FDA Grants Orphan Drug Designation to Novel Fascin Inhibitor NP-G2-044 for Pancreatic Cancer Treatment
核心洞察
The FDA has granted orphan drug designation to NP-G2-044 (Prilukae (搜索)), a novel oral fascin (搜索) inhibitor developed by Novita Pharmaceuticals (搜索) for treating pancreatic cancer (搜索) as monotherapy and in combination with anti-PD-1 immune checkpoint inhibitors.
Phase 1/2 clinical trial data showed a 21% objective response rate in 33 efficacy-evaluable patients receiving combination therapy, including 4 complete responses with 2 occurring in pancreatic cancer (搜索) patients.
The designation provides development incentives including tax credits, user fee exemptions, and potential 7-year market exclusivity, supporting advancement of this novel therapeutic approach targeting cancer metastasis and immune resistance.
The FDA has granted orphan drug designation (ODD) to NP-G2-044 (Prilukae (搜索)), a novel oral fascin (搜索) inhibitor developed by Novita Pharmaceuticals (搜索) for the treatment of pancreatic cancer (搜索). The designation covers both monotherapy use and combination therapy with anti-PD-1 immune checkpoint inhibitors, marking a significant regulatory milestone for this first-in-class therapeutic approach.
Pancreatic cancer (搜索) affects over 100,000 patients in the United States and remains among the deadliest malignancies, with a five-year survival rate of approximately 12%. The disease presents limited effective treatment options, particularly in advanced stages, with patients often facing treatment resistance and poor outcomes.
"FDA Orphan Drug Designation for our fascin (搜索) inhibitor represents an important regulatory milestone for Novita and validates the Company's scientific and clinical approach in the fight against pancreatic cancer (搜索), as it remains one of the most lethal solid tumors with limited therapeutic progress over decades," said Stewart Campbell, CEO of Novita Pharmaceuticals (搜索).
Novel Mechanism of Action
NP-G2-044 is a small molecule inhibitor designed to block tumor metastasis and enhance immune response by targeting fascin (搜索), the primary actin-bundling protein that plays a critical role in tumor cell migration and metastasis. By inhibiting fascin, the drug blocks the motility and invasion of tumor cells while simultaneously activating intratumoral dendritic cells, ultimately leading to the proliferation of CD8-positive T cells.
Cancer metastasis is the primary cause of over 90% of cancer-related deaths, yet there is currently no drug on the market specifically targeting metastasis. Additionally, while immune checkpoint inhibitors have made significant strides in cancer treatment, a large proportion of patients do not respond to existing immunotherapy treatments.
Preclinical evidence has demonstrated synergistic activity between NP-G2-044 and anti-PD-1 therapy (搜索), which enabled the conversion of nonresponsive tumors into responsive tumors. These findings served as the rationale for investigating NP-G2-044 as combination therapy in addition to monotherapy.
Clinical Trial Results
NP-G2-044 is currently under evaluation in the phase 1/2 NP-G2-044-P2-01 trial (NCT05023486), a multicenter, open-label study evaluating safety, tolerability, pharmacokinetics and pharmacodynamics, and preliminary antitumor activity in patients with advanced or metastatic solid tumors, including those with documented primary or acquired resistance to anti-PD-(L)1 therapy.
The trial includes patients with various malignancies alongside pancreatic ductal adenocarcinoma (搜索) (PDAC), including gynecologic cancers (搜索), triple-negative breast cancer (搜索), esophageal squamous cell carcinoma, cholangiocarcinoma, gastroesophageal junction adenocarcinoma, oropharyngeal squamous cell carcinoma, non-small cell lung cancer, and non-muscle invasive bladder cancer.
In the combination arm, NP-G2-044 is administered at 1600 mg or 2100 mg once daily along with previously initiated standard-of-care anti-PD-1 therapy (搜索). Data presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting showed durable responses among 33 efficacy-evaluable patients receiving combination therapy, with an objective response rate (ORR) of 21% (95% CI, 9%-38.9%).
This ORR included 4 complete responses, 2 of which were in patients with PDAC and gastroesophageal junction adenocarcinoma. The combination's safety profile was primarily characterized by diarrhea, fatigue, nausea, and transaminitis, which were transient and reversible. These promising efficacy data indicated the therapy's potential to overcome ICI resistance in PDAC and across multiple tumor types.
Regulatory Benefits and Future Development
Orphan Drug Designation is granted to investigational therapies intended to treat rare diseases affecting fewer than 200,000 patients in the United States. The designation provides development incentives, including eligibility for tax credits on qualified clinical trial costs, exemption from certain FDA user fees, and the potential for seven years of market exclusivity upon regulatory approval.
The FDA's designation was granted by the Office of Orphan Products Development (OOPD) and includes treatment of pancreatic cancer (搜索) in the setting of immune checkpoint inhibitor therapy. The study is ongoing and recruiting a total of approximately 140 adult patients across 18 locations in the United States.
The sponsor has indicated plans for more in-depth biomarker analyses to explore predictors of response and resistance, which will help guide personalized treatment strategies. Additionally, further development of NP-G2-044 in gynecologic cancers (搜索) has recently advanced into the pivotal phase 3 ULTIMUS-1 trial (NCT07109414), which is enrolling patients with platinum-resistant ovarian cancer (搜索).