weeks of treatment based on the following criteria:
- the variation of the normalized average daily duration in state « on » without bothersome dyskinesia (primary endpoint): 2.72 hours versus 0.97 hours, an average difference of 1.75 hours (p=0.0083),
- the variation of the normalized average duration in state « off » (key secondary outcome): -2.75 hours versus -0.96 hours, or an average difference of -1.79 hours (p=0.0054);
a phase III safety study (study M15-741), non-comparative, open-label, multicenter whose objective was to evaluate the safety and safety of use (local and systemic) of the foslevodopa/foscarbidopa SC combination using continuous infusion over 24 hours for 52 weeks [2]. The tolerance population consisted of 244 patients;
a phase I bioavailability study (study M17-220) [3]open-label, single-center whose main objective was to compare the pharmacokinetics of a single dose of levodopa administered by continuous SC infusion over 24 hours compared to a dose of levodopa administered enterally over 16 hours in healthy subjects. A total of 25 subjects participated in the study.

In his opinion of January 10, 2024 [4]the CT attributed significant actual benefit (SMR) to SCYOVA in the marketing authorization (MA) indication.

On the other hand, she considers that SCYOVA does not provide any improvement in actual benefit (ASMR V).

In the therapeutic strategy, SCYOVA constitutes a medicinal option in the treatment of advanced Parkinson’s disease in patients with the characteristics of those included in studies M15-736 and M15-741 (cf. supra).

As for DUODOPA specialties intestinal gel (levodopa/carbidopa) and LECIGIMON gel intestinal (levodopa/carbidopa/entacapone), treatment with SCYOVA could be considered:

in patients not eligible for deep brain stimulation;
in case of contraindication, intolerance, failure of apomorphine in continuous subcutaneous infusion, or even as an alternative.

SCYOVA in practice: administration by continuous subcutaneous infusion

SCYOVA is administered as a continuous SC infusion 24 hours a day with the ambulatory infusion pump Vyafuser (Philips Medisize).

The recommended initial infusion rate for SCYOVA is determined by converting daily levodopa intake to “levodopa equivalents” (LE) and then increasing it to account for 24-day dosing. hours. This dose is then adjusted without exceeding one maximum daily dose of foslevodopa of 6 000 mg (or 25 mL of SCYOVA per day, corresponding to approximately 4 260 mg of levodopa per day).

SCYOVA replaces medicines containing levodopa and catechol-O-methyl-transferase (COMT) inhibitors.
If necessary, other classes of medications to treat Parkinson’s disease can be taken concomitantly.

Initiation of treatment

Three steps are required to initiate treatment with SCYOVA.

stage 1 : calculate levodopa equivalents (LE) based on levodopa-containing medications used while the patient is awake;
stage 2 : determine the hourly infusion rate of SCYOVA;
stage 3 : determine the volume of the loading dose.

These steps are described in the VIDAL monograph by SCYOVA.

Instructions: Loading the Pump and Setting Up the Infusion Set

The pump must be recharged with a new syringe within the 24-hour period to ensure sufficient medication is administered to control the symptoms.

Instructions for recharging the pump and setting up the infusion device are described in a video developed by the laboratory:

presentation of the necessary accessories: SCYOVA bottle, syringe, bottle adapter, absorbent paper, alcohol swab/pad, insertion device including cannula, infusion tubing, pump. The syringe, infusion set, vial adapter and pump are supplied separately. Absorbent paper and compress are not provided;
transfer of the solution from the vial into the syringe, using the adapter: the entire contents of a vial must be transferred at once into a syringe for administration (single-use vial). Once transferred, the product must be used within 24 hours;
placement of the syringe in the pump and connection to the tubing: the medication must be at room temperature before infusion;
setting up the SC infusion in the abdomen using the insertion device, and connecting to the tubing: change the infusion site regularly (at least every 3 days) using a new infusion set ;
instructions for starting the pump: change the battery every day;
waste management: throw the cannula, the tubing and the insertion device into a waste collector from healthcare activities with perforating infectious risk (DASRI) provided by the pharmacist.

Use by patients or the caregivers

Patients selected for treatment with SCYOVA should be able to understand and use the delivery system themselves or with the assistance of a caregiver. They must be trained in the correct use of SCYOVA and the delivery system.

A user guide for them developed by the laboratory is online at vidal.fr.