The key to cancer treatment in the new era: Interpretation of the opportunities and clinical practice of pemetinib/pemetinib in the Chinese market

In the treatment of advanced cholangiocarcinoma (CCA) and some rare myeloid/lymphoid tumors, there has long been a lack of specific targeted drugs. With the development of precision medicine, more and more tumor types are identified through genetic abnormalities and can be "hit" with specially designed small molecule drugs. Pemigatinib (trade name Pemazyre/Dabotan) is an oral inhibitor that targets FGFR (fibroblast growth factor receptor) fusion/rearrangement. The drug has been approved in many regions around the world and is entering the Chinese market, bringing new treatment hope.

1. From laboratory to clinic: pemetinib’s development milestones and global approval path

Pemetinib is the world’s first targeted therapy targetingFGFR2 fusion/rearrangement. In April 2020, the U.S. FDA approved it for the second-line treatment of FGFR2 fusion-positive cholangiocarcinoma based on the FIGHT-202 trial data, creating the first targeted therapy for FGFR-driven tumors. In March 2022, China's NMPA followed suit and approved pemetinib for patients with previously treated unresectable or metastatic cholangiocarcinoma, marking China as the second country in the world to have this indication. In August of the same year, the FDA further expanded its indications to patients with relapsed/refractory myeloid/lymphoid neoplasms (MLN) with FGFR1 rearrangements, highlighting the potential of the drug in the field of hematological tumors.

Clinical data support:

In the FIGHT-202 trial, 146 patients with FGFR2 fusion-positive cholangiocarcinoma received treatment, with an objective response rate (ORR) of 35.5%, a median progression-free survival (PFS) of 6.9 months, and a median overall survival (OS) of 21.1 months, which were better than traditional chemotherapy regimens (PFS 2.1 months, OS 7.7 months).

The FIGHT-203 trial showed that 70% of MLN patients in the chronic phase achieved complete remission (CR), 16 of them maintained a cancer-free state for more than 1 year, and 5 of them survived long-term after completing stem cell transplantation.

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2. Expansion of indications: Breakthrough in the treatment boundary from cholangiocarcinoma to pan-cancer types

1. Cholangiocarcinoma: a revolutionary choice for second-line treatment

Cholangiocarcinoma is a highly common tumor in Asia, and approximately 10%-15% of patients have FGFR2 fusion/rearrangement. The approval of pemetinib fills the gap in second-line treatment, especially for patients who fail gemcitabine + cisplatin chemotherapy. In clinical practice, patients need to confirm the FGFR2 mutation status through companion diagnostics (such as the detection reagents cooperated by Innovent Biologics and Genega) before starting treatment.

Optimization of medication regimen:

The standard dose is13.5 mg once daily for 14 consecutive days with 7 days off (21-day cycle).

Patients with hepatic insufficiency need to reduce the dose to 9mg. Elderly patients (>65 years old) do not need to adjust the dose.

2. Myeloid/Lymphoid Tumors: Survival Breakthrough for Refractory Cases

MLN with FGFR1 rearrangement is a rare and aggressive hematological tumor with a median survival of less than 1 year. By inhibiting the FGFR1 signaling pathway, pemetinib enabled 70% of patients in the chronic phase to achieve CR. Among them, 22 of 23 patients maintained remission for more than 6 months, and 5 patients survived long-term after completing stem cell transplantation. The CR rate for patients in the acute phase reached 44%, providing transplant opportunities for high-risk groups.

3. Pan-cancer species exploration: Basket experiments reveal new potential

Data from the FIGHT-207 trial released by AACR in 2023 show that pemetinib exhibits cross-cancer efficacy in solid tumors with FGFR mutations:

FGFR fusion/rearrangement cohort (n=49): ORR 26.5%, DCR 65.3%, median PFS 4.5 months.

FGFR point mutation cohort (n=32): ORR 9.4%, DCR 56.3%, suggesting the need for precise screening of biomarkers.

In cancer types such as urothelial carcinoma and glioblastoma, Partial responses have also been observed in patients with FGFR2/3 mutations.

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3. Adverse reaction management: High phosphorus and eye toxicity are core risks

Two types of toxicity require the most attention in clinical practice:

1. Hyperphosphatemia:Because FGFR inhibition is related to phosphorus metabolism, which may lead to elevated blood phosphate and secondary soft tissue calcification. Measure baseline blood phosphorus and calcium before treatment, monitor periodically during treatment, use phosphorus binders and adjust diet (reduce high-phosphorus foods) if necessary. In severe cases, dose reduction or suspension of medication is required.

2. Retina/macular changes (including retinal pigment epithelial detachment, etc.): Pemetinib can cause visual symptoms. Before treatment, an ophthalmological OCT baseline examination should be performed, followed by frequent reexaminations and patients should be reminded to seek medical attention immediately if they experience blurred vision or floaters. If confirmed ocular toxicity is discovered, the drug must be discontinued promptly and the ophthalmology department must decide on a recovery or dressing strategy.

In addition, you need to pay attention to common adverse reactions such as skin/nail changes, hair loss, digestive tract symptoms, fatigue, etc., and actively ask and record them during outpatient follow-up. The systematic review also provides a comprehensive evaluation of the safety spectrum, emphasizing the importance of early detection and multidisciplinary management.

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IV. Global Market Structure: Competition and Selection of Original Drugs and Generic Drugs

1. Price system: the leap from sky-high prices to inclusive benefits

Chinese original drug: Available domestically in two specifications: 4.5 mg×14 tablets and 9 mg×14 tablets, with a retail price of approximately RMB 20,000-50,000 per box.

Overseas original drug:13.5mg × 14 tablets is about 70,000 yuan (in the United States), which is affected by exchange rate fluctuations.

Although the domestic price is relatively low, if the treatment cycle is long and the dosage is adjusted frequently, the overall treatment cost is still high. In addition, the lack of coverage by medical insurance means that most patients need to pay out of pocket or rely on commercial insurance/assistance projects; FGFR2 fusion/rearrangement needs to be tested before use , and the testing costs and procedures also require additional burdens.

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Overseas generic drugs: Laos Lucius Pharmaceuticals4.5mg

2. Drug purchase channels: compliance and risk control

Domestic hospitals/DTP pharmacies: Drug fidelity and cold chain distribution are supported, but the pressure is high to pay for them all out of pocket.

Formal cross-border purchasing platform: Directly mailed to your home, with traceability code provided. Be wary of low-price traps (poor packaging or fake without code).

Overseas direct purchase: Laos/Indian pharmacies have extremely low prices, but they need to bear language, transportation costs and the risk of counterfeit drugs.

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5. Patient perspective and medical practice suggestions

1. How to select patients suitable for pemetinib?

It is clear that the patient is a cholangiocarcinoma patient who has failed previous treatment (such as progression after chemotherapy) or is unresectable/metastasized.

Must be tested positive for FGFR2 fusion or rearrangement (or FGFR1 rearrangement for corresponding indications). The test must be reliable and it is recommended to use a validated NGS/clinical companion diagnostic platform.

Before starting treatment, conduct baseline examinations: blood phosphorus, kidney and liver function, vision and fundus/OCT, bone metabolism indicators, thyroid, electrocardiogram, etc.

Fully communicate with patients: the drug is precisely targeted, but not suitable for everyone; it has potential serious toxicity (high phosphorus, retinal toxicity); the cost is still high; long-term treatment may be required.

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2. Key points of medical management during the treatment process

Regular monitoring: weekly blood phosphorus, calcium, kidney and liver function, bone alkaline phosphatase, visual nerve function, ophthalmology OCT is recommended every 2 months/3 months.

Educate patients to avoid phosphorus-rich diets, conduct regular follow-up visits, and report blurred vision/eye pain/new abdominal pain/infection symptoms early.

If high phosphorus occurs, phosphorus binding agents (such as calcium carbonate, colloids) should be used promptly and dosage reduction or temporary discontinuation should be considered.

If vision is abnormal, medication must be suspended immediately and ophthalmology evaluation must be performed. If RPED is confirmed, the drug should be discontinued and the treatment plan should be adjusted.

Discuss treatment goals with patient: This drug may improve response rate or prolong response duration, but is not guaranteed"Cure". The efficacy and drug resistance need to be closely observed.

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3. Patient financial and psychological support

Medical staff, social workers and patient organizations should discuss economic options together: whether there is commercial insurance coverage, high-end medical insurance, self-pay ratio, whether there is a patient assistance plan, whether to consider international purchase of drugs or generic drugs (but pay attention to legality and safety).

Psychological support is equally important: For patients with advanced cancer, choosing high-priced targeted therapy may bring hope and anxiety at the same time. Patients should be helped to make reasonable expectations and develop treatment, monitoring and exit strategies.

References:

1. FDA news release — FDA grants accelerated approval to pemigatinib for cholangiocarcinoma with an FGFR2 rearrangement or fusion. U.S. Food & Drug Administration.

2. Pemazyre (Pemigatinib) prescribing information/label (accessdata.fda.gov PDF).

3. FIGHT-202 final results / Lancet/Annals of Oncology publications (pemigatinib in cholangiocarcinoma).

4. Incyte press release — FDA approvals and indications for Pemazyre.

Incyte Investor

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