| Developers: | Servier Laboratories (Servier) |
| Date of the premiere of the system: | 2022/03/10 |
| Last Release Date: | 2023/05/11 |
| Branches: | Pharmaceuticals, Medicine, Healthcare |
Content |
The main articles are:
2023
European Commission authorization for medical use as targeted therapy for two indications
On 11 May 2023, Servier announced that the European Commission had authorized ivosidenib for human use as a targeted therapy for two indications: in combination with azacitidine for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) with isocitrate dehydrogenase-1 mutation IDH1 R132, who are not indicated for standard chemotherapy; as well as in monotherapy for the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma with a mutation in the IDH1 gene who were previously treated in at least one line of therapy.
According to Servier, ivosidenib is the first and, as of May 11, 2023, the only IDH1 inhibitor approved for medical use in Europe. Based on a significant positive effect in patients with cholangiocarcinoma and AML compared to other available treatment options, this drug was assigned orphan status.
 | Since treatment methods for AML and cholangiocarcinoma are extremely limited, the prognosis for patients with these diseases was most often unfavorable. Now, thanks to the decision of the European Commission, ivosidenib has become the first IDH1 inhibitor approved for medical use in Europe, reflecting a commitment to the development of other treatments for patients with intractable cancer. noted Dr. Arnaud Lallouette, Executive Vice President, International Medical Affairs and Patient Support, Servier Group |  |
| | Mutations in the IDH1 gene are significant factors in the progression of acute myeloid leukemia and cholangiocarcinoma, diseases that are often diagnosed in advanced stages. This fact highlights the need to develop targeted therapy drugs for their treatment. Ivosidenib differs in its mechanism of action from traditional chemotherapy and opens up opportunities to improve the quality of life of patients and increase its duration. commented Dr. Philippe Gonnard, Executive Vice President, International Product Strategy, Servier Group | |
AML is a tumor disease of hematopoietic tissue characterized by rapid progression. As of May 2023, the most common type of acute leukemia affecting adults: it affects approximately 5/100,000 people in Europe, accounting for more than 20,000 new cases per year. The two-year survival rate of patients aged 75 years and older is below 10%. The European Commission approval for the treatment of AML is based on data from AGILE, an international, multicenter, double-blind, randomized, placebo-controlled, phase III clinical trial published in the New England Journal of Medicine. The results indicate a statistically significant improvement in event-free survival (AOSD) (HR hazard ratio 0.33; 95% confidence interval (CI) 0.16; 0.69) and overall survival (OS) (HR 0.44; 95%, CI 0.27, 0.73) with ivosidenib plus azacitidine versus azacitidine plus placebo.
Median OS (95% CI) in the ivosidenib + azacitidine and placebo + azacitidine groups was 24.0 (11.3, 34.1) and 7.9 (4.1, 11.3) months, respectively. In addition to the primary AOSD endpoint, all key secondary endpoints were achieved in this study, including complete remission rate, overall survival and complete remission with partial hematologic recovery, and objective response rate. These results prove that ivosidenib in combination with azacitidine is an effective treatment option for patients with newly diagnosed AML with a mutation in the IDH1 gene. The most common adverse reactions were vomiting, neutropenia, thrombocytopenia, electrocardiogram QT prolongation, insomnia.
Cholangiocarcinoma, a cancer of the bile ducts, is a rare and aggressive malignant tumor often associated with a history of cirrhosis or infectious liver disease. The prevalence of cholangiocarcinoma in Europe is 1-3 cases per 100,000 people, i.e. about 10,000 new cases of this disease are recorded annually in Europe. Five-year survival rate is 9%, but with metastasis it becomes zero. The only method of treatment is surgery, but it is possible only in a limited number of patients, while the risk of recurrence remains high. The standard of care for patients with cholangiocarcinoma who are contraindicated by surgery or whose disease has progressed after surgery is chemotherapy and immunotherapy.
The European Commission approval for cholangiocarcinoma is based on the results of the ClarIDHy clinical trial, the first and only randomized phase III trial in previously treated patients with cholangiocarcinoma with a IDH1 gene mutation. The ClarIDHy study found a statistically significant improvement in the primary endpoint - progression-free survival (PFS) - as assessed by an independent expert committee (HR 0.37; 95% CI 0.25, 0.54, <0,001). Медиана ВБП (95% ДИ) в группах ивосидениба и плацебо составила 2,7 (1,6, 4,2) и 1,4 (1,4, 1,6) месяца соответственно. Через 6 и 12 месяцев у 32% и 22% пациентов, рандомизированных для лечения ивосиденибом, не зарегистрировано событий прогрессирования или RMS, respectively, while there were no such patients in the placebo group. The most common adverse reactions were fatigue, nausea, abdominal pain, diarrhea, decreased appetite, ascites, vomiting, anemia and rash.
The use of ivosidenib monotherapy as of May 2023 is approved in the United States for the treatment of adult patients with relapsed or refractory AML with a mutation in the IDH1 gene and in monotherapy or in combination with azacitidine for the treatment of patients with newly diagnosed AML with a mutation in the IDH1 gene at the age of ≥75 years or with concomitant diseases that exclude the possibility of intensive induction chemotherapy. Ivsidenib is also legal for medical use in the USA and Australia for the treatment of previously treated patients with cholangiocarcinoma with a mutation in the IDH1 gene. In addition, the drug is approved for medical use in China for the treatment of adult patients with refractory or recurrent AML with a susceptible mutation in the IDH1 gene.
As of May 2023, the drug is approved for medical use in 27 countries of the European Union, as well as Iceland, Liechtenstein and Norway.
Recommendation for approval for medical use in Europe
On 6 March 2023, Servier reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) had positively evaluated and recommended for human use the medicinal product ivosidenib, an inhibitor of the mutant enzyme isocitrate dehydrogenase-1 (IDH1), for two indications:
- Therapy of IDH1-mutated adult patients with acute myeloid leukemia (AML) (in combination with azacitidine) who are untreated and not indicated for intensive chemotherapy.
- Treatment of adult patients with locally advanced or metastatic cholangiocarcinoma and IDH1 mutation (as monotherapy) who have received at least one prior treatment.
| | A positive assessment of the CHMP is a significant step towards making ivosidenib available to patients in the European Union. This drug was the first inhibitor of isocytrate dehydrogenase-1 (IDH1) recommended for approval for medical use in Europe for patients with acute myeloid leukemia and cholangiocarcinoma (diseases whose methods of treatment are severely limited today). stated Claude Bertrand, Executive Vice President, R&D, Servier Group | |
The CHMP positive score is based on the results of the AGILE and ClarIDHy clinical studies.
| | This is an important achievement in the treatment of patients with AML. About 8% of patients with this blood tumor have a mutation in the IDH1 gene, and for them it is an effective treatment method that improves overall survival and, importantly, quality of life. noted Professor Hartmut Dener, Medical Director of Internal Medicine at Ulm University Hospital (Germany) | |
{{quote 'author
= added Professor John Bridgewater, MD, consultant in oncology at the Institute of Research
Cancer University College and University College Hospital London (UK)|This is good news for patients with advanced cholangiocarcinoma, a disease with an extremely unfavorable prognosis for which there are a small number of treatments available for March 2023. Approximately 15% of such patients have a mutation in the IDH1 gene - this is especially important for them. We should urge the cancer community to support a personalized approach in oncology to increase the number of favorable prognoses in cancer patients who are in great need.}}
Acute myeloid leukemia is a tumor disease of hematopoietic tissue characterized by rapid progression, which is the most common acute leukemia affecting adults, with a frequency of approximately 5/100,000 inhabitants, Europe i.e., more than 20,000 new cases in Europe per year. The two-year survival rate of patients aged 75 years and older is below 10%.
Cholangiocarcinoma, a cancer of the bile ducts, is a rare and aggressive malignant tumor often associated with a history of cirrhosis or liver infections. The prevalence of cholangiocarcinoma in Europe is 1-3 cases per 100,000 people, that is, about 10,000 new cases of this disease are recorded annually in Europe. The five-year survival rate is 9%, but becomes zero with metastasis. As of March 2023, the only treatment method is surgery, but its use is possible only in a limited number of patients, while the risk of recurrence remains high. The standard method of therapy for patients with cholangiocarcinoma who are contraindicated by surgery or whose disease has progressed after surgery is chemotherapy and immunotherapy.
The use of ivosidenib in combination with azacitidine or as monotherapy is approved by the US Food and Drug Administration (FDA) for the treatment of newly diagnosed IDH1-mutated AML in patients over the age of 75 years or with comorbidities that exclude the use of intensive induction chemotherapy. The drug is also approved in the United States as a monotherapy for the treatment of adult patients with relapsed or refractory AML with a IDH1 gene mutation.
In addition, ivosidenib is approved for the treatment of previously treated adult patients with locally advanced or metastatic cholangiocarcinoma and a mutation in the IDH1 gene. The drug is approved by the Chinese National Medical Products Administration (NMPA) for the treatment of adult patients with a relapsed or refractory form of AML a susceptible mutation in the IDH1 gene.
A positive assessment of the CHMP for the two indications will be submitted to the European Commission (EC), which will make a final decision within a few months. It will apply to all 27 countries of the European Union, as well as Iceland, Norway, Northern Ireland and Liechtenstein.
2022
Efficacy for patients with acute myeloid leukemia
On April 22, 2022 , the international pharmaceutical company "" Servier reported the publication in the New England Journal of Medicine (NEJM) of the results of the phase III study of ivosidenib (tablets). The AGILE study is an international, double-blind, placebo-controlled phase III study of the use of ivosidenib in combination with (chemotherapy azacitidine) versus placebo in combination with azacitidine in adult patients with acute myeloid leukosis and IDH1 mutation who were not previously treated. The treatments study achieved primary and all major secondary endpoints, including overall survival. Servier is in contact U.S. Food and Drug Administration (FDA) with other organs around the health care world to make it possible to use medicinal the drug for this indication.
| | AML in patients with mutations in the IDH1 gene is characterized by an unfavorable prognosis and very limited possibilities for treatment, especially for newly diagnosed patients with contraindications to intensive chemotherapy. The publication in the journal NEJM of data obtained from the phase III AGILE study confirms their clinical significance and supports the company's constant desire to work for the benefit of patients with malignant tumors with mutations in the IDH1 gene. explained Dr. Susan Pandya, Vice President of Clinical Development, Head of International Development oncology and Immuno-Oncology and Metabolic Process Research in this area at Servier Pharmaceuticals | |
According to the company, data from the international phase III study AGILE indicate that ivosidenib is a targeted mutation-specific drug that has demonstrated an improvement in event-free survival (AOSD) and overall survival (OS) when used in combination with azacitidine compared with azacitidine and placebo. Ivosidenib in combination with azacitidine demonstrated a statistically significant change in AOSD (HR hazard ratio 0.33, 95 %, confidence interval CI 0.16-0.69, one-sided P-test 0.0011) 5.6 and OS (HR 0.44; 95 % CI 0.27-0.73); one-sided P-test 0.0005), with a median OS of 24.0 months in the ivosidenib + azacitidine group compared to 7.9 months in the placebo + azacitidine group.
In addition, the proportion of patients achieving complete remission was 47.2 % (n = 34/72) for the ivosidenib plus azacitidine group compared to 14.9% (n = 11/74) for the placebo plus azacitidine group (P <0,0001). Доля пациентов с полной ремиссией (ПР), а также с полной ремиссией и частичным гематологическим восстановлением (ПР + ПРг) составила 52,8 % (n = 38/72) для группы ивосидениб в комбинации с азацитидином по сравнению с 17,6 % (n = 13/74) в группе плацебо в комбинации с азацитидином (P <0,0001). Доля пациентов с объективным ответом (ЧОО) составила 62,5 % (n = 45/72) в группе ивосидениб в сочетании с азацитидином по сравнению с 18,9 % (n = 14/74) в группе плацебо в сочетании с азацитидином (p <0,0001).
Ivosidenib tablet as of April 2022 is approved in the United States as a monotherapy for the treatment of adult patients with relapsed or refractory AML with a mutation in the IDH1 gene, as well as for the treatment of adult patients with newly diagnosed AML with a mutation in the IDH1 gene aged 75 years or older or with concomitant diseases that exclude the use of intensive induction chemotherapy. This is a targeted therapy drug registered for the treatment of patients with cholangiocarcinoma and a mutation in the IDH1 gene who were previously treated.
AGILE is an international, multicenter, double-blind, randomized, placebo-controlled , phase III clinical trial to evaluate the efficacy and safety of ivosidenib in combination with azacitidine in adult patients with previously untreated acute myeloid leukemia (AML) and a IDH1 gene mutation who are not indicated for intensive chemotherapy (age 75 years or older or the presence of comorbidities, which precludes intensive induction therapy). The primary endpoint of the study is event-free survival, that is, the time from randomization to detection of therapy failure, relapse after remission or death from any cause (whichever occurs first). Treatment failure was defined as no complete remission at Week 24.
The main secondary endpoints were: complete remission rate (CR), that is, the proportion of study participants who achieved CR; overall survival (OS), that is, time from the date of randomization to the date of death from any cause; CR and complete remission with partial hematologic recovery (CRg), that is, the proportion of study participants who achieved CR and CRg; objective response rate (ORR), i.e. CR, CR with incomplete hematologic recovery (CRi) (including CR with incomplete recovery of CRi platelets), partial remission (PR), and condition without morphological signs of leukemia (SBML).
Application for approval for patients with acute myeloid leukemia and cholangiocarcinoma with IDH1 mutation
On 10 March 2022, Servier announced the submission to the European Medicines Agency (EMA) of a marketing authorization application for ivosidenib (tablets) for two indications: for first-line therapy in combination with azacitidine in patients with previously untreated acute myeloid leukemia (AML) with a mutation in the IDH1 gene who are contraindicated by intensive chemotherapy, as well as in patients with locally advanced or metastatic cholangiocarcinoma with a mutation in the IDH1 gene who have previously received treatment. The drug is an inhibitor of the mutant enzyme isocitrate dehydrogenase-1 (IDH1). Ivosidenib is a mutation-specific gene IDH1 targeted therapy drug declared for registration in Europe.
| | The European registration application is an important step towards ensuring the availability of ivosidenib, a targeted therapy for patients with IDH1-mutated acute myeloid leukemia who have previously received no treatment, and for patients with locally advanced or metastatic cholangiocarcinoma who have previously received a IDH1 gene mutation. The possibilities of therapy for these two rare types of cancer are extremely limited. We look forward to a fruitful interaction with EMA as part of the ivosidenib assessment procedure, which is the first mutation-specific targeted therapy drug declared for registration in Europe in IDH1. - noted Claude Bertrand, Executive Vice President of Research and Development of Servier Group of Companies | |
Acute myeloid leukemia (AML) is a clonal tumoral disease of the blood and bone marrow characterized by rapid progression. As of March 2022, AML is a common form of acute leukemia in adult patients and occurs in 5.06/100,000 residents, Europe with a disease rate of more than 20,000 new cases per year. The five-year survival rate among patients over 60 years of age is 20%.
Cholangiocarcinoma, cancer a bile duct, is a rare and aggressive malignancy, often associated with a history of liver cirrhosis infections or infections. The prevalence of cholangiocarcinoma in Europe is 1-3 cases per 100,000 people, that is, about 10,000 cases of this disease are recorded annually in Europe. The five-year survival rate is 9%, but becomes zero with metastasis. The only radical treatment method is surgery, but its use is possible only in a limited number of patients, while the risk of recurrence of the disease remains high. Chemotherapy is the standard treatment for patients with cholangiocarcinoma who are contraindicated or whose disease has progressed after surgery. Immunotherapy drugs and targeted therapies being developed for March 2022 allow optimizing the quality and increasing the life expectancy of patients.
| | The EMA application offers hope that ivosidenib will soon become available for patients with newly diagnosed AML with a mutation in the IDH1 gene, as well as for patients with locally advanced or metastatic cholangiocarcinoma with a mutation in the IDH1 gene previously treated. explained by Dr. Philippe Gonnard, Executive Vice President of the International Department for medical Issues and Work with Patient Organizations of the Servier Group of Companies | |
This registration application includes 27 countries of the European Union, as well as Iceland, Liechtenstein and Norway.
Ivosideni as of March 2022 is approved in the United States as a monotherapy for the treatment of adult patients with relapsed or refractory AML with a mutation in the IDH1 gene, as well as for the treatment of adult patients with newly diagnosed AML with a mutation in the IDH1 gene aged 75 years or older or with concomitant diseases that exclude the use of intensive induction chemotherapy. In addition, since 2021, ivosidenib has been a targeted therapy approved by the US Food and Drug Administration (FDA) for use in patients with locally advanced or metastatic cholangiocarcinoma with a IDH1 gene mutation previously treated. Ivosidenib for March 2022 is approved by the National Medical Products Administration of China (NMPA) for the treatment of adult patients with relapsed or refractory AML and a susceptible mutation in the IDH1 gene.
| The site content is translated by machine translation software powered by PROMT. The machine-translated articles are not always perfect and may contain errors in vocabulary, syntax or grammar. Read original article If you find inaccuracies or errors in the results of machine translation, please write to editor@tadviser.ru. We will make every effort to correct them as soon as possible. |