Apofin (apomorphine) / Chiesi - LARVOL DELTA

Continuous Subcutaneous Apomorphine Infusion Sustains Efficacy in Phase 3 InfusON Trial (NeurologyLive) - "Conducted by lead author Stuart Isaacson, MD...the study included outpatients with recurrent motor fluctuations despite optimized PD medications. Participants initiated CSAI with a 1-2 mg bolus, followed by a 1mg (0.2mL)/h infusion. CSAI was then titrated in 0.5-1 mg/h increments at clinic visits (1-10 days apart) to an optimal rate based on response and tolerability (maximum 8 mg/h). Other PD medications could be adjusted to manage dopaminergic adverse effects. Researchers defined responders as those with at least 2 hours of improvement in OFF time from baseline."

Media quote

Continuous Subcutaneous Apomorphine Infusion Demonstrates Durable Effect on OFF, ON Time in Parkinson Disease (NeurologyLive) - "Led by Stuart Isaacson, MD...99 patients with PD with inadequate motor control were titrated to individualized apomorphine dose to reach best waking day efficacy without intolerable adverse events (AEs). Once the optimal infusion dose was identified, patients entered a 52-week open-label maintenance period, with primary end point of change from baseline to week 12 in daily OFF time."

Online posting

Protocol for Skin Nodule Management Related to Continuous Subcutaneous Infusion in Parkinson Disease Proposed by Expert Panel (NeurologyLive) - "The panel of movement disorder specialists and dermatologists offered a framework of suggestions for the supervision of the most common infusion-site reaction associated with these therapies....'[Infusion-site reactions] are thought to reflect an inflammatory response to infused medication, its metabolites, and/or infusion excipients,' Isaacson and colleagues wrote."

Media quote

Apomorphine subcutaneous injection for the management of morning akinesia in Parkinson's disease (Mov Disord Clin Pract (Hoboken)) - P=NA, N=215; "Apomorphine injections significantly reduced time-to-ON in PD patients experiencing delayed onset of their morning levodopa dose, and was well tolerated in most patients. After apomorphine treatment, fluctuating patients with morning akinesia experienced rapid and reliable improvement of time-to-ON."

Clinical data

Educating Patients on Signs of Parkinson Disease OFF Episodes (NeurologyLive) - "This is the best we can do for improving the quality of life of patients. Unfortunately, we don't have the cure at hand. We know Parkinson disease is often not progressive, but the motor fluctuation, dyskinesia, delay in onset of effects, and all of these things crop up as years go by. At least we have different therapeutic approaches to deal with these, as well as the possibility of experimenting in any 1 patient to see what might be better. We have some new options that have come along in therapeutics for Parkinson disease beyond the medications."

Video

Apomorphine infusion does not impair cognitive action control in Parkinson’s disease (MDS Congress 2017) - "Our results revealed no difference between M0 and M6 and strongly suggest that continuous subcutaneous apormorphine infusion does not alter cognitive action control. Both the selection and suppression mechanisms of impulsive responses were unaffected. This is in line with previous studies reporting that apomorphine is safe regarding cognitive functions."

Clinical • Biosimilar • Gene Therapies • Parkinson's Disease

Effects of continuous apomorphine infusion on motor and nonmotor symptoms in Parkinson’s disease without cognitive deterioration (EAN 2017) - "Totally, cognitively intact PD patients appear to have benefited from 6 months of add-on apomorphine pump. Motor fluctuations, pain and the bodily discomforts were decreased. Concerning the psychological aspects, apathy, anxiety and depression were stable, whereas the emotional well-being was better and the social relationship tended to increase."

Clinical • HEOR • Alzheimer's Disease • CNS Disorders • Depression • Pain • Parkinson's Disease

Place conditioning to apomorphine in rat models of Parkinson's disease (SFN 2013) - Program#/Poster#:622.08/H36; Presentation time: Tuesday, Nov 12, 2013, 4:00 PM - 5:00 PM; "The results for low dose APO showed that only the Late PD group exhibited a positive APO conditioning score....For high dose APO, Late PD rats had extensive rotation behavior...which significantly increased between the 4 and 8 pairings post-tests and was taken into consideration."

Preclinical • Parkinson's Disease

AAN 2017 – Stuart Isaacson Interview (YouTube) - "Prof. Stuart Isaacson, Editorial Board member for US Neurology, catches up with us to talk about his recent study in apomorphine subcutaneous injection to combat delayed onset of morning levodopa dose, in patients with morning akinesia. He also briefly covers the DaTscannin patients with suspected parkinsonian syndromes?"

Interview • Video

Spinal dopamine receptors continue regulating the recovered urinary function in rats following complete spinal cord transection (Neuroscience 2017) - "Thus, spinal DA modulates bladder and EUS activity via distinct receptors: DR1 are more involved in activation of the EUS and urine storage whereas DR2 are more involved in bladder activation, EUS bursting and voiding. Pharmacological manipulation of spinal DR or DA levels may become a therapeutic strategy to improve LUT functional recovery following SCI."

CNS Disorders

Apomorphine injections: Predictors of initial common adverse events and long term tolerability (Parkinsonism Relat Disord) - P=NA, N=28; No patient demographic or previous history of dopaminergic AE predicted nausea, except for baseline pre-injection nausea at baseline; Three days of trimethobenzamide, as recommended, was actually associated with more nausea than a single dose or no dose, even though a lack of association after matched analysis was found

Adverse events • Parkinson's Disease

Pharmacological MRI (phMRI) monitors therapeutic effects of electroacupuncture (EA) in nonhuman primates modeling human Parkinson’s disease (Neuroscience 2012) - Presentation time: Saturday, Oct 13, 2012, 1:45 PM - 2:00 PM ; In the MPTP-treated caudate nucleus, EA treatment attenuated apomorphine-evoked activations at the end of the 3rd months of EA treatment and apomorphine-evoked activations were slightly increased at the end of 4th months

Preclinical-animal • Parkinson's Disease

BDNF receptor blockade hinders the beneficial effects of exercise in a rat model of Parkinson´s disease (Neuroscience) - PMID: 23396085; "...a significant reduction of rotational asymmetry induced by apomorphine in the exercised parkinsonian rats. BDNF decreased in the SNc of the SED group, and exercise was able to revert that effect. Exercised groups exhibited reduced damage to the dopaminergic system, detected as a decreased drop of TH levels in SNc and CPu."

Preclinical • Parkinson's Disease

Randomized, placebo-controlled trial of trimethobenzamide to control nausea and vomiting during initiation and continued treatment with subcutaneous apomorphine (MDS 2014) - P4, N=194; NCT00489255; Sponsor: Ipsen; "Over a longer period, a significantly lower incidence was found for TBM during Period 1 (Days 1 28, p=0.025) and Period 2 (Days 29 56, p=0.005), with no difference during Period 3 (Days 57 to 84)....Results demonstrate that TBM helps reduce nausea/vomiting during the first 8 weeks of APO therapy, but is generally not required beyond 8 weeks."

Adverse events • P4 data • Parkinson's Disease