From Beijing, where its headquarters is based, the BeiGene company is the first all-Chinese biotech company to land in Italy with its load of immunotherapy molecules developed to help fight cancer of the esophagus (very common in Asian countries including just China), lung, head-neck and even blood. In just ten years, he introduced 11 new drugs into clinical practice. Today BeiGene presents its pipeline currently consisting of over 20 molecules.
Cancer of the esophagus: risk factors
In the last five years, in Italy, new cases of esophageal cancer have increased by 26%, from 1,900 to 2,400, but mortality has decreased by 12.4% in women and 6.7% in men. “Obesity is a major risk factor for non-squamous histology of distal esophageal carcinoma, which has become the most frequent in Western countries – he says Stefano Cascinu, head of the Irccs Oncological Medicine Unit of the San Raffaele Hospital in Milan and professor of Medical Oncology at the Vita-Salute San Raffaele University. “Alcohol abuse and cigarette smoking, on the other hand, are closely related to the scaly form, which represents about 40% of the total cases we treat at ‘San Raffaele’, one of the main centers of reference for surgery and treatment of this neoplasm. The difference is substantial for the purposes of treatment before surgery “.
Cancer of the esophagus in an advanced stage
Unfortunately, however, about two thirds of cases are discovered already at an advanced stage, in which survival does not exceed 10 months. “Too many patients – continues Cascinu – discover the disease in an advanced stage, no longer operable. And they are very fragile people, often also affected by other diseases, with a low quality of life. Hence the need for effective and tolerable therapies. The turning point can come from immunotherapy, which strengthens the immune system against cancer ”. One of the innovative molecules developed by BeiGene, tislelizumab, has shown a marked improvement in survival in patients with unresectable or metastatic advanced squamous esophageal cancer and already treated. “In the international phase 3 study, ‘Rationale 302’ – explains Cascinu – 512 patients from 11 countries with unresectable or metastatic advanced squamous esophageal cancer and already treated were enrolled. Tislelizumab was compared with chemotherapy and, for the first time, there was an improvement in overall survival. Immunotherapy is destined to play a fundamental role also in the other phases of the disease, from preoperative to the first line “.
Immuotherapy for head and neck and lung cancers
Another infrequent neoplasm that is strongly conditioned by risk factors such as smoking and alcohol is that of the head and neck. In 2020, 9,900 new diagnoses were estimated in Italy. “In a phase 1 study, tislelizumab monotherapy showed response rates of about 15% in patients with advanced disease,” explains the head of Irccs San Raffaele. “Even in this pathology, immunotherapy can become a milestone, just as it is already a consolidated reality in a very frequent tumor like that of the lung. In the international phase 3 study ‘Rationale 303’2, recently presented at the AACR (American Association for Cancer Research) congress, in 805 patients with advanced or metastatic non-small cell lung cancer, tislelizumab, in the second and third lines, has showed a median overall survival of 17.2 months compared to 11.9 months with chemotherapy and the one-year progression-free survival rate reached 23.3% with the new immunotherapy molecule compared to 5.7% with chemotherapy “. Tislelizumab is being tested and in clinical development in several types of cancer. BeiGene recently entered into a partnership with Novartis Pharma, granting Novartis the rights to develop, manufacture and market tislelizumab in North America, Europe and Japan.
La macroglobulinemia di Waldenstrom
New options are also available for patients suffering from a very rare blood cancer such as Waldenstrom’s macroglobulinemia which affects around 250 people in Italy every year. It is an indolent lymphoma, so patients usually remain asymptomatic for a long time without the need for treatment. “The disease – he explains Paolo Ghia, Director of the Strategic Research Program on Chronic Lymphatic Leukemia at the Irccs San Raffaele Hospital in Milan and Professor of Medical Oncology at the Vita-Salute San Raffaele University – is characterized by the presence of a protein, the monoclonal component M, which is accumulates in the blood. When it reaches high levels it can cause symptoms, such as dizziness, tingling, visual disturbances and nosebleeds, caused by the increase in the viscosity of the blood that fails to reach the peripheral districts, and therefore treatment can be started “. Other reasons for initiating therapy are swollen lymph nodes or decreased red blood cells (anemia) or blood platelets.
The therapies
Median survival is approximately 5-10 years. First-line treatment is immuno-chemotherapy. Secondly, targeted therapies and, in particular, BTK inhibitors can be used. “Zanubrutinib is a new generation BTK inhibitor that is characterized by high efficacy and tolerability,” continues Ghia. “In the ‘Aspen’ study on about 200 patients, both in the first line and in relapsed or refractory patients, the molecule demonstrated an efficacy similar to ibrutinib, a first generation BTK inhibitor, while guaranteeing a better quality of life, with effects less frequent collateral. The response rate was 77%, with 85% of patients without disease progression at 18 months ”. The incidence and severity of most BTK inhibitor toxicities (including atrial fibrillation) were lower with zanubrutinib than with ibrutinib. And, in a study published in the journal Blood, the overall response rate with zanubrutinib reached 96% in long-term treatment, with complete responses of 45% and a good tolerability profile in both first-line and relapsed patients. or refractory.
Chronic lymphocytic leukemia
Zanubrutinib has been approved for the treatment of Waldenstrom’s macroglobulinemia in Canada (1 March 2021) and approval by the European regulatory body (EMA) is expected in 2021. Zanubrutinib has also shown promising results in chronic lymphocytic leukemia. which every year in Italy records about 2,800 new diagnoses. “Enlarged lymph nodes, anemia and thrombocytopenia with fever and a feeling of fatigue are manifestations of the disease, which is one of the indolent lymphomas,” continues Ghia. In the journal ‘Haematologica’, data from an arm of the ‘Sequoia’ study on 109 patients at high risk due to a genetic abnormality, the deletion of chromosome 17 and treated with zanubrutinib were published. It is one of the few studies in the world that has included this specific population, which does not respond to immuno-chemotherapy and therefore had a life expectancy of no more than 3 years after starting treatment. “The response rate – adds Ghia – was 94%, with 89% of patients without disease progression at 18 months. This makes it easier to manage even the most severe forms of long-term leukemia. The recent revision of the European guidelines has reduced the number of patients eligible for immunochemotherapy in the first line, so that targeted therapies are destined to increasingly become the standard of care even in previously untreated patients ”. Zanubrutinib is approved for the treatment of patients with chronic lymphocytic leukemia by the China National Medical Products Administration (NMPA).
Mantle cell lymphoma
Another cancer affecting B lymphocytes, such as Waldenstrom’s macroglobulinemia and chronic lymphocytic leukemia, is mantle cell lymphoma, which registers 500 new cases every year in Italy with a median survival of about 5 years. “It is more aggressive than the other two types of lymphoma and requires therapies that guarantee deeper responses to achieve greater control of the disease,” explains Ghia. “The first approval of zanubrutinib in the United States concerns precisely this more aggressive form of non-Hodgkin’s lymphoma. This is the first study entirely conducted in China that led to approval by the American regulatory body (FDA) and the China National Medical Products Administration. The overall response was 84%, the complete response, which indicates the absence of the disease in radiological examinations such as CT and PET, was 69% ”.
Why a biotech in China
There is a lot of fervor and anticipation regarding BeiGene’s therapeutic innovations. More than 60 clinical trials are currently underway in 35 countries, ranging from gastrointestinal and breast cancers to melanoma to gynecological malignancies. And in Italy about 50 hematology centers are involved in experiments promoted by the biotech company. Singular is the history of the company which has among its founders a ‘man of science’, Xiaodong Wang, founder and director of the National Institute of Biological Sciences in Beijing since 2003 as well as a member of the National Academy of Science and the Chinese Academy of Sciences. . “Just last week – he says Claudia Rigamonti, BioGene’s medical director for Italy and the Balkans – received recognition from the American Association for Cancer Research for his studies on apoptosis. Today BeiGene employs more than 5,400 people worldwide, with 23 offices on 5 continents, of which 1,600 are dedicated to research. Our goal is to offer effective therapies to improve the quality of life of patients affected by oncological and haematological diseases. The company was born in China also to bring innovative drugs to this country that are often not granted ”.
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