By admin 
For Amylyx Pharmaceuticals, the upcoming months represent a critical inflection point. Led by co-CEOs Justin Klee and Joshua Cohen, the company became a household name in the biotech sector not just for its rapid rise, but for its unprecedented decision-making. In early 2024, Amylyx took the rare and widely lauded step of voluntarily pulling its ALS medication, Relyvrio, from the market. This decision followed the failure of the Phase 3 PHOENIX trial, which demonstrated that the drug did not significantly outperform a placebo in slowing the progression of Amyotrophic Lateral Sclerosis. The move was hailed as a landmark moment for corporate ethics in an industry often criticized for prioritizing profits over patient outcomes. However, the withdrawal of Relyvrio left a cavernous hole in Amylyx’s commercial portfolio and a lingering question: What comes next?
The answer, it seems, lies in avexitide. Later this quarter, Amylyx is expected to release data from a pivotal study evaluating this candidate as a treatment for post-bariatric hypoglycemia (PBH), a rare and often debilitating endocrine disorder. PBH is a complication that can arise after stomach-reducing surgeries, such as gastric bypass, where patients experience severe, uncontrolled drops in blood sugar following meals. These episodes can lead to loss of consciousness, seizures, and a significantly diminished quality of life. Currently, there are no FDA-approved pharmacological treatments specifically for PBH, leaving patients to manage the condition through strict dietary modifications that are often insufficient.
Avexitide, which Amylyx acquired from the embattled Eiger BioPharmaceuticals during a bankruptcy auction, is a glucagon-like peptide-1 (GLP-1) receptor antagonist. In a poetic twist of pharmacological fate, while the rest of the world is focused on GLP-1 agonists like Ozempic and Wegovy to stimulate insulin and promote weight loss, avexitide works in the opposite direction. By blocking the GLP-1 receptor, the drug aims to prevent the excessive insulin secretion that causes the dangerous "crashes" in blood sugar seen in PBH patients. For Amylyx, the success of avexitide would not only provide a lifeline to a neglected patient population but would also validate the company’s "Act II," proving that it can successfully pivot from the wreckage of its neurodegeneration program into the metabolic and endocrine space.
However, the stakes for the avexitide readout are magnified by the company’s recent history. Investors are looking for more than just a "clean" data set; they are looking for evidence that Klee and Cohen can execute a commercial launch that avoids the controversies and setbacks that plagued Relyvrio. The market’s reaction to the upcoming data will likely be binary. A positive result could catapult Amylyx back into the ranks of viable mid-cap biotech firms, while a failure would leave the company with a dwindling cash runway and a pipeline in need of a total overhaul.
While Amylyx fights for its survival, Biogen is engaged in a different kind of struggle—a battle for the hearts and minds of its shareholders. The tension between Biogen’s management and its investors regarding the future of its Alzheimer’s disease portfolio has reached a fever pitch. This friction is rooted in the "Aduhelm hangover," a period of intense regulatory and commercial turbulence following the 2021 approval of Biogen’s first Alzheimer’s drug, which was eventually discontinued due to poor uptake and controversy surrounding its efficacy.
Now, Biogen’s hopes are pinned on Leqembi, a second-generation amyloid-targeting antibody developed in partnership with the Japanese firm Eisai. While Leqembi received full FDA approval and has shown a clear, albeit modest, ability to slow cognitive decline in early-stage patients, its commercial trajectory has been slower than many on Wall Street anticipated. Investors are increasingly at odds with Biogen’s leadership over the sheer volume of resources being poured into the Alzheimer’s franchise. The skepticism is fueled by several factors: the logistical hurdles of administering the drug (which requires bi-weekly infusions), the intensive monitoring for side effects like brain swelling (ARIA), and the emergence of a formidable competitor in Eli Lilly.
Eli Lilly’s recently approved Kisunla (donanemab) presents a direct threat to Biogen’s market share. Kisunla offers a potentially more convenient dosing schedule—once-monthly infusions—and the unique proposition that patients can stop treatment once their amyloid plaques have been cleared to a certain level. This "finite treatment" model is highly attractive to both patients and payers, putting immense pressure on Biogen and Eisai to justify Leqembi’s chronic administration model.
Biogen CEO Christopher Viehbacher, who was brought in to steady the ship and diversify the company’s pipeline, has defended the Alzheimer’s strategy as a long-term play. Under his leadership, the company has implemented a "Fit for Growth" program, cutting costs in legacy areas to fund new ventures, such as the $7.3 billion acquisition of Reata Pharmaceuticals. Yet, the shadow of Alzheimer’s remains long. Analysts are questioning whether the return on investment for Leqembi will ever justify the billions spent on development and the massive infrastructure required to support its use.
The divide between Biogen and its investors also touches on the broader "amyloid hypothesis." While the FDA has signaled its acceptance of amyloid plaque reduction as a valid surrogate endpoint for cognitive improvement, many investors remain wary of the drug class’s safety profile and the real-world impact on patients’ lives. The debate is no longer just about whether the drugs work, but whether the healthcare system can—or should—absorb the massive costs associated with treating millions of elderly patients with expensive biologics that require specialized diagnostic imaging and infusion centers.
In memory clinics across the United States, the bottleneck is palpable. To prescribe Leqembi or Kisunla, doctors must first confirm the presence of amyloid through PET scans or cerebrospinal fluid analysis. These diagnostic tools are not always readily available, and the reimbursement landscape remains complex. Investors see these logistical hurdles as a ceiling on the drugs’ peak sales potential, while Biogen’s management views them as temporary growing pains in the birth of a new therapeutic category.
The divergence in perspectives is reflected in Biogen’s stock price, which has struggled to find a consistent upward trend despite the clinical successes of Leqembi. Shareholders are demanding a "Plan B" that reduces the company’s reliance on the high-risk, high-reward neurology space. They want to see more aggressive expansion into rare diseases and immunology—areas where Biogen has historical expertise but has recently been overshadowed by its Alzheimer’s ambitions.
As Amylyx approaches its moment of truth with avexitide and Biogen continues to wrestle with the commercial realities of Leqembi, both companies illustrate the fundamental tension of the modern biotech industry. It is an industry where the science is often ahead of the infrastructure, and where the moral imperative to treat rare or "untreatable" diseases often clashes with the cold, hard logic of capital allocation.
For Amylyx, the narrative is one of resilience. If avexitide succeeds, it will be a rare example of a biotech company successfully reinventing itself after a high-profile failure. It will prove that there is a path forward for companies that act with integrity when their lead assets fail. For Biogen, the narrative is one of transition. The company is trying to move past its identity as a "multiple sclerosis powerhouse" to become a leader in the new era of neurobiology, but it must do so while keeping a frustrated investor base from jumping ship.
The coming months will provide answers to the most pressing questions facing these two firms. Will Amylyx find its "Holy Grail" in the endocrine space? Will Biogen’s massive bet on Alzheimer’s finally pay off in a way that satisfies the spreadsheets of Wall Street? In the high-stakes world of drug development, the only certainty is that the data will eventually speak for itself, and the market will be there to deliver its final, unsentimental verdict. As the third quarter draws to a close, the eyes of the industry remain fixed on the clinical trial readouts and the quarterly earnings calls that will determine the future of these two pivotal players in the quest to improve human health.
