Hyperway Pharma's HBW-004285 Shows Promise, Potentially Surpassing VX-548 in Clinical Trials

Hyperway Pharma, officially known as Chengdu Hyperway Pharmaceuticals Co., Ltd., has recently completed the phase I clinical study of their independently developed Nav1.8 inhibitor, HBW-004285. The clinical data indicate that, when compared to VX-548（Journavx）—the first Nav1.8 inhibitor to reach the market—HBW-004285 boasts a higher safety profile with no adverse reactions above Grade 1. Additionally, HBW-004285 demonstrates a faster onset of action, superior pharmacokinetic characteristics, and no gender differences, positioning it as a strong contender to surpass VX-548 and become a Best-In-Class medicine.

Figure 1: HBW-004285 Tablet V.S. Vertex Compounds

Nav1.8 is a voltage-gated sodium channel primarily expressed in sensory neurons of the peripheral nervous system. It plays a key role in transmitting pain signals without causing opioid-like addiction, making it highly sought after as a pivotal target in analgesic drug development.

VX-548 (Journavx), developed by Vertex Pharmaceuticals, is the first Nav1.8 inhibitor approved by the U.S. Food and Drug Administration (FDA) on January 30, 2025. VX-548 is also the first non-addictive drug for acute pain treatment introduced in over 20 years—a landmark achievement. Vertex's clinical success with VX-548 led to a 13% surge in their stock price in a single day, pushing their market value past $100 billion. Leerink Partners analysts predict that by 2030, annual sales of VX-548 could reach $5.1 billion, underscoring the significant market potential and clinical importance of VX-548 and other Nav1.8 inhibitors.

Figure 2: HBW-004285 PK Curves and Safety Ratios

HBW-004285 is a pivotal analgesic drug in Hyperway Pharma’s pipeline. When compared to VX-548, HBW-004285 has showcased exceptional advantages in preclinical head-to-head comparisons, such as a superior pharmacokinetic profile, faster and longer-lasting analgesic effects, and higher safety. These preclinical benefits have been validated in the phase I clinical trials.

Higher Safety: None of the subjects experienced adverse reactions above Grade 1. Only some subjects had Grade 1 adverse reactions (including some subjects in the placebo group) and showed no dose dependence. Additionally, a reported 28-day GLP toxicity test in monkeys showed that VX-548 had safety ratios of 2.8 (AUC(0-t)) and 3.8 (Cmax) at the clinically efficacious dose, suggesting a narrow safety window. Conversely, a 28-day GLP toxicology study in dogs revealed that HBW-004285 tablets had safety ratios more than 10 times higher, indicating significantly better clinical safety compared to VX-548.

Faster Onset of Action: Phase I clinical studies demonstrated that HBW-004285 tablets reached Tmax at 1.5-2 hours post-administration. Rapid onset of pain relief is especially critical for both acute and chronic pain management. In comparison, the average human Tmax of VX-548 is 6 hours, with its active metabolite reaching Tmax at 12 hours according to phase II clinical results.

Superior Pharmacokinetic Characteristics: HBW-004285 tablets exhibited excellent clinical dose linearity, with no accumulation tendency and no significant gender differences. In the MAD (Multiple Ascending Dose) study, the exposure (AUC) of HBW-004285 tablets at Dose 2 was approximately twice that of Dose 1, and at Dose 3, it was 1.5 times that of Dose 2. The exposure on the 7th day was 1.25-1.37 times that of the first day, indicating no accumulation tendency.

Promising Analgesic Trends: Preliminary data suggest that HBW-004285 may have a superior analgesic effect compared to VX-548. Blood concentrations of HBW-004285 at all dose groups exceeded Adjusted IC90 levels (converted according to the free drug concentration). Based on current clinical data, it is anticipated that HBW-004285 tablets can produce significant analgesic effects at Dose 2. Additionally, Figure 3 analysis indicates that HBW-004285 may offer more effective analgesia than VX-548 in humans based on Cmax/Adjusted IC50 or IC90 value analysis.

Figure 3:  The Comparison of Drug Concentrations in Human Blood with Adjusted IC50 and Adjusted IC90

Overall, Hyperway Pharma's Nav1.8 inhibitor, HBW-004285 tablets, have demonstrated good safety, tolerability, pharmacokinetic characteristics, and preliminary analgesic effects in phase I clinical studies. With the potential to surpass VX-548 and become a Best-In-Class medicine, HBW-004285 shows significant market development prospects. Hyperway Pharma is committed to rapidly advancing the research and development of the HBW-004285 project and is expected to complete the phase II clinical study and initiate the phase III clinical study in 2025.

About Hyperway Pharma

Hyperway Pharma is a rapidly growing biotech company dedicated to developing best-in-class and first-in-class drugs to address unmet medical needs. Their world-class R&D team, composed of experts across various disciplines, focuses on driving original innovation throughout the entire drug research and development process. Prioritizing speed and quality, Hyperway Pharma has developed a robust pipeline of over ten innovative drugs targeting oncology and pain. Their specialized platform for developing brain-penetrating drugs highlights their insights and expertise in drug discovery. With an extensive intellectual property portfolio comprising over 30 patent applications and 20 authorizations, Hyperway Pharma underscores its commitment to cutting-edge science. Furthermore, their success in rapidly moving preclinical drug candidates into clinical trials showcases their ability to execute effectively. The selection of their research for presentation at renowned conferences such as ASCO, AACR, and EHA further validates their industry competitiveness.

By investing more in research and development and forming collaborative partnerships, Hyperway Pharma aims to expedite the development of new drugs and expand its market presence in China. Through strategic collaborations, including regional rights transfers, technical collaboration, or technology licensing, Hyperway Pharma seeks to partner with external organizations to develop valuable drugs that meet the needs of the Chinese market in terms of quality and affordability.