Pamiparib is a targeted therapy drug used to treat certain cancers, particularly those with defects in their DNA repair machinery. This medication belongs to the class of Poly(ADP-ribose) polymerase (PARP) inhibitors. Administered orally, pamiparib interferes with the cancer cell’s ability to fix DNA damage, leading to the selective death of malignant cells.
How Pamiparib Targets Cancer Cells
Pamiparib is a potent and selective inhibitor of the PARP enzymes, specifically PARP1 and PARP2. Normally, PARP enzymes detect and initiate the repair of single-strand DNA breaks (SSBs) through the Base Excision Repair pathway. By blocking PARP1 and PARP2 activity, pamiparib prevents the repair of these minor DNA lesions, causing them to accumulate.
When the cancer cell attempts DNA replication, the unrepaired SSBs are converted into double-strand DNA breaks (DSBs). Normal cells rely on the Homologous Recombination (HR) pathway to repair DSBs. However, cancer cells sensitive to pamiparib have a pre-existing fault in their HR pathway, often due to mutations in genes such as BRCA1 or BRCA2.
This therapeutic strategy is based on the concept of “synthetic lethality,” where the simultaneous failure of two non-essential cellular processes results in cell death. The two compromised processes are the HR pathway (due to the BRCA mutation) and the PARP-mediated repair pathway (blocked by pamiparib). Since normal, healthy cells retain a functional HR pathway, they can effectively repair the DSBs caused by PARP inhibition, which allows pamiparib to selectively destroy the cancer cells while sparing most healthy tissue. Pamiparib also causes PARP trapping, locking the enzyme onto the DNA damage site, which physically obstructs DNA replication and repair.
Clinical Applications and Indications
Pamiparib (trade names Baihuize or PARTRUVIX) has received regulatory approval in China for gynecologic malignancies. It is indicated for patients with recurrent advanced ovarian, fallopian tube, or primary peritoneal cancer. This approval applies specifically to patients whose tumors have a germline BRCA mutation and who have been previously treated with two or more lines of chemotherapy.
The drug is actively investigated in clinical trials for other tumor types that harbor similar DNA repair deficiencies. These investigations include studies in breast cancer, particularly the triple-negative and HER2-negative subtypes that frequently show BRCA mutations. Other solid tumors under evaluation include metastatic castration-resistant prostate cancer and small cell lung cancer.
Pamiparib is explored as both a monotherapy and in combination with other anti-cancer agents, such as chemotherapy or immunotherapy. It is also being examined as maintenance therapy following initial chemotherapy in patients with platinum-sensitive recurrent ovarian cancer. Its ability to penetrate the blood-brain barrier supports investigation in central nervous system tumors, such as glioblastoma.
Understanding the Safety Profile
The safety profile of pamiparib, similar to other PARP inhibitors, is characterized by side effects related to its effect on rapidly dividing cells, such as those in the bone marrow and gastrointestinal tract. The most frequently reported adverse events are hematologic. These include:
- Anemia (low red blood cell count)
- Neutropenia (low neutrophil count)
- Leukopenia (low white blood cell count)
- Thrombocytopenia (low platelet count)
Anemia often causes symptoms such as fatigue, weakness, and shortness of breath. Neutropenia and leukopenia increase the risk of infection, while thrombocytopenia raises the risk of bruising and bleeding. Severe blood disorders, classified as Grade 3 or higher, are common and may require dose interruption, reduction, or supportive care like blood transfusions.
Gastrointestinal issues are also common, including nausea, vomiting, decreased appetite, and diarrhea. Fatigue is frequently reported and can significantly impact a patient’s quality of life. Less frequently, patients may experience elevated liver enzymes, which requires regular monitoring of liver function tests.
In rare instances, pamiparib carries a risk of secondary Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML). These blood cancers can occur months to years after starting treatment, with a median latency period typically ranging from 18 to 27 months for the class. Although the overall incidence of MDS and AML associated with the PARP inhibitor class is low, close and continued monitoring of blood counts is performed throughout the treatment course.
Global Regulatory Status
Pamiparib was approved by the National Medical Products Administration (NMPA) in China in 2021. This conditional approval covers recurrent ovarian, fallopian tube, or primary peritoneal cancers with a germline BRCA mutation. Global approval in other major markets is pending the results of ongoing clinical trials.
In the United States and the European Union, pamiparib remains an investigational drug, lacking marketing authorization from the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA). The manufacturer is conducting late-stage clinical trials to generate the necessary efficacy and safety data for future submissions to these international regulatory bodies.