Disclaimer: Due to limited proficiency, errors are inevitable, and some information may not be the most up-to-date. Comments pointing out any issues are welcome. This article is only an introduction to medical and health-related drugs, not a recommendation of treatment plans (if involved); this article does not constitute any investment advice.
On August 16, 2024, the phase III clinical trial for the treatment of ischemic lower limb disease with resting pain using Northland's "Recombinant Human Hepatocyte Growth Factor Naked Plasmid Injection" (code name NL003) was unblinded according to the established plan, with primary endpoints meeting expectations. Preliminary results indicate: the primary endpoint, 180-day complete pain disappearance rate, showed that the NL003 group was significantly superior to the placebo control group (p<0.0001); the product demonstrated good safety, with no serious adverse reactions related to the drug observed.
Lower extremity ischemic disease is a common clinical condition, usually caused by arteriosclerosis obliterans (ASO), diabetic arteriosclerosis obliterans (DAO), and thromboangiitis obliterans (TAO), which lead to lower extremity arterial stenosis or occlusion and insufficient blood perfusion. This results in symptoms such as intermittent claudication, pain, ulcers, or gangrene in the lower limbs. Based on the severity of ischemia, the Rutherford classification is clinically used to categorize lower extremity ischemic diseases from mild to severe into grades 0-6. Grades 4-6 are considered critical limb ischemia (CLI), with main clinical manifestations including rest pain in the legs and feet, ulcers, and gangrene. As the disease progresses, infections, ulcers, and gangrene worsen, potentially leading to amputation or even death in severe cases. NL003 Phase III Clinical Trial Mainly Targets CLI, divided into two indications: ulcer (Rutherford grade 5) and rest pain (Rutherford grade 4), with trials conducted separately. The trial adopted a randomized, double-blind, placebo, parallel control research mechanism, led by the Vascular Surgery Department of Peking Union Medical College Hospital, with clinical research carried out in 24 hospitals across China. Among them, 242 cases were enrolled for the ulcer indication and 302 cases for the rest pain trial. The ulcer indication completed the trial first in February 2024 and officially received acceptance for a New Drug Application (NDA) from the CDE in July.China's First NDA Application for a Plasmid DNA Gene Therapy DrugAfter the unblinding of the resting pain indication this time, a comprehensive and in-depth analysis must be carried out according to the regulations of the protocol and statistical analysis plan, and the clinical trial summary report must be completed. The company is simultaneously working on drafting the application materials for the new drug marketing authorization for this indication and will actively communicate with the pharmaceutical regulatory authorities regarding the submission matters.Plan to submit a Biologics License Application within this year（BLA）。Currently, there are no effective therapeutic drugs for CLI worldwide. Clinical treatments mainly rely on surgical methods such as interventional procedures and vascular bypass, which have limited means and unsatisfactory treatment outcomes. NL003 is an innovative gene therapy drug that uses a plasmid vector. By locally injecting NL003 into the ischemic muscle area, the plasmid transfects striated muscle cells and continuously expresses and secretes the hepatocyte growth factor (HGF) protein, which promotes blood vessel growth. This stimulates new blood vessel regeneration in the ischemic area, forming collateral circulation and establishing a "molecular bypass" mechanism to increase blood flow supply to the ischemic region, thereby achieving therapeutic effects. Compared with traditional vascular reconstruction surgeries, NL003 has significant advantages in terms of invasiveness, operational convenience, patient compliance, efficacy, and durability, offering patients sustained clinical benefits.According to the "2022 Report on Cardiovascular Health and Diseases in China," the prevalence of lower extremity PAD (peripheral artery disease) in the general population aged 35 and above in China is 6.6%, with approximately 45.3 million cases. About 10% of patients with lower extremity PAD will progress to CLI (critical limb ischemia), which is characterized by a high incidence, long disease course, and high disability rate. The 5-year mortality rate exceeds 50%, significantly higher than most severe diseases, including many cancers. With the development of China’s socio-economy and improvements in healthcare, life expectancy has increased, the elderly population continues to grow, and the aging process is accelerating. In the future, the number of PAD patients is expected to keep rising, indicating significant unmet medical needs.The biopharmaceutical industry is one of China's strategic pillar industries. Recently, Beijing, Shanghai, and other regions have issued the "Several Opinions on Supporting the Whole-Chain Innovation and Development of the Biomedical Industry," increasing support for the research and development of innovative drugs and medical devices, and proactively laying out cutting-edge fields such as gene and cell therapy, mRNA, and more. Gene therapy drugs have become one of the key areas that major pharmaceutical companies are rushing to develop. Northland has been dedicated to the development of gene therapy drugs for 20 years, establishing a mature technology platform. NL003, the first plasmid-based gene therapy drug submitted by our company for an NDA application, has a leading R&D progress in China. To achieve the company’s strategic transformation from a Biotech to a Biopharm, Northland is constructing a bioengineering drug production base. The three main buildings—comprehensive office building, production workshop, and intelligent warehouse—were topped off in 2023, and the production workshop will be ready for bulk drug substance production by the end of this year. The company has also partnered with the internationally renowned pharmaceutical consulting firm IQVIA to actively prepare for the commercialization of NL003. We look forward to NL003 being approved for marketing soon, becoming the world’s first truly plasmid-based gene therapy drug, providing a new treatment option for patients with lower limb ischemic diseases.
Source of the article: Company's official website
