The approval of new substances could revolutionize the treatment of Alzheimer's disease. Investors can also participate in the emerging era, Pascal Mischler writes in his analysis for finews.first.
This article is published on finews.first, a forum for authors specializing in economic and financial topics.
Alzheimer's Disease (AD) is one of the biggest challenges in our aging society. Despite huge efforts during the past two decades, drug development for AD has been proven to be extremely challenging. Thus, the approval of the first disease-modifying agents Aduhelm (from Biogen) and Leqembi (from Eisai) to treat Alzheimer's Disease (AD) has been generating a lot of sparks in the AD community. Clinical data from these two drugs together with the latest results of a third drug, Lilly’s investigational drug donanemab, could be the start of a new era where we finally have tools to change the course of the disease.
The failure of most AD clinical trials to demonstrate efficacy has prevented new drugs from reaching commercialization. The approval of Biogen’s drug Aduhelm (aducanumab) by the US Food and Drug Administration (FDA) in 2021, provided a strong signal. However, optimism about the new treatment was short-lived and vanished in 2022, when the U.S. Centers for Medicare & Medicaid Services decided to limit the reimbursement coverage of the drug only to patients participating in the clinical studies required to confirm its efficacy and safety profile.
«This breakthrough will serve as a catalyst to unlock new research activities»
A few months later, there was again a reason for optimism. The FDA approved the second disease-modifying drug, Leqembi and there seems to be a consensus that the Leqembi approval is one of the biggest milestones for AD treatments for decades. This breakthrough will serve as a catalyst to unlock new research activities, provide direction and build the base for combination trials.
In the CLARITY AD trial, lecanemab (Leqembi), met primary and all key secondary endpoints proving its efficacy. The trial involved 1,795 early AD patients and showed highly statistically significant results, reducing disease progression by 27% (CDR-SB). The slowdown of disease progression means more time in less severe stages of AD.
There is still some uncertainty because Lequembi also has side effects»
But here, too, there is still some uncertainty because Lequembi also has side effects. The biggest side effect of Leqembi is called ARIA (oedema and/or hemorrhage in the brain). The right approach to dealing with ARIA will determine how well the drug will be adopted in the market. Recently, Eli Lilly announced positive results of the Trailblazer-ALZ 2 clinical trial showing that donanemab, an investigational amyloid plaque targeting therapy, slowed cognitive and functional decline by 35% in people with early symptomatic AD. The negative side effect ARIA is also a concern with this therapy.
The increasing complexity of AD starts to be reflected in the R&D pipeline projects, and with further developments of biomarkers (especially in the blood) completely new possibilities for patient stratification and drug development will be unfolded. While in Phase 3, there is still a lot of focus on the amyloid plaques, Phase 2 pipelines (82 drugs) focus on a wide variety of mechanisms such as Tau-tangle targeting, inflammation, neurotransmission, metabolism, and vascularization to name a few.
Just to highlight one area specifically: GLP-1‘s (today all over in the press as obesity and diabetes drugs) have the potential for significant anti-inflammatory effects in Alzheimer’s Disease.
«This breakthrough will serve as a catalyst to unlock new research activities»
AD is extremely complex. Nevertheless, it feels that things are coming together so that we soon could see major advances. The current status/The recent developments remind(s) us of the dawn of immune oncology from 2012-2013. There, after decades of failure, the first successful PD-1 trials ignited the creation of a whole new discipline in marketed oncology drugs. This is great for patients and their families as well as compelling for investors.
For active investment managers specializing in the healthcare sector, the AD space has started to offer compelling investment opportunities beyond the major pharmaceutical names. A deep understanding of the subject matter and the competitive landscape is indeed a prerequisite to capitalize on such opportunities and benefit from them.
Pascal Mischler is the CEO of Swiss asset manager Kieger, which focuses, among other things, on the healthcare sector. Previously, he was Country Head of Goldman Sachs Asset Management in Switzerland for 12 years. In his early career, he worked as a stock trader in the US and at the Geneva Stock Exchange.
Previous contributions: Rudi Bogni, Peter Kurer, Rolf Banz, Dieter Ruloff, Werner Vogt, Walter Wittmann, Alfred Mettler, Robert Holzach, Craig Murray, David Zollinger, Arthur Bolliger, Beat Kappeler, Chris Rowe, Stefan Gerlach, Marc Lussy, Nuno Fernandes, Richard Egger, Maurice Pedergnana, Marco Bargel, Steve Hanke, Urs Schoettli, Ursula Finsterwald, Stefan Kreuzkamp, Oliver Bussmann, Michael Benz, Albert Steck, Martin Dahinden, Thomas Fedier, Alfred Mettler, Brigitte Strebel, Mirjam Staub-Bisang, Nicolas Roth, Thorsten Polleit, Kim Iskyan, Stephen Dover, Denise Kenyon-Rouvinez, Christian Dreyer, Kinan Khadam-Al-Jame, Robert Hemmi, Anton Affentranger, Yves Mirabaud, Katharina Bart, Frédéric Papp, Hans-Martin Kraus, Gerard Guerdat, Mario Bassi, Stephen Thariyan, Dan Steinbock, Rino Borini, Bert Flossbach, Michael Hasenstab, Guido Schilling, Werner E. Rutsch, Dorte Bech Vizard, Adriano B. Lucatelli, Katharina Bart, Maya Bhandari, Jean Tirole, Hans Jakob Roth, Marco Martinelli, Thomas Sutter, Tom King, Werner Peyer, Thomas Kupfer, Peter Kurer, Arturo Bris, Frederic Papp, James Syme, Dennis Larsen, Bernd Kramer, Armin Jans, Nicolas Roth, Hans Ulrich Jost, Patrick Hunger, Fabrizio Quirighetti, Claire Shaw, Peter Fanconi, Alex Wolf, Dan Steinbock, Patrick Scheurle, Sandro Occhilupo, Will Ballard, Nicholas Yeo, Claude-Alain Margelisch, Jean-François Hirschel, Jens Pongratz, Samuel Gerber, Philipp Weckherlin, Anne Richards, Antoni Trenchev, Benoit Barbereau, Pascal R. Bersier, Shaul Lifshitz, Klaus Breiner, Ana Botín, Martin Gilbert, Jesper Koll, Ingo Rauser, Carlo Capaul, Markus Winkler, Konrad Hummler, Thomas Steinemann, Christina Boeck, Guillaume Compeyron, Miro Zivkovic, Alexander F. Wagner, Eric Heymann, Christoph Sax, Felix Brem, Jochen Moebert, Jacques-Aurélien Marcireau, Ursula Finsterwald, Michel Longhini, Stefan Blum, Zsolt Kohalmi, Karin M. Klossek, Nicolas Ramelet, Søren Bjønness, Gilles Prince, Salman Ahmed, Peter van der Welle, Ken Orchard, Christian Gast, Jeffrey Bohn, Juergen Braunstein, Jeff Voegeli, Fiona Frick, Stefan Schneider, Matthias Hunn, Andreas Vetsch, Fabiana Fedeli, Kim Fournais, Carole Millet, Swetha Ramachandran, Thomas Stucki, Neil Shearing, Tom Naratil, Oliver Berger, Robert Sharps, Tobias Mueller, Florian Wicki, Jean Keller, Niels Lan Doky, Karin M. Klossek, Johnny El Hachem, Judith Basad, Katharina Bart, Thorsten Polleit, Peter Schmid, Karam Hinduja, Zsolt Kohalmi, Raphaël Surber, Santosh Brivio, Mark Urquhart, Olivier Kessler, Bruno Capone, Peter Hody, Michael Bornhaeusser, Agnieszka Walorska, Thomas Mueller, Ebrahim Attarzadeh, Marcel Hostettler, Hui Zhang, Michael Bornhaeusser, Reto Jauch, Angela Agostini, Guy de Blonay, Tatjana Greil Castro, Jean-Baptiste Berthon, Marc Saint John Webb, Dietrich Goenemeyer, Mobeen Tahir, Didier Saint-Georges, Serge Tabachnik, Vega Ibanez, David Folkerts-Landau, Andreas Ita, Michael Welti, Mihkel Vitsur, Fabrizio Pagani, Roman Balzan, Todd Saligman, Christian Kaelin, Stuart Dunbar, Carina Schaurte, Birte Orth-Freese, Gun Woo, Lamara von Albertini, Ramon Vogt, Andrea Hoffmann, Niccolò Garzelli, Darren Williams, Benjamin Böhner, Mike Judith, Jared Cook, Henk Grootveld, Roman Gaus, Nicolas Faller, Anna Stünzi, Thomas Höhne-Sparborth, Fabrizio Pagani, Guy de Blonay, Jan Boudewijns, Sean Hagerty, Alina Donets, Sébastien Galy, Roman von Ah, Fernando Fernández, Georg von Wyss, Stefan Bannwart, Andreas Britt, Frédéric Leroux, Nick Platjouw, Rolando Grandi, Philipp Kaupke, Gérard Piasko, Brad Slingerlend, Dieter Wermuth, Grégoire Bordier, Thomas Signer, Brigitte Kaps, Gianluca Gerosa, Christine Houston, Manuel Romera Robles, Fabian Käslin, Claudia Kraaz, Marco Huwiler, Lukas Zihlmann, Nadège Lesueur-Pène, Sherif Mamdouh, Harald Preissler, Taimur Hyat, Philipp Cottier, Andreas Herrmann, Camille Vial, Marcus Hüttinger, Ralph Ebert, Serge Beck, Alannah Beer, Stéphane Monier, Ashley Simmons, Lars Jaeger, Claude Baumann, Shanna Strauss-Frank, Bertrand Binggeli, Marionna Wegenstein, George Muzinich, Jian Shi Cortesi, Razan Nasser, Nicolas Forest, Joerg Ruetschi, Reto Jauch, Bernardo Brunschwiler, Charles-Henry Monchau, Philip Adler, Brigitte Kaps, Andrew Isbester, Ha Duong, Teodoro Cocca, Beat Wittmann, Jan Brzezek, Florin Baeriswyl, and Nicolas Mousset.
