Amgen Exits CNS Drug Development and Partners with BeiGene: The End of the Blockbuster Drug Model

Drug Source News

Yesterday, Amgen announced its exit from central nervous system (CNS) drug development and a layoff of 180 employees, while stating that it would continue to participate in new drug discovery in this field through other models. Today, Amgen announced that it will acquire a 20.5% stake in BeiGene for $175 per share, with a total value of $2.7 billion. BeiGene will contribute $1.25 billion and 600 researchers to assist in the development of approximately 20 drugs under investigation by Amgen, including AMG510, and will receive certain commercial rights. Additionally, BeiGene will establish a sales team of 700 people to market three of Amgen’s cancer drugs—Xgeva, Kyprolis, and Blincyto—in the Chinese market.

Drug Source Analysis

There was a time when the pharmaceutical industry relied heavily on so-called blockbuster drugs, superficially defined as those with annual sales exceeding $1 billion. However, two decades ago, only widely used medications for common diseases could achieve such sales performance. At that time, many criticized the pharmaceutical industry for focusing excessively on these high-profit mass-market drugs while neglecting rare diseases that suffered from a severe lack of medical treatments and resources. Central nervous system (CNS) disorders constituted a major component of the blockbuster drug portfolio. Over the past decade, Amgen’s $400 million acquisition of the Icelandic genetics company deCODE and its $1.55 billion acquisition of Dezima, a developer of CETP inhibitors, were both aimed at achieving breakthroughs in the field of common disease medications. Nevertheless, with changes in new drug discovery technologies, clinical development, and the reimbursement landscape, the traditional blockbuster model is indeed facing numerous challenges.

Amgen’s own experience reflects this reality. Leaving aside its failed BACE inhibitors, even PCSK9 inhibitor Repatha and migraine drug Aimovig—both of which were virtually flawless from target discovery through clinical development—have faced stringent controls by payers, despite numerous large and small clinical trials that were almost uniformly positive. In contrast, the early clinical data from just 10 patients treated with AMG510, a G12C inhibitor targeting only 10% of KRAS mutations, spurred a $3 billion increase in market capitalization in a single day. This stark contrast offers profound insights into investment directions. While favorable reimbursement policies are undoubtedly the primary driver, the approval of many oncology drugs via the Accelerated Approval (AA) pathway based on early response rate data is also a significant factor. Furthermore, preclinical development of oncology drugs follows relatively clear pathways, aligning well with the current mainstream target-centric R&D model.

Central nervous system (CNS) drugs differ markedly from oncology drugs in these key determinants. In addition to significant payer resistance and limited shortcuts in clinical development, few single-gene variants can be causally linked to common CNS disorders; it is estimated that sample sizes exceeding tens of thousands are required to identify any reliable CNS disease-causing genes. The human brain is both exceedingly complex and remarkably simple. Its complexity lies in the fact that half of the human genome is expressed exclusively in the brain, and neural network functions are so intricate that they represent the ultimate goal of artificial intelligence. Its simplicity is reflected in the fact that even the most brilliant minds in the industry appear simplistic when confronted with such a complex system. Not only Amgen, but many other large pharmaceutical companies have exited the CNS space; those that remain, such as Biogen, face severe challenges. Of course, new drugs do not necessarily have to be discovered following mainstream paradigms; at times, we need to step out of our comfort zone. Based on the association between fluctuations in allopregnanolone levels around parturition and depression, Sage Therapeutics developed Zulresso and successfully designed an oral analog, Zuranolone, which demonstrated efficacy in Phase II trials for major depressive disorder.

Oncology remains one of the areas with the greatest unmet medical needs. Years of intensive investment in basic research have led to significant advances in tumor biology, and the rise of cancer immunotherapy has enabled the translation of numerous immunological achievements into the oncology field. However, concerns about excessive investment in oncology persist; for instance, the R&D Director of Novartis, a pharmaceutical giant in oncology, publicly raised this issue last year. The severity of central nervous system (CNS) disorders is often underestimated. A recent survey of patients with comorbid depression and asthma found that 93% would prioritize treating their depression if they could only receive treatment for one condition. The CEO of Sage Therapeutics stated that criticisms regarding the inconvenience of Zulresso’s 60-hour infusion regimen reflect an underestimation of the severity of postpartum depression. Investment in new drugs does not always align with disease burden, and Amgen’s recent actions indicate that the traditional blockbuster drug model is essentially obsolete.