Breaking New Ground in 2025 with 8 First-in-Class Drugs Close to FDA Approval – Part II

Building on the progress of 2024, the FDA will approve additional first-in-class drugs in 2025, potentially revolutionizing treatment options. These upcoming therapies, which include novel biologics and small molecules, are targeting a broad range of conditions, from rare diseases to more common ailments that continue to present significant challenges. With new mechanisms of action, these drugs offer fresh approaches to treating conditions with limited or no current therapeutic options. Below are 4 more promising candidates set to make a significant impact on the pharmaceutical landscape in 2025.

UGN-102 Combines Mitomycin with Reverse Thermal Gel Technology for Non-Surgical Bladder Cancer Treatment

UGN-102 combines the chemotherapeutic agent mitomycin with UroGen’s proprietary reverse thermal gel technology. Administered directly into the bladder as a liquid at lower temperatures, it transforms into a gel upon reaching body temperature. This gel-like formulation allows mitomycin to remain in prolonged contact with the bladder lining, enhancing its ability to effectively ablate cancerous cells. 

UGN-102 offers a non-surgical treatment alternative to the current standard of care for low-grade, intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC). This typically involves transurethral resection of bladder tumor (TURBT). In phase 3 trials, UGN-102 showed a complete response rate of 79.6% three months after the initial treatment, with 82.3% of patients maintaining this response at 12 months. The drug also demonstrated a 55% reduction in the risk of recurrence, progression, or death when compared to TURBT alone. 

Plozasiran for Severe Hypertriglyceridemia and Familial Chylomicronemia Syndrome Targets Elevated Triglycerides

Arrowhead’s first-in-class drug candidate, plozasiran, is under development for both severe hypertriglyceridemia (SHTG) and familial chylomicronemia syndrome (FCS), with a potential market launch in 2025. SHTG causes dangerously high triglyceride levels in the blood, while FCS results from a genetic disorder that leads to severe triglyceride elevation due to chylomicron accumulation. Elevated triglycerides can lead to serious health complications, including pancreatitis and cardiovascular diseases.

Plozasiran is an RNA interference (RNAi) therapeutic that targets the production of apolipoprotein C-III (APOC3), a key regulator of triglyceride metabolism. By silencing the mRNA of the APOC3 gene in liver cells, plozasiran reduces the synthesis of APOC3, resulting in decreased triglyceride-rich lipoproteins in the bloodstream. Clinical studies have shown that plozasiran significantly lowers triglyceride levels, with most participants achieving levels below the 500 mg/dL threshold that signifies acute pancreatitis risk. The drug also improved other triglyceride-related lipoprotein parameters.

UX111 Gene Therapy for Sanfilippo Syndrome Type A Reduces Heparan Sulfate Levels

UX111 is a gene therapy designed to treat Sanfilippo Syndrome type A (MPS 3A) by delivering a functional copy of the SGSH gene, which encodes the heparan N-sulfatase enzyme, directly to the central nervous system (CNS). The therapy uses an AAV vector and administers through a single intravenous infusion. Once delivered, the functional gene enables the production of the enzyme that is deficient in patients, allowing the breakdown of accumulated heparan sulfate. Clinical studies have shown a reduction in cerebrospinal fluid heparan sulfate levels, which serves as a biomarker for disease activity. Preliminary data also suggest that UX111 may help stabilize or improve neurocognitive function in treated patients.

Sanfilippo Syndrome type A (MPS 3A) results from a deficiency in the enzyme heparan N-sulfatase, making it a rare genetic disorder. This enzyme deficiency leads to the buildup of heparan sulfate, which primarily affects the CNS and results in progressive neurodegeneration. The condition typically manifests in childhood, with affected individuals experiencing developmental delays, cognitive decline, motor dysfunction, sleep disturbances, and behavioral issues. Over time, the disease severely impacts quality of life, and patients often face a shortened lifespan.

Currently, no treatments exist to address the underlying cause of Sanfilippo Syndrome type A. UX111 presents a promising therapeutic option by directly targeting the root cause of the disease. Ultragenyx Pharmaceuticals plans to seek accelerated approval for the therapy. The FDA has agreed to consider cerebrospinal fluid heparan sulfate levels as a surrogate endpoint for efficacy, and Ultragenyx submitted its Biologics License Application (BLA) in December 2024. 

Telisotuzumab Vedotin Targets c-Met Overexpression in Cancer

Telisotuzumab vedotin, developed by Abbvie, is an antibody-drug conjugate (ADC) designed to target cancers that overexpress the c-Met protein. c-Met is a receptor tyrosine kinase involved in crucial cellular functions such as growth, survival, and metastasis. C-Met overexpression drives tumor progression and worsens prognosis in various cancers, including non-small cell lung cancer (NSCLC).

Telisotuzumab vedotin uses a monoclonal antibody to bind specifically to the c-Met protein on the surface of cancer cells and releases the cytotoxic agent, monomethyl auristatin E (MMAE), inside the cell to induce cell cycle arrest and programmed cell death. Currently, there are no approved therapies specifically targeting c-Met overexpression in NSCLC. By delivering a potent cytotoxic agent directly to c-Met–expressing tumor cells, this drug aims to enhance treatment efficacy while minimizing damage to normal tissues.

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Denisse Sandoval