The late-stage trial of the Duchenne gene therapy suffered a setback. Leading precision gene therapy company Sarepta (SRPT.US) saw its stock plunge more than 39% in after-hours trading.

After the late-stage clinical trials of two gene therapies for Duchenne muscular dystrophy (DMD), AMONDYS 45 (casimersen) and VYONDYS 53 (golodirsen), failed to reach their main goals, the stock price of Sarepta Therapeutics (SRPT.US), a globally renowned biotechnology company specializing in rare disease therapies, plummeted by over 39% in after-hours trading on the US stock market. It is understood that this clinical trial included a group of 225 boys aged between 6 and 13 years old, who have a specific Duchenne mutation that can be addressed by skipping exon 45 or 53. The biotechnology company stated that this nine-year study faced significant challenges due to the COVID-19 pandemic, which severely affected the trial participants and overall trial results. In terms of safety, the company's overall research presented good and stable safety features observed over the years in exon-skipping therapies. Sarepta also reported a slight decrease in revenue in the third quarter of about 14.5%, totaling $399 million, but exceeding Wall Street analysts' expectations by $62.37 million. Sarepta Therapeutics is a biotechnology company headquartered in Cambridge, Massachusetts, USA, with a focus on precision genetic medicine. Its core business area is rare genetic muscle diseases, particularly Duchenne muscular dystrophy (DMD) and some forms of limb-girdle muscular dystrophy (LGMD). Sarepta's commercial products and research pipeline mainly revolve around DMD/muscular dystrophy. The two main technological routes are RNA exon skipping therapy, using technologies like PMO oligonucleotides to skip mutated exons of the DMD gene and restore a truncated version of the dystrophin protein; and gene therapy (AAV vectors), represented by Elevidys, the first FDA approved gene therapy product for Duchenne muscular dystrophy, but this line has faced significant safety and regulatory pressures in the past year (multiple cases of liver function failure deaths, FDA requested halt in shipping/clinical trials, etc.). The sharp drop in Sarepta's stock price after hours is primarily due to the critical failure of the phase 3 clinical trials and the sharp increase in pipeline uncertainty, rather than just financial data fluctuations. The late-stage phase 3 ESSENCE clinical trials of the two exon skipping drugs AMONDYS 45 and VYONDYS 53 did not reach statistical significance on the main endpoints, casting greater uncertainty over future full approval, pricing, and sales. Against the backdrop of ongoing safety and regulatory pressures, this triggered a market "stampede" sell-off. Despite setbacks, Sarepta stated that it still plans to meet with officials from the US Food and Drug Administration (FDA) to discuss transitioning the current accelerated approval of these drugs to full approval. Duchenne muscular dystrophy typically begins in early childhood and worsens over time, making walking, breathing, and other daily activities increasingly difficult. Due to increased regulatory scrutiny in recent years and the deaths of three patients related to the company's other gene therapy Elevidys, leading to a temporary halt in clinical trials and concerns about the company's safety oversight, Sarepta's market value has dropped by approximately 80% this year, leading to a significant decline in its stock price.