With the development of chemotherapy agents, we've witnessed remarkable strides in the development of chemotherapy agents, resulting in improved efficacy and reduced side effects. However, a critical challenge persists that demands our attention: the management of chemotherapy-induced thrombocytopenia (CIT). Today, we'll explore a promising solution to this issue - Oprelvekin, a recombinant human interleukin-11 (IL-11).
Mechanism of Action
Oprelvekin's effectiveness lies in its ability to mimic the body's natural interleukin-11 (IL-11), a crucial thrombopoietic growth factor. When administered, Oprelvekin binds to IL-11 receptors, initiating a cascade of signal transduction events within the body. This pharmacological action stimulates the proliferation of hematopoietic stem cells (HCS) and megakaryocyte (MK) progenitor cells - the precursors to platelets. Furthermore, it promotes megakaryocyte maturation, ultimately leading to increased platelet production.
The Unmet Medical Needs: CIT
CIT represents a significant challenge in cancer treatment, often leading to disruptions in chemotherapy regimens and potentially compromising patient outcomes. This common complication can necessitate chemotherapy delays, dose reductions, or even treatment discontinuation, all while putting patients at increased risk for bleeding complications.
Despite its prevalence and clinical impact, CIT lacks a universally accepted definition. The most widely used criteria for grading CIT severity come from the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE). While the overall incidence of CIT varies depending on the specific chemotherapy regimen, clinically relevant thrombocytopenia requiring intervention occurs in approximately 5-10% of patients with solid tumors receiving cytotoxic chemotherapy. To provide context, the CTCAE (v5.0) grades 'Platelet count reduction' as follows:
- Grade 1: below the lower limit of the normal range down to 75*109/L
- Grade 2: 50~75 * 109/L
- Grade 3: 25~50 * 109/L
- Grade 4: less than 25 * 109/L
Taking the above definition, the incidence of CTCAE grade 3 or 4 CIT varies greatly from less than 2% to over 50% for common combination chemotherapy regimes.
Regimen
| Cancer | Incidence of Grade 3~4 CIT |
| Carboplatin | Various tumor types | 23% |
| Cisplatin | Carcinoma of unknow primary | 4% |
| Gemcitabine | Pancreas | 13% |
| Docetaxel | Breast | 2% |
| Temozolomide | Gliobastoma | 11% |
| Carboplatin/gemcitabine | Non-small cell lung | 56% |
| Carboplatin/pemetrexed | Non-small cell lung | 24% |
| Cisplain/gemcitabine | Carcinoma of unkown primary | 37% |
| Cisplain/pemetrexed | Non-small cell lung | 4% |
Historically, the U.S. FDA approved only one agent specifically for managing CIT: recombinant human IL-11 (Oprelvekin), marketed under the brand name Neumega by Wyeth Pharmaceuticals. However, Wyeth's discontinuation of Neumega has left a significant void in the global market for CIT treatment. Currently, there are no FDA-approved agents specifically designed to manage CIT, a situation mirrored in other major pharmaceutical markets worldwide.
This absence of specific therapies has forced healthcare providers to rely on suboptimal strategies:
Chemotherapy Adjustment - The standard of care now primarily involves reducing the relative-dose intensity of chemotherapy through:
- 1. Dose reductions;
- 2. Treatment delays;
- 3. Alterations to chemotherapy regiments.
Platelet transfusions - While an option, this approach has limited utility in patients with solid tumors and CIT due to:
- 1. High costs and dependent on blood donation;
- 2. Dependent on blood donation resulting in limited availability;
- 3. Short duration of effect;
The lact of a specific, FDA-approved treatment for CIT represents a significant unmet medical need in oncology. This gap not only impacts patient care but also presents a substantial opportunity for pharmaceutical innovation.
Market Opportunity
To address the unmet medical needs of CIT, Unibest presents a promising solution to address the critical unmet need in CIT management with an Oprelvekin product, which has been successfully commercialized in the Chinese market since 2008. The product is formulated as a small-volume lyophilized powder injection and is indicated to treat thrombocytopenia caused by radiotherapy and chemotherapy in cancer patients, with demonstrated significant advantages compared to both domestic and international products. The research achievement has reached international advanced standards. As an innovative drug with independent intellectual property rights, national invention patent, and National Class 1 New Drug Certificate, its successful launch filled a gap in the domestic market.
Our Oprelvekin's proven track record since 2008 positions it as a potentially valuable solution for the global CIT management landscape, particularly given the current void left by the discontinuation of Neumega in the U.S. market.
References
Al-Samkari, H. Thrombopoietin receptor agonists for chemotherapy-induced thrombocytopenia: a new solution for an old problem. Hematology Am Soc Hematol Educ Program 2022, 286–295 (2022).
Huang, M. et al. Interleukins in Platelet Biology: Unraveling the Complex Regulatory Network. Pharmaceuticals 17, 109 (2024).
Ciurea, S. O. & Hoffman, R. Cytokines for the Treatment of Thrombocytopenia. Seminars in Hematology 44, 166–182 (2007).
Al‐Samkari, H. & Soff, G. A. Clinical challenges and promising therapies for chemotherapy-induced thrombocytopenia. Expert Review of Hematology 14, 437–448 (2021).
