Apokyn (apomorphine bolus injection) / Stada, Supernus Pharma, Aguettant, Pharma San Isidro - LARVOL DELTA

APOMORPHEE: Effect of Continuous Apomorphine During the Night on Sleep Disorders in Insomniac Patients With Parkinson's Disease (clinicaltrials.gov) - P4 | N=45 | Completed | Sponsor: Clinique Beau Soleil | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Insomnia • Movement Disorders • Parkinson's Disease • Sleep Disorder • Pdss2

Initiation of Apomorphine Hydrochloride Injection (Apokyn) in the Absence of an Antiemetic in People with Parkinson's Disease (AAN 2024) - "Apo-SC is now routinely initiated in the U.S. without antiemetic pretreatment, with most PwP successfully continuing to maintenance therapy. Using a flexible dose initiation and titration strategy, backed by a comprehensive support network such as the CEP, supports successful treatment initiation."

CNS Disorders • Movement Disorders • Parkinson's Disease

Apomorphine Pump in Early Stage of Parkinson's Disease (EARLY-PUMP) (clinicaltrials.gov) - P3 | N=134 | Active, not recruiting | Sponsor: Rennes University Hospital | Recruiting ➔ Active, not recruiting | N=192 ➔ 134 | Trial completion date: Jun 2025 ➔ Jan 2025

Enrollment change • Enrollment closed • Trial completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

"FTC Rebukes Supernus Efforts To Block Sales Of Injector Pen For Use With Generic Apokyn https://t.co/FqX2wXHUAj #PinkSheet" (@PharmaPinkSheet)

Use of Real-World Data to Evaluate the Importance of Antiemetic Pretreatment for Apomorphine hydrochloride [APO, Apokyn®] subcutaneous Injection Initiation and Maintenance in People with Parkinson Disease (AAN 2023) - "All cause discontinuation within 90 days of initiation also remained largely constant across the 3-year evaluation period (26%, 23% and 23%, respectively) and did not differ by Tigan use [23% in both Tigan users and nonusers in 2021]. Conclusions Overall, our analysis demonstrates that PwP can successfully initiate apomorphine SC injection without antiemetic prophylaxis."

Clinical • Real-world • Real-world evidence • CNS Disorders • Movement Disorders • Parkinson's Disease

Neurologists’ Likelihood of Prescribing Injectable Parkinson’s disease (PD) Therapies Increases With Education on Patient Attitudes (AAN 2023) - "The sample had n=96 physicians who had previously prescribed APOKYN® and n=104 who had not...Conclusions Neurologists may be overestimating the impact of “needle phobia" since there is a discrepancy between PD patients’ willingness to self-inject medications and neurologists’ perceptions. Educating neurologists about actual patient acceptance of injectable therapies appeared effective, might facilitate more discussions about injectable therapies with patients who have troublesome off time, and may result in greater utilization of these effective therapies."

Clinical • CNS Disorders • Movement Disorders • Parkinson's Disease

"Envision a device the size of a subq insulin pump with med cartridges like Apokyn pen injector replacing oral medication. Solving the oral medication issues with a minimally invasive patient managed device." (@M_Ben_Yehuda)

Clinical

Use of On-Demand Treatments for OFF Episodes in Parkinson’s Disease: Guidance from a RAND/UCLA Modified Delphi Consensus Panel (MDS-PAS 2022) - "Objective: Develop consensus on the use of on-demand treatments (levodopa inhalation powder, apomorphine sublingual film, apomorphine subcutaneous injection) for OFF episodes in patients with Parkinson's disease (PD)... In most evaluated scenarios, panelists agreed on-demand treatment is appropriate for PD patients with OFF episodes. The greater the functional impact of OFF episodes, the more likely panelists agreed that on-demand treatment is appropriate to prescribe. On-demand treatment was also considered appropriate in patients whose OFF episodes do not interfere with daily activities but impact their lives in other ways (e.g., job performance, fear of leaving home)."

CNS Disorders • Parkinson's Disease

SUPERNUS PHARMACEUTICALS, INC. Management’s Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) (Market Screener) - "Trokendi XR net product sales decreased by 13% to $62.8 million for the three months ended March 31, 2022 as compared to the same period in 2021. This decrease was attributable primarily to the decline in unit demand offset by the price increase taken in January 2022. APOKYN net product sales decreased by 15% to $18.4 million for the three months ended March 31, 2022 as compared to the same period in 2021. This decrease was primarily attributable to the decline in unit demand due to competitive headwinds."

Sales • CNS Disorders • Migraine • Pain • Parkinson's Disease

"And how does a patient obtain just the pen without an Apokyn prescription?" (@DreamPharmD)

Clinical

Approved first generic for Apokyn injection cartridges requires separately packaged pen (FDA) - "The U.S. Food and Drug Administration has approved the first generic of Apokyn (apomorphine hydrochloride injection) drug cartridges to treat hypomobility 'off' episodes ('end-of-dose wearing off' and unpredictable 'on/off' episodes) associated with advanced Parkinson’s disease."

ANDA • CNS Disorders • Parkinson's Disease

A deep eutectic-based, self-emulsifying subcutaneous depot system for apomorphine therapy in Parkinson's disease. (PubMed, Proc Natl Acad Sci U S A) - "In vivo pharmacokinetics studies in rats and pigs further confirmed the extended release and improvement over the clinical comparator Apokyn. In vivo pharmacokinetics, supported by a pharmacokinetic simulation, demonstrate that the deep eutectic formulation reported here allows the maintenance of the therapeutic drug concentration in plasma in humans with a dosing regimen of approximately three injections per week compared to the current clinical practice of three injections per day."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

A Randomized Trial Assessing the Safety, Pharmacokinetics, and Efficacy During Morning Off of AZ-009. (PubMed, Mov Disord) - "AZ-009 appears to be a rapid-acting and reasonably well-tolerated formulation for treating off periods."

Clinical • Journal • PK/PD data • CNS Disorders • Movement Disorders • Parkinson's Disease

Supernus Announces Third Quarter 2021 Financial Results (GlobeNewswire) - "Supernus Pharmaceuticals, Inc...today reported financial results for the third quarter of 2021, and associated Company developments....Third quarter 2021 net product sales were $145.5 million, compared to $152.1 million in the same period in 2020. The decrease was primarily due to a decrease in net product sales of APOKYN and Trokendi XR..."

Sales • CNS Disorders • Migraine • Pain • Parkinson's Disease

Apomorphine Pump in Early Stage of Parkinson's Disease (EARLY-PUMP) (clinicaltrials.gov) - P3; N=192; Recruiting; Sponsor: Rennes University Hospital; Trial completion date: Sep 2024 ➔ Jun 2025; Trial primary completion date: Mar 2023 ➔ Dec 2023

Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

Pharmacokinetics and Comparative Bioavailability of Apomorphine Sublingual Film and Subcutaneous Apomorphine Formulations in Patients with Parkinson’s Disease and “OFF“ Episodes: Results of a Randomized, Three-Way Crossover, Open-Label Study. (PubMed, Neurol Ther) - P2 | "In patients with PD and "OFF" episodes, APL demonstrated lower C and relative bioavailability but similar exposures (AUCs) versus SC apomorphine within the approved dose range."

Clinical • Journal • PK/PD data • CNS Disorders • Movement Disorders • Parkinson's Disease

Etude pharmacocinétique de l’apomorphine en perfusion sous-cutanée continue diurne chez le patient parkinsonien équilibré sous traitement (clinicaltrialsregister.eu) - P4; N=20; Ongoing; Sponsor: CHU Rennes

Clinical • New P4 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

[VIRTUAL] “Needle Phobia” in Patients with Parkinson’s Disease (PD) Experiencing OFF Episodes is Uncommon (AAN 2021) - "Of those, 89% (3615/4063) answered “yes” to the question “During OFF times, would the patient be willing to consider using a pen device to get moving again?” Among participants who indicated the patient’s willingness to use a pen device, 68.9% were patients and 31.1% were next of kin or caregivers; 64.5% indicated that the patient had been diagnosed with PD for ≥7 years; and 39.6%, 21.2%, 20.7%, 13.2%, and 1.9% indicated that the patient was currently taking dopamine agonists, MAO-B inhibitors, amantadine, COMT inhibitors, and APOKYN, respectively. This survey demonstrates that 89% of patients with problematic OFF episodes would be willing to self-inject, when there is an associated benefit. Physicians may be overestimating the extent of “needle phobia.” Discussion of invasive therapies requiring injection is appropriate with most patients who have troublesome OFF time."

Clinical • CNS Disorders • Parkinson's Disease

Dr. Stuart Isaacson, CONy Virtual 2020 (YouTube) - "Dr. Stuart Isaacson...Apomorphine infusion should be used before surgical therapies are considered?"

Video

Supernus Announces Third Quarter 2020 Financial Results (GlobeNewswire) - "Commercial Update: Third quarter 2020 net product sales were $152.1 million, 52% higher than the same period in 2019, driven by the addition of $40.9 million of net product sales from the acquired commercial products...Net Product Sales ($ in millions): APOKYN: 34.5...XADAGO: 2.3....SPN-820 - Novel first-in-class activator of mTORC1: Preclinical and development activities are ongoing, with the goal of initiating a Phase II clinical program in treatment-resistant depression by the end of 2021."

New P2 trial • Sales • CNS Disorders • Depression • Multiple System Atrophy • Parkinson's Disease

Episode 8: Levodopa Inhalation Powder for OFF Episodes in Parkinson’s Disease (NeurologyLive) - "Daniel E. Kremens, MD, JD: There are other on-demand therapies aside from apomorphine. Recently in the United States, we had levodopa inhaled powder [Inbrija] approved for the treatment of OFF episodes...Rajeev Kumar, MD: Inbrija is an interesting medication in that it's levodopa without carbidopa. It's a relatively small dose, about 84 mg of levodopa, and results in 50 mg of absorbable levodopa. It's about the equivalent of taking half of an immediate release Sinemet [carbidopa/levodopa] 25/100 mg tablet in terms of the amount of levodopa administered."

Interview • Video

Episode 7: Continuous Subcutaneous Apomorphine Infusion in Development for OFF Episodes in Parkinson’s Disease (NeurologyLive) - "Daniel E. Kremens, MD, JD: There's a form of apomorphine that's available in Europe, not used as an on-demand therapy, but as a continual treatment for Parkinson's disease. It's a subcutaneous infusion...Rajeev Kumar, MD: Sure. [Apomorphine] subcutaneous infusion has been available in Europe for more than 20 years. I briefly used it experimentally as a Fellow in movement disorders. In the last 4 years approximately, we've done long-term open-label studies in the United States. I've had several patients in clinical trials receiving [apomorphine] subcutaneous continuous infusion with a pump similar to an insulin infusion pump and much tinier than the pump used for Duopa [carbidopa/levodopa] therapy."

Interview • Video

Episode 3: Apomorphine Subcutaneous Injection: Efficacy and Administration for Off-Episodes in Parkinson Disease (NeurologyLive) - "Rajeev Kumar, MD: When people would take something that they shouldn't have taken-for example, in the 1950s-apomorphine could be administered and they would vomit. If you have ever been exposed to it, it can make you puke pretty nicely. Daniel E. Kremens, MD, JD: Right. As you pointed out, for most people, when we're using apomorphine, we have them premedicate for 3 days before starting with Tigan [trimethobenzamide]. Then the majority of the patients after they've been exposed to Apokyn [apomorphine hydrochloride], even for a brief period-eg, a couple of weeks-are able to titrate off the Tigan [trimethobenzamide]. The studies went out to about 2 months, but in the real world, I often have patients on it for 2 weeks. Then, if they're using their Apokyn [apomorphine hydrochloride] regularly by that point, they no longer need their Tigan [trimethobenzamide]."

Video

Episode 4: Apomorphine Subcutaneous Injection: Patient Selection for Off-Episodes in Parkinson Disease (NeurologyLive) - "Daniel E. Kremens, MD, JD: When you think about different patients in your practices who've used Apokyn [apomorphine hydrochloride], I've had success with patients who are the very busy working person all the way to somebody you wouldn't necessarily think was an Apokyn [apomorphine hydrochloride] patient....Rajeev Kumar, MD...we were using Apokyn [apomorphine hydrochloride] a lot, and it was often an indicator. If a patient had to use Apokyn [apomorphine hydrochloride] a lot and was having a lot of off-episodes that were troublesome, that was an indicator that you should consider a device-aided therapy like deep-brain stimulation. Even now that is a reasonable indicator."

Video

Episode 5: Apomorphine Subcutaneous Injection: Circle of Care Program for Off-Episodes in Parkinson Disease (NeurologyLive) - "Daniel E. Kremens, MD, JD: We've talked about some of the advantages and great results we've had with this drug [apomorphine hydrochloride], but it's not for everybody. There are disadvantages. I know many of my patients are reluctant to use needles. There is also a societal stigma that surrounds needle use as well, and I find that to be a challenge for a lot of patients. It's not necessarily the physical use of the needle...Rajeev Kumar, MD: I agree with that. It's interesting. I call that needlephobia. It's very interesting. When I've talked to many neurologists and patients, if the concept of using a needle is approached in the correct way, then it's amazing how accepting the vast majority of patients are of using a needle to get back on again-when it improves quality of life. It's a very easy thing to administer, and it's not so scary once you've tried it."

Video