23.07.2020
Quartalsergebnis Idorsia
Das Biotech-Unternehmen Idorsia (IDIA 26.9 -2.68%) arbeitet weiter an der Lancierung erster Produkte und verbessert das Ergebnis. Der Betriebsverlust verringerte sich im Jahresvergleich von 239 auf 178 Mio. Fr. Der Semesterfehlbetrag ging von 232 auf 189 Mio. Fr. zurück. Damit sind die Erwartungen der Analysten übertroffen worden. Das Management bestätigt, die Geschäftsentwicklung schreite rasch voran.
Quelle: www.fuw.ch
22.07.2020
Favoriten 2020: Auf dem Prüfstand – Idorsia
Mehr als die Hälfte des Jahres liegt bereits hinter uns, und kaum einer hätte sich an der Jahreswende vorstellen können, was die kommenden Monate bringen würden. Mit einer Pandemie war jedenfalls nicht zu rechnen. Die 10 Aktien der Favoriten-Liste wurden daher auf der Basis der Bewertungen, der Perspektiven der Unternehmen, der wirtschaftlichen Entwicklungen und der Trends an den Kapitalmärkten am Ende des Jahres 2019 ausgewählt. Die Corona-Krise hat inzwischen mehr oder weniger alles geändert – Anlass genug, um jede einzelne Aktie einem gründlichen Corona-Check zu unterziehen.
Als innovatives Biotechnologie-Unternehmen mit einer breiten Pipeline von Entwicklungen gegen unterschiedliche Krankheiten ist Idorsia kaum vom wirtschaftlichen Auf und Ab betroffen. Das ist generell eines der Hauptargumente für Investments in der Life Sciences Industrie, auch wenn es nicht immer zutrifft. Idorsia hat bislang kein einziges Medikament am Markt. Doch bereits vier Kandidaten befinden sich in klinischen Studien der Phase III, die unmittelbar vor der Zulassung durch die Arzneimittelbehörden steht.
Innovatives Schlafmittel vor der Zulassung
Am nächsten an der Zulassung ist das neuartige Schlafmittel Daridorexant. Schon zwei Studien der Phase III wurden mit positiven Ergebnissen abgeschlossen. Voraussichtlich vor Ende Jahr wird der Zulassungsantrag dann eingereicht. Sehr wahrscheinlich ist 2021 mit der Zulassung zu rechnen. 10% der Bevölkerung leiden an dauerhafter oder wiederkehrender Schlaflosigkeit. Die medikamentösen Therapien haben seit Jahrzehnten keine Innovationen erfahren. Viele Patienten vertragen die Wirkstoffe der vorherrschenden Benzodiazepin-Klasse nicht oder leiden an Nach- und Nebenwirkungen. Insofern stösst Daridorexant auf einen riesigen Markt, der nach neuen Lösungen verlangt. Es ist ein potentieller Multi-Milliarden USD Markt.
Volkskrankheit Bluthochdruck im Visier
Das gilt auch für Aprocitentan, ebenfalls in Phase III. Bluthochdruck ist eine weitverbreitete Volkskrankheit und geht häufig mit anderen Beschwerden einher. Bluthochdruck kann sogar unmittelbar zum Tod führen. Ein hoher Prozentsatz der Patienten ist jedoch gegen herkömmliche medikamentöse Behandlungen resistent. Somit tut sich ein weiterer Markt auf, der nach alternativen Therapien verlangt.
Orphan Drug-Status
Lucarestat, ebenfalls in Phase III, stellt voraussichtlich eine hocheffiziente prophylaktische Therapie für die seltene angeborene Krankheit Morbus Fabry dar, indem das Fortschreiten der Krankheit verhindert wird. Bei Morbus Fabry fehlt ein Enzym zum Abbau bestimmter Fette in den Zellen, was zu schmerzhaften und lebensbedrohlichen Symptomen in den Organen führt. Die herkömmlichen Therapien kosten, je nach Land, bis mehrere hunderttausend CHF jährlich. Bei seltenen Krankheiten, zu denen wenig geforscht wird, sind in aller Regel die Preise für neue wirkungsvolle Therapeutika sehr hoch. Darin liegt die kommerzielle Logik für therapeutische Lösungen, obwohl es nur wenig Patienten gibt. Sowohl in den USA wie in der EU wurde „Orphan Drug“-Status verliehen, was eine beschleunigte Prüfungs- und Zulassungsprozedur bedeutet. Der Status wird nur gewährt, wenn ein echter „medical need“ vorhanden ist, d.h. die Patienten in der gegebenen Therapie-Situation stark leiden und die Kostenträger extrem teure Behandlungen bezahlen müssen.
Reiche Pipeline
Auch die weiteren Entwicklungsprojekte sind hochinteressant. Cenerimod, in Phase II adressiert Lupus, eine Auto-Immunkrankheit, bei der das Immunsystem überaktiv wird und die eigenen Organe zerstört. Selatogrel, ebenfalls in Phase II, wird bei Zulassung ein wahrer Lebensretter für Betroffene von akuten Myokardinfarkten. Viele Patienten sterben in der Zeit zwischen ersten Symptomen und medizinischer Betreuung. Die Idorsia-Lösung ist für Risikopatienten, die sich im Notfall selbst mit dem Autoinjektor behandeln. Eine Innovation von beträchtlichem (pharmako-ökonomischem) Wert.
Namhafte Kooperationspartner
Zahlreiche Kooperationen mit erstklassigen Life Science Unternehmen wie Roche, der Johnson & Johnson-Tochter Janssen, dem japanischen Pharma-Unternehmen Mochida oder dem US-Biotech Neurocrine Biosciences validieren die Idorsia-Forschung. Dies zeigt sich auch darin, dass substantielle Summen fliessen, wie bereits erfolgte Vorauszahlungen von Neurocrine von 50 Mio. USD innerhalb der letzten 12 Monate. Bei dieser Kooperation geht es um ein neuartiges Mittel gegen die seltene pädiatrische Epilepsie. Neurocrine wird im zweiten Halbjahr 2020 eine Phase II Studie starten.
900 Mio. CHF Liquidität
In diesem Stadium der Unternehmensentwicklung sind die Quartalszahlen eher zu vernachlässigen, denn ein Unternehmen ohne Produkte am Markt kann nur rote Zahlen schreiben. Eine relevante Zahl ist dagegen die Liquidität und wie lange diese ausreicht, um die diversen Projekte voranzubringen. Bei Idorsia beträgt die Liquidität zum Ende des ersten Quartals 632 Mio. CHF. Durch eine Kapitalerhöhung fliessen 330 Mio. CHF zu, sodass zum Ende des ersten Halbjahres rund 900 Mio. CHF vorhanden sein dürften. Das wird reichen, um auf absehbare Zeit sorgenfrei zu bleiben.
Lockdown verzögert klinische Studien
Im ersten Halbjahr 2020 kam es allerdings zu Verzögerungen durch die Corona-Pandemie. Studien konnten nicht durchgeführt werden. Die relevanten Ausgaben sind dadurch gesunken. Am 8. Juli verkaufte JNJ ein Aktienpaket von 8,3%, das aus der Actelion-Übernahme und anschliessenden Formierung von Idorsia stammt. Angesichts der selbst für Multis wie JNJ herausfordernden Marktbedingungen sowie anstehenden Investitionen wie in Entwicklung und Produktion eines eigenen Covid-19 Impfstoffs, kann es auch zu der Entscheidung kommen, marginale Beteiligungen zu veräussern. Eine negative Einschätzung durch JNJ ist sehr unwahrscheinlich, da beispielsweise bei Aprocitentan kooperiert wird. Zudem hält JNJ unverändert eine Wandelanleihe in Höhe von 445 Mio. CHF, wandelbar in Aktien zu 11.48 CHF – entsprechend einer Beteiligung von 27,5%.
Fazit
Wie zuvor bei der Erfolgsgeschichte Actelion ist auch bei Idorsia Management und Forschung entscheidend. Bei Actelion bezog sich die Übernahme durch JNJ allein auf die erste Zulassung und den Firmennamen. Die gesamte sonstige Forschung wurde in Idorsia eingebracht. Mag sein, dass manche Entwicklungen es wider Erwarten nicht bis zur Zulassung schaffen. So ist das Pharmageschäft. Sehr wahrscheinlich ist aber auch, dass einer oder mehrere Kandidaten aus der Pipeline innovative Blockbuster werden, das heisst Multi-Milliardenumsätze p.a. generieren.
Bisher läuft es für Idorsia hinsichtlich des Fortschritts der verschiedenen Projekte bestens. Allerdings ist für Anleger Geduld erforderlich. Das volle Potential der Aktie wird sich wohl nicht bis zum kommenden Jahresende entfalten. Doch eine Fortsetzung des aufwärtsgerichteten Trends über 30 CHF hinaus erscheint realistisch. Dennoch sind jederzeit auch Rückschläge einzukalkulieren, wie bei negativen Studienergebnissen. Die höheren Kurchancen bei Biotech-Aktien wie Idorsia gehen eben auch mit höheren Risiken einher. Wer bereits 2017 bei einem Kurs von 17.60 CHF eingestiegen ist, sieht die hohe Volatilität auf dem jetzt erhöhten Niveau gelassen. Sehr wahrscheinlich ist auch, dass immer mehr Anlegern durch die Pandemie klar wird, dass Biotech-Unternehmen ganz generell ein Teil der Lösung für viele Probleme sind und deshalb auch hohe Kursgewinne bringen können. Bei einer aktuellen Market Cap von 3.9 Mrd. CHF bleibt jedenfalls noch viel Spielraum nach oben. Für Actelion bezahlte JNJ 30 Mrd. CHF. An der positiven Einschätzung zu der Idorsia-Aktie hat sich nichts geändert.
Quelle: www.schweizeraktien.net
20.04.2020
Idorsia announces positive results in the first Phase 3 study of daridorexant with improved overall sleep and daytime performance of patients with insomnia
Idorsia to host an investor webcast to discuss the first Phase 3 results today at 14:00hrs CEST
Allschwil, Switzerland – April 20, 2020
Idorsia Ltd (SIX: IDIA) today announced positive top-line results of the first pivotal Phase 3 study investigating 25 and 50 mg doses of its dual orexin receptor antagonist, daridorexant, in 930 adult and elderly patients (39.1% = 65 years) with insomnia. The study demonstrated efficacy of treatment with daridorexant on objective and subjective sleep parameters and daytime performance with no residual effect in the morning, and no evidence of rebound or withdrawal symptoms upon treatment discontinuation.
Daridorexant at both 25 and 50 mg significantly improved sleep onset and sleep maintenance as measured objectively in a sleep lab by polysomnography. Daridorexant also significantly improved subjective total sleep time as measured daily with a patient diary at home. The results were consistently statistically significant at month 1 and at month 3, indicating sustained benefit. Furthermore, treatment with daridorexant improved patients’ daytime performance from baseline at month 1 and month 3.
Jean-Paul Clozel, MD and Chief Executive Officer of Idorsia, commented:
“While we designed daridorexant to have the optimal profile for a sleep medicine, I am none-the-less stunned by the results. Once approved, by providing daridorexant to the millions of patients with insomnia, Idorsia will have a major impact on this medical, social, and economic problem. It has struck me particularly in these times of confinement that we are living through, that sleep problems are a major issue and require an extremely safe and effective drug that can be used by the many. With these results Idorsia is entering into a new era; less than 3 years since its creation, Idorsia is taking a huge step forward in delivering on the vision to become a fully-fledged biopharmaceutical company.”
Dr. Thomas Roth, PhD, Director of the Sleep Disorder and Research Center at Henry Ford Hospital, commented:
“Pharmacological treatment for insomnia should not only help patients to fall asleep quickly and to stay asleep but also address the negative impact of poor sleep on daytime functioning. I believe that the optimal way to achieve this is through blocking the action of orexin and therefore turning down overactive wakefulness seen among insomnia disorder patients. This will allow patients to sleep throughout the night, while avoiding the adverse effects, associated with many sleep medications that act through broad sedation of the brain. The excellent results seen in this Phase 3 study of 3-month duration suggests that daridorexant can fulfil this significant need for patients with insomnia.”
Guy Braunstein, MD and Head of Global Clinical Development of Idorsia, commented:
“When designing our program, we had to show the effect of daridorexant on objective sleep measures. It was also very important to us to deliver on what the patient really needs. The program therefore aimed to determine whether daridorexant improved patients’ perception of their sleep and their performance during the day. To measure this, we developed and validated a specific patient reported outcome instrument. It was a big commitment, and we were confident that if any drug could show a positive impact it was daridorexant. We knew that this information was missing from the science of sleep.”
Primary and secondary efficacy endpoints overview
Daridorexant significantly improved sleep onset as measured by a decrease in latency to persistent sleep (LPS) from baseline compared to placebo. Daridorexant significantly improved sleep maintenance as measured by a decrease in wake time after sleep onset (WASO) from baseline compared to placebo. Total sleep time subjectively (sTST) assessed daily by patients increased significantly from baseline compared to placebo. All of these sleep measures were significantly improved with both 50 mg and 25 mg daridorexant at both 1- and 3-month timepoints. The impact of insomnia on patients’ daytime performance was measured daily using the sleepiness domain score from the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) a Patient Reported Outcome (PRO) instrument, validated according to the US Food and Drug Administration (FDA) Guidance for Industry. Daridorexant improved daytime performance, as measured by patients feeling less physically and mentally tired, less sleepy and more energetic during the day. The results were significant with 50 mg and showed a numerical trend with 25 mg, at both month 1 and month 3. Overall, the primary and secondary endpoints analyses showed consistency across doses, objective and subjective endpoints, through both night and day, and the effect was maintained over time.
About safety in the study
The rate of adverse events was comparable between placebo and daridorexant at both treatment doses. Treatment-emergent adverse events (TEAEs) during the double-blind study period were reported in 37.7% and 37.7% of the patients treated with 25 and 50 mg daridorexant, respectively (34.0% for placebo). The most frequent TEAE reported over 3% incidence and higher than placebo was nasopharyngitis, headache. The number of serious adverse events were higher in the placebo group compared to the daridorexant treatment groups (25 mg, 2 patients; 50 mg, 3 patients; placebo, 7 patients). Based on independent, blinded adjudication, potential narcolepsy-like symptoms denoting excessive daytime sleepiness were balanced across all groups (four patients in total), and those describing complex sleep behavior were observed in three patients in total. There was no next-morning residual effect assessed by a visual analog scale every morning. There was no rebound insomnia, or withdrawal symptoms upon discontinuation, and no suicide, suicidal ideation or self-injury were observed.
Guy Braunstein continued:
“I want to say a big thank you to the study team, both at the investigation sites and at Idorsia and all the study participants, for delivering a comprehensive and robust study, which has given us a wealth of data to judge the strength of daridorexant. The results from this pivotal study are truly remarkable for the consistency of the benefit in sleep measures. Moreover, this is the first study to demonstrate an insomnia product can improve how the patient feels during the day. If you ask anybody who suffers from insomnia that is what they want – to sleep longer and feel better during day. Daridorexant is addressing real patient problems. The results are made even more remarkable when you see that the efficacy is achieved without compromising safety. We now look forward to the results from the second pivotal study of daridorexant 10 and 25 mg.”
Martine Clozel, MD and Chief Scientific Officer of Idorsia, commented:
“Our research team has been working on the science of orexin and orexin receptors since their first description in 1998. Our initial work led us to the conclusion that antagonism of the orexin system was the key to providing a natural sleep architecture for patients with insomnia. We did not discover daridorexant by chance – we have worked very hard preclinically and clinically to find the ideal compound to unlock this amazing potential. We wanted a dual antagonist with a rapid effect, and a duration of action sufficient for the night but short enough to avoid any negative residual activity the following morning. The results we share today have made it all worthwhile and prove that we were right to persevere for over 20 years on the project. It just shows what can be achieved with tailored drug design. I am incredibly proud of the discovery team that created daridorexant.”
Simon Jose, Chief Commercial Officer of Idorsia, commented:
“The millions of people suffering from insomnia are seeking new treatment options to help them sleep well at night and – very importantly – perform well during the day. This is the first time a sleep medicine has demonstrated not only an improvement in sleep onset and sleep maintenance, but also in daytime performance. We look forward to bringing this medication to patients with difficulty sleeping, after review by regulatory authorities. We are confident that with such a wealth of evidence we can make this unique non-sedating sleep medication a huge success and are excited by the opportunity to lead the transformation and modernization of the sleep market.”
Detailed study results will be made available through scientific disclosure at upcoming congresses and in peer reviewed publications.
About the Phase 3 registration program
The Phase 3 registration program comprises two confirmatory studies of 3-month duration, together with a 40-week extension study which has recruited around 1,800 patients with insomnia (900 in each study) from over 160 sites across 18 countries.
The confirmatory multi-center, double-blind, randomized, placebo-controlled, parallel-group, polysomnography studies assess the efficacy and safety of daridorexant on objective and subjective sleep and daytime performance parameters in adult and elderly patients with insomnia. The first study, reported here, evaluated treatment with 25 mg and 50 mg doses over 3 months, while the second study will measure treatment with 10 mg and 25 mg doses over 3 months and is expected to report results in the third quarter of 2020. The 40-week extension study will measure the effect of all three doses, generating data for long-term treatment of insomnia.
Notes to the editor
About insomnia
Insomnia is defined as a combination of dissatisfaction with sleep and a significant negative impact on daytime performance. Dissatisfaction with sleep refers to the difficulty to initiate and/or maintain sleep on at least three nights per week for at least three months, despite adequate opportunity to sleep.
Insomnia is, worldwide, the most commonly reported sleep disorder and its impact is often underestimated. In reality, it can be a distressing condition that can impair quality of life. Sleepless nights can leave people feeling irritable and out of sorts – this may affect many aspects of daily life, from studying and employment to social activities and relationships. People who suffer from insomnia may lack the energy or motivation to exercise or to take part in social activities. It can also have a significant economic impact as it increases the risk of accident and injury on the road or in the workplace, and is a leading cause of absenteeism and reduced productivity at work. People with insomnia are more likely to experience feeling down or depressed, lack concentration, and suffer from poor energy levels during the day compared with people who sleep well. In addition, worrying about sleep can cause stress and may lead to negative thought patterns which may in turn make it more difficult to sleep, setting up a vicious circle. Chronic insomnia is associated with cardiovascular and cerebrovascular diseases, and increased mortality.
The goal of treatments for insomnia is to improve sleep quality and quantity, as well as reducing insomnia-related impaired daytime performance, while avoiding adverse events and next morning residual effect. Current treatment of insomnia includes cognitive behavioral therapy, sleep hygiene recommendations, and pharmacotherapy. The most widely prescribed products on the market that are indicated for insomnia enhance the effects of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Such medications are only approved for short-term use and are associated with side effects such as next-day effects, anterograde amnesia, and risk of tolerance and dependence.
Data supporting daridorexant in insomnia
The safety and efficacy of daridorexant in adult and elderly patients with insomnia was evaluated in a comprehensive Phase 2 program, comprising two studies, one of which included zolpidem 10 mg as an active reference. Both studies showed the desired effect on sleep maintenance and onset, with a significant dose-response relationship; treatment was generally well tolerated.
The first Phase 2 study in 360 adults (ranging from 18 to 64 years), with a treatment duration of 4 weeks, showed a significant dose dependent decrease in WASO at Day 1 & 2 (average decrease of wake-time after sleep onset from baseline on the first 2 nights of treatment, measured by polysomnography). In addition, daridorexant significantly decreased LPS (latency to persistent sleep) in a dose-dependent manner. Treatment with daridorexant was generally well tolerated. There were no reports of serious adverse events related to daridorexant.
The positive findings of the second Phase 2 study, conducted in 58 elderly patients (= 65 years), were consistent with the efficacy and safety profile of daridorexant observed in the adult population. The results of this study also showed a significant decrease in WASO and LPS at Day 1 & 2 in a dose-dependent manner. Treatment with daridorexant was generally well tolerated. There were no reports of serious adverse events related to daridorexant.
Data from an extensive Phase 1 program showed an optimal pharmacokinetic and pharmacodynamic profile for a sleep medication, together with excellent safety and tolerability.
About Dr. Thomas Roth, PhD
Dr. Roth has been the Director of the Sleep Disorders and Research Center at Henry Ford Hospital in Detroit, since 1978. Dr. Roth is also a Professor in the Department of Psychiatry at Wayne State University, School of Medicine in Detroit, Michigan, and serves as a Clinical Professor in the Department of Psychiatry at the University of Michigan, College of Medicine in Ann Arbor.
After serving as president of the Sleep Research Society, and the founding president of the National Sleep Foundation (NSF), Dr. Roth became chairman of the National Center on Sleep Disorders Research advisory board. In addition, he was a member of the board of directors of the Associated Professional Sleep Societies (APSS), chaired the Association's Scientific Program Committee and the governing board of the World Federation of Sleep Research Societies.
Dr. Roth was instrumental in the formation of the Association of Sleep Disorders Center (ASDC) and served as the organization's second president. He is also the former Chairman of the World Health Organization's worldwide project on sleep and health. In addition to authoring and co-authoring numerous articles, Dr. Roth serves as past editor-in-chief of the journal Sleep. He currently sits on the editorial boards of Sleep Reviews, Stress Medicine, and Advances in Therapy and Human Psychopharmacology.
In 2002, Dr. Roth received the NSF's Lifetime Achievement Award for his accomplishments and contributions to sleep science, sleep medicine and public health. He received a Distinguished Research Award from the Sleep Research Society as well as the Nathanial Kleitman Award from the Academy of Sleep Medicine. Dr. Roth's contributions to the sleep field are expansive, ranging from prolific research productivity and scholarship to multiple national leadership positions, as well as the mentoring of many students and colleagues. Dr. Roth serves as a consultant to Idorsia.