ANNUAL REPORT 2021 slide image

ANNUAL REPORT 2021

LUNDBECK ANNUAL REPORT 2021 = CONTENTS 24/111 DECENTRALIZED CLINICAL TRIALS In 2021, we maintained our COVID crisis- management plans across our portfolio of ongoing clinical trials. The goal was to provide continuity of clinical trial supplies to patients and ensure patient visits and study assessments were conducted as planned. Patient visits continued at clinics where possible and remote visits were implemented in cases where travel restrictions were in place. In 2021, we also embarked on our first pre-planned Hybrid Decentralized trial, where patients have the choice of either visiting their trial site or selecting to have remote visits in their own home setting. The first study is the Lu AG09222 phase II proof-of-concept study in migraine prevention and we had first patient visits in November 2021. Brexpiprazole-phase III in Post-Traumatic Stress Disorder (PTSD) PTSD is a psychiatric disorder that can develop as a response to traumatic events, such as interpersonal violence, combat, life- threatening accidents or natural disasters. Core features of PTSD include a variety of symptoms, such as re-experiencing phenomena (i.e. flashbacks and nightmares), avoidance behavior, numbing (i.e. amnesia, anhedonia, withdrawal, negativism) and increased arousal (i.e. insomnia, irritability, poor concentration, hypervigilance). Psychiatric co- morbidities are common, and PTSD sufferers can also present with substance abuse, mood and other anxiety disorders, impulsive and dangerous behavior and self-harm. Lundbeck and Otsuka reported positive phase II data for the combination treatment of brexpiprazole and sertraline for the treatment of PTSD in November 2018. On basis of these data, Lundbeck and Otsuka initiated two pivotal phase III trials (NCT04124614; n=577 and NCT04174170; n=733), investigating the use of brexpiprazole in combination with sertraline in the treatment of PTSD subsequent to an End of Phase II meeting with the FDA in May 2019. The execution of those two ongoing studies is challenged by the COVID-19 pandemic, primarily impacting enrollment activities and Lundbeck and Otsuka are exploring options on how best to address these COVID-19 challenges. Brexpiprazole - SNDA for treatment of schizophrenia in adolescents In December 2021, the FDA approved Lundbeck's and Otsuka's SNDA for the treatment of schizophrenia in adolescents with RexultiⓇ (brexpiprazole). More specifically, RexultiⓇ/Rxulti® is now approved for the treatment of schizophrenia in pediatric patients 13 to 17 years of age. Currently, RexultiⓇ is approved in the U.S. for treatment of schizophrenia in adults and adjunctive treatment of major depressive disorder in adults. The submission was completed one year earlier than planned, with the hope of benefitting adolescent patients with schizophrenia who need more treatment options. The acceleration of the program was made possible by doing an extrapolation analysis using data from prior studies in adult patients, pharmacokinetic results from adult and pediatric trials, and 6-month data from the ongoing open-label, long-term trial in adolescent schizophrenia patients (Trial 331- 10-236). Aripiprazole -2-Month Injectable (LAI) formulation Dosing every second month can add important benefits in terms of convenience for patients and may increase treatment adherence as well as minimizing the risk of missing doses. It may also reduce the potential need for medication monitoring by healthcare professionals, family and caregivers. In July 2019, Lundbeck and Otsuka initiated a pivotal phase 1b study (NCT04030143) to determine the safety, tolerability and pharmacokinetics of multiple-dose administrations of aripiprazole to adult participants with schizophrenia or bipolar I disorder. The study was an open-label, multiple-dose, randomized, parallel-arm, multicenter study. In addition to the assessment of safety and tolerability, the objective was to establish the similarity of aripiprazole concentrations on the last day of the dosing interval and the exposure in the last dosing interval following the final administration of aripiprazole into the gluteal muscle site. The study showed that the new 2-Month formulation was safe and tolerable, and provided effective plasma concentrations of aripiprazole for two months. No further clinical studies are expected to be required and as a next step the regulatory agencies in the U.S. and the EU will be approached. Scale-up of manufacturing capacity is progressing at Otsuka with regulatory submission gated on completing build and validation of new manufacturing capacity at Otsuka. Lundbeck and Otsuka are planning to submit the aripiprazole 2- Month injectable formulation to the EMA for MAA review by mid- 2022. In addition, Lundbeck and Otsuka will submit the New Drug Application (NDA) for review by the FDA in mid-2022.
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