Novo Nordisk plunged 27% this month—the worst monthly performance in over two decades. What challenges is the company facing?

On October 9, 2025, Novo Nordisk announced a definitive agreement to acquire Akero Therapeutics for $54.00 per share in cash, totaling $4.7 billion, for all of Akero’s outstanding common stock. In addition, Akero’s shareholders will receive non-transferable contingent value rights (CVRs). If Akero’s lead drug, efruxifermin (EFX), receives U.S. regulatory approval for the treatment of compensated cirrhosis by June 30, 2031, CVR holders will receive an additional $6.00 per share in cash—approximately $500 million in total. Thus, the total potential value of this acquisition could reach $5.2 billion in cash—a premium of approximately 32% over Akero’s 30-day volume-weighted average price (VWAP). This transaction marks Novo Nordisk’s largest acquisition in recent years, aimed at reinforcing its leadership in metabolic diseases—particularly in the rapidly growing market for metabolic dysfunction–associated steatohepatitis (MASH). To date, Akero’s innovative EFX program is among the leading efforts to develop a best-in-class therapy for MASH. Notably, over 40% of MASH patients have type 2 diabetes, and 80% are overweight or obese—conditions highly aligned with Novo Nordisk’s core obesity-treatment business. If approved, EFX could be used either as monotherapy or in combination with Novo Nordisk’s Wegovy (semaglutide injection), creating a potentially “game-changing” therapeutic regimen. It would also synergize with Novo Nordisk’s semaglutide platform, jointly expanding into the overlapping MASH–obesity market. This move is also widely viewed as a direct competitive response to rivals such as Roche and Eli Lilly. Amid intensifying competition in the weight-loss drug space—and slowing growth in key markets—Novo Nordisk has begun actively pursuing self-renewal. Under pressure from all sides: downsizing, restructuring, and restarting As first-mover advantage fades, even the global leader in anti-obesity therapeutics is struggling. Founded in 1923 and headquartered in Denmark, Novo Nordisk is a world-leading healthcare company operating in 80 countries, with approximately 78,400 employees and products sold in 170 countries. Its Class B shares trade on Nasdaq Copenhagen, and its American Depositary Receipts (ADRs) are listed on the New York Stock Exchange. Impacted by intensifying competition and recent market entry of biosimilars, Novo Nordisk’s latest quarterly financial report—released in August 2025—showed that second-quarter growth still fell short of expectations. The company lowered its 2025 operating profit growth forecast to 4%–10%, down from the prior range of 10%–16%. Notably, this marks the third time Novo Nordisk has revised its full-year guidance downward in 2025—and its share price has declined roughly 60% from its peak. Faced with mounting internal and external pressures, the multinational giant completed a CEO transition in early August 2025: Lars Fruergaard Jørgensen stepped down as President and CEO, and Maziar Mike Doustdar was appointed as his successor. The new CEO wasted no time: his first major initiative involved large-scale personnel restructuring.

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In September 2025, Novo Nordisk launched its largest organizational restructuring in a century: cutting approximately 9,000 jobs globally—about 11% of its workforce—including roughly 5,000 positions in Denmark; shutting down its cell therapy division; and terminating early-stage programs in liver disease and oncology. By September 2026, cumulative layoffs are expected to reach about 13,000, reducing the full-time workforce to 66,000. CEO Doustdar stated the goal is to “simplify the organization and accelerate decision-making,” saving approximately 8 billion Danish kroner annually—funds to be redirected toward diabetes and obesity R&D. Meanwhile, semaglutide faces patent and data exclusivity expirations across eight key markets. Its core U.S. patent expires at the end of 2032. To withstand the impending patent cliff, Novo Nordisk must sustain growth through a leaner organization and externally sourced pipeline assets. The company has significantly accelerated its development of novel peptides and macrocyclic drugs in the cardiovascular–metabolic space. On September 17, it entered a collaboration with Danish drug design firm Orbis Medicines, valued at up to $1.4 billion, to leverage Orbis’s nGen platform for developing oral macrocyclic drugs targeting cardiovascular–metabolic diseases. One day later, Novo Nordisk announced an asset purchase agreement with Kallyope to acquire three non-incretin obesity drug candidates. Jacob Petersen, Novo Nordisk’s Global Head of Research, and others first disclosed on social media that the company had signed an asset purchase agreement with New York–based biotech Kallyope, acquiring three non-incretin obesity programs. The lead candidate, K-554, is a potential first-in-class peptide already at IND-ready stage; it is accompanied by a follow-on small-molecule program, plus another small-molecule receptor agonist currently in lead optimization. Neither the transaction value nor the specific targets of the three programs have been disclosed. K-554 thus raises an intriguing question: what is the target of this newly acquired non-incretin anti-obesity peptide? 01 K-554’s target remains undisclosed—but clues point strongly to GRPR Although no official confirmation exists, tracing Kallyope’s publicly available information from the past two years back through patent databases reveals one increasingly prominent candidate target: the gastrin-releasing peptide receptor (GRPR), also known as the bombesin receptor subtype 2 (BB2). It should be emphasized upfront that the following analysis is speculative, based solely on publicly available information. Kallyope has never stated that K-554 is a GRPR agonist, nor do its patents explicitly label any specific sequence as “K-554.” Nevertheless, alignment across multiple dimensions—including project descriptions, drug format, dosing regimen, biological function, and patent timelines—makes the association between GRPR and K-554 highly compelling. When outlining its 2026 R&D plan in January, Kallyope provided some details about K-554: It is a once-weekly subcutaneous peptide therapy targeting an undisclosed “non-incretin peptide receptor” located within a newly identified neural circuit regulating food intake—whose biology is distinct from both GLP-1 and amylin pathways.

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Novo Nordisk is exploring a direct listing on the New York Stock Exchange to replace current American depositary receipts and boost its US profile. CEO Mike Doustdar confirmed the potential move during an interview with the Financial Times.

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