Analysis of the real efficacy and side effects of Adagrasib in KRAS mutated non-small cell lung cancer, and price purchase channels at home and abroad
1. Hot topics: KRAS The "hard bones" of mutation finally ushered in a new breakthrough
For a long time, KRAS mutations were considered “undruggable” gene mutations. Especially in non-small cell lung cancer (NSCLC), about 13% of patients carry KRAS G12C mutations. Such patients often respond poorly to traditional chemotherapy or some targeted drugs, and their survival is limited.
2022 Since 2022, as KRAS targeted drugs have been approved for marketing in the United States, the global medical community has ushered in a true "breakthrough moment." Among them, Adagrasib (Adagrasib, trade name: Krazati) is considered to be another star targeted drug after Sotorasib (Sotorasib), which has quickly attracted great attention from patients and doctors.
2. R&D background and mechanism of action of adagrasib
Adagrasib was developed by Mirati Therapeutics in the United States and was later acquired by Bristol Myers Squibb (BMS). 2022 Year 12 Month, FDA accelerated approval of adagrasib for the treatment of patients with KRAS G12C mutated advanced or metastatic non-small cell lung cancer who have received at least one previous systemic therapy.
Its main mechanism of action is:
Adagrasib is an oral small molecule irreversible inhibitor that can specifically bind to KRAS G12C mutant protein.
Drugs passed with KRAS G12CBinds to the "cage pocket" site of the protein to maintain it in an inactive state, thereby blocking the cancer cell signaling pathway.
Compared with sotoracib, adagrasiib has a longer half-life (approximately 24 hours), which means that the drug concentration in the body is more stable and may bring about a longer-lasting inhibitory effect.
The breakthrough of this mechanism has enabled patients with KRAS mutations who were “incurable” in the past to finally receive truly targeted targeted solutions.
3. Efficacy data: clinical trial results show true strength
1. KRYSTAL-1 Pivotal Clinical Trial
In the global multi-center KRYSTAL-1 clinical trial, adagrasib showed encouraging data:
Objective response rate (ORR): 43%
Disease control rate (DCR): 80%
Median progression-free survival (PFS): 6.5 months
Median overall survival (OS): 12.6 months
This is a breakthrough result that significantly extends survival for patients who have failed at least one treatment regimen.
2. CNS Effectiveness of patients with metastasis
It is worth noting that about 30%-40% of lung cancer patients with KRAS mutations will develop brain metastases. KRYSTAL-1 Subgroup data show that adagrasib still shows certain efficacy in patients with brain metastases, which brings new hope to patients with complex cases.
3. Adverse reactions
Common side effects include: nausea, diarrhea, fatigue, abnormal liver function, etc. Most of the adverse reactions were controllable 1-2 grade, and about 7% of patients discontinued treatment due to serious side effects. It is better tolerated than traditional chemotherapy.
4. Comparison with Sotorasib: Which one is more suitable for patients?
Approval time: Sotorasibu was earlier (2021 year FDA approved), and adagraceib was subsequently launched.
Pharmacokinetics: Adagrasiib has a longer half-life and is expected to maintain stable efficacy.
Clinical performance: The two are close in terms of ORR and PFS , but some studies believe that adagrasib has more obvious advantages in people with brain metastases.
Price: Both drugs are priced very high in the United States, about a hundred thousand yuan/ months, which is almost unaffordable for ordinary patients.
5. Price panorama: huge gap between original research and imitation
1. US original drug price
The price of adagrasib in the United States is close to 1.7 ten thousand US dollars / months (approximately RMB 12-13 ten thousand yuan).
If the medication is used for a long time, the annual cost can be as high as 150 ten thousand yuan, which is unaffordable for the vast majority of Chinese patients.
2. Generic drug prices in Laos
Laos has launched generic adagrasibu, with each box costing about 3,000 yuan.
The ingredients are basically the same as the original drug, but the price is only that of the original drug. 1/40 About.
This is almost the only long-term affordable option for patients under financial pressure.
3. Domestic Current Situation
Adagrasib has not yet been approved for marketing in China.
Therefore, it is not possible to purchase drugs directly through regular pharmacies in China, and patients can only choose overseas drug purchase channels (cross-border medical institutions, overseas pharmacies).
6. Patients’ Frequently Asked Questions and Answers
1. When will adagrasib be available in China?
It is still in the process of clinical trials and application in China and is expected to gradually enter the approval process in the next few years, but it will be difficult to launch it in the short term.
2. Are generic drugs reliable?
The main ingredients of generic drugs produced by regular manufacturers (such as well-known pharmaceutical companies in Laos) are consistent with the original research. However, you need to purchase through formal channels to avoid fake or inferior drugs.
3. Can medical insurance reimburse me?
Since it has not yet been launched in China, it is currently not covered by medical insurance, and all costs must be paid by yourself.
4. How to choose between Adagrasib and Sotorasib?
The two drugs are similar in efficacy, and doctors generally make the decision based on patient tolerance, side effects, and drug availability.
7. Future trends:KRAS The next step in targeted therapy
1.Exploration of combination therapy
Adagorasib is being combined with PD-1/PD-L1 inhibitors (e.g.K drugs) joint research is expected to expand the indications in first-line treatment.
2.More mutation types covered
Currently focused on KRAS G12C mutation, future research may explore the feasibility of other KRAS mutation sites.
3.Improved accessibility to the Chinese market
With the advancement of clinical trials and policy support, it is expected that adagrasib may be approved for marketing in China within 3-5 years and gradually be included in medical insurance.
The emergence of adagrasib has brought unprecedented treatment hope to lung cancer patients with KRAS G12C mutations. From the perspective of efficacy, it is undoubtedly a breakthrough; from the perspective of price, it puts patients under heavy financial pressure. Before it is launched in the country, patients can only rely on overseas original drugs or Laotian generic drugs. How to strike a balance between "extending life" and "affordability" is a choice every family must face. In the future, as more KRAS targeted drugs enter the Chinese market and medical insurance negotiations are implemented, adagrasib may truly become a life-saving drug that is affordable and accessible to patients.
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References
1.Mirati Therapeutics Official announcement: https://www.mirati.com
2.FDA Approval press release (Krazati, Adagrasib): https://www.fda.gov
3.Lancet Oncology:KRYSTAL-1 Clinical Trial Results
4.BMS Adagrasiib product page
5.Abstracts of medical conferences related to cancer (ASCO, ESMO 2022)
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