FDA Approves the First PROTAC in History, a $1B siRNA Wave Hits Cardiometabolic Disease, and Cytokinetics Cracks Non-Obstructive HCM – This Week in Biotech #99

Key Takeaways

• FDA approves Veppanu, first PROTAC protein degrader, for ESR1‑mutated breast cancer
• PROTAC approval creates regulatory pathway for targeted protein degradation therapies
• Madrigal licenses Arrowhead siRNA ARO‑PNPLA3 ($1B potential) for PNPLA3 I148M MASH
• GSK pays $1B for SiranBio ALK7 siRNA to cut visceral fat
• Cytokinetics’ aficamten meets primary and secondary endpoints in non‑obstructive HCM trial

Pulse Analysis

The clearance of Veppanu marks a watershed moment for the PROTAC platform, proving that the FDA will accept heterobifunctional degraders as a viable therapeutic class. By recruiting the cell’s ubiquitin‑proteasome system to eliminate disease‑causing proteins, PROTACs offer a mechanistic advantage over traditional inhibitors, especially for targets previously deemed “undruggable.” The modest progression‑free survival gain in the ESR1‑mutated cohort establishes a clinical foothold, while the biomarker‑restricted label sets a template for future precision‑focused launches.

At the same time, the rapid succession of multi‑hundred‑million siRNA deals underscores the maturation of RNA‑based therapeutics. Madrigal’s acquisition of Arrowhead’s PNPLA3‑targeting candidate leverages a clear genetic driver of fatty‑liver disease, delivering a 46% liver‑fat reduction in homozygous patients—a strikingly clean signal in a complex metabolic landscape. GSK’s $1 billion commitment to SiranBio’s ALK7 siRNA reflects a strategic push to complement GLP‑1 agents by preserving lean mass while trimming visceral adiposity. These transactions illustrate a broader industry shift toward genotype‑guided interventions that can be layered onto existing standard‑of‑care regimens.

Obesity and cardiometabolic disorders continue to dominate revenue growth, as evidenced by Novo Nordisk’s $355 million oral Wegovy sales in its first full quarter, far outpacing expectations. Meanwhile, Cytokinetics’ aficamten success in non‑obstructive hypertrophic cardiomyopathy fills a therapeutic void, delivering functional improvements despite a modest safety signal that will require echo monitoring. Together, these developments highlight a convergence of innovative modalities, robust commercial performance, and expanding indications that are reshaping the biotech investment landscape and accelerating the delivery of next‑generation medicines.