Although the number of patients with hematologic tumors is relatively small compared with solid tumors, the hematological tumor drug market should not be underestimated due to factors such as the long medication cycle of patients and the cumulative effect of patients.
Because of this, hematologic tumors have always been an area that MNC has been betting heavily on, and Biotech has also hoarded heavy troops here. Compared with big pharma, perhaps biotech's investment is more worth looking forward to.
The core lies in,In the era of technological discovery, the progress of new anti-tumor drugs is changing with each passing day, the development direction has become more diversified, and more flexible and efficient biotech will continue to subvert the clinical landscape.
After all, our pursuit of "dechemization and detransplantation" of hematologic tumors continues. A few days ago, at the "Hematological Oncology Innovative Drug Summit Forum and Global Launch Conference for New Indications of Nerico", many top domestic experts in hematological tumors specifically emphasized this point.
This means that hematologic malignancies are still an escalating race. The continuous attack of Nerick and Ascentage Pharma is a sample to observe the escalating competition in the field of hematological tumors.
01 Beyond - Nellik that continues to surpass
In the field of hematological tumors, although there are many options for TKI, and the best path is relatively certain, strong latecomers can still quickly become "spoilers". Right now, the "New Army" Nerick is telling such a story.
From the perspective of existing indications, Nerick has solved the urgent clinical needs of some patients with chronic myeloid leukemia.
The first indication for Nerick is for adult patients with T315I mutations in the chronic phase (CP) or accelerated phase (AP) of CML, breaking the dilemma of this group of patients without drugs.
The second indication is for the treatment of adult patients with chronic myeloid leukemia who are resistant to or intolerant to the first and second generation TKIs, which has jumped out of the previous limitation of only being suitable for patients with T315I mutations, and has expanded the size of the patient population by 3-4 times.
The proportion of patients in the chronic phase who are newly treated is about 20-30%, the proportion of patients in the accelerated phase will be higher, and some patients are intolerant. At the "Hematological Tumor Innovative Drug Summit Forum and Global Launch Conference for New Indications of Nelik", Professor Jiang Qian of Peking University People's Hospital, the principal investigator of Nelik China's clinical trial, said that the proportion of resistance or intolerance to first- and second-generation drugs is not low.
But actually,In the case of meeting the needs of the existing group, Naelik will further "disrupt" the situation and gradually "encroach" on the space of other TKIs. The core logic lies in two points:
First, in the field of CML, the order in which Nerick is used will continue to move forward.
At present, in some overseas countries, second-generation TKI has become the first choice for first-line drugs. So, after the second-generation TKI is the first-line **, should it be replaced by another second-generation TKI** or directly replaced by the third-generation TKI**?
In the discussion session of the "Hematological Tumor Innovative Drug Summit Forum and Nerik New Indication Global Launch Conference", some experts mentioned that it would be a better choice to directly use the third-generation TKI.
Professor Li Weiming of the Department of Hematology, Tongji Medical College of Huazhong University of Science and Technology, believes that the efficacy of second-generation TKIS in second-line CML patients is not good, and the use of third-generation TKI as the second-line ** can make CML patients benefit more.
This view can be supported by overseas real-world data. At present, 75% of patients who are resistant to first-line TKIs in Italy** will directly use third-generation TKIs. This means that in the case of a change in the first-line medication, the order of use of Nerico will also be moved forward.
In this regard, Professor Li Weiming said that the exploration of Naelik in the field of CML second-line ** will provide a more effective option for more TKI-resistant patients in China, and is expected to become the preferred solution for the second-line ** of drug-resistant CML patients.
In fact, it is not only domestic experts who are looking forward to this from Nerick. Nerico, which is not yet available on the global scale, has been included in the latest version of the NCCN (National Comprehensive Cancer Network) CML** guidelines. In this guide, Nerik is considered one of the potential new**.
This marks that the outstanding effect of Nerik has been recognized by the international oncology community, laying a solid foundation for its internationalization. After all, the NCCN's updated guidelines for cancer are not only the standard for clinical decision-making in the field of oncology in the United States, but also one of the most widely used guidelines in clinical practice of oncology in the world.
Second, in the ALL field, Nerick will intervene in the first link earlier.
The current trend of hematological malignancies is to give more effective and safer drugs to patients earlier, rather than waiting until patients are resistant to drugs, including the immune system, before using them. This trend is even more pronounced in the "sinister" Philadelphia chromosome-positive (pH+) field of acute lymphoblastic leukemia (ALL).
At the "Hematological Oncology Innovative Drug Summit Forum and Global Launch Conference for New Indications of Nerico", some clinical experts mentioned in the discussion that if patients under the second-generation TKI** cannot achieve CMR within three months, they will change to the third-generation TKI as soon as possible to strive for better clinical benefits.
In the case of PH+ ALL patients with whole myeloid origin, in the case that MRD can not be turned negative by traditional means, stronger molecular targeting will be done as soon as possible, such as the introduction of third-generation TKI represented by Nerico.
Professor Zhou Hongsheng of Nanfang Hospital of Southern Medical University said that the existing research data show that the ** regimen based on Nerik can achieve a high CMR of 3 months, which is expected to become the cornerstone of the first-line PH+ ALL patients**.
That is to say, in the context of "early intervention of good drugs**", Nerico, which has good effect and outstanding safety, will bear more.
Obviously,Although it was released as a third-generation TKI character, the ability of Nerik is not limited to this, and the better efficacy and safety make it continue to attack. This is a reflection of the escalating competition for hematologic tumors.
/ 02 / "Ambitious"Ascentage Pharma
In the field of hematologic tumors, the appearance of Nerick is not accidental. The essence is that the upward wave of biotechnology in the past few years has given birth to many ambitious companies: a group of biotech that wants to make greater achievements in hematologic tumors.
This is another manifestation of the escalation of competition for hematologic tumors. For example, Nerick is only the starting point of Ascentage Pharmaceutical's hematologic tumor layout, and according to the company's plan, its development path is from "C to A to M".
The so-called C refers to CML (chronic myeloid leukemia) and CLL (chronic lymphocytic leukemia); A refers to ALL (acute lymphoblastic leukemia) and AML (acute myeloid leukemia); M refers to MDS (myelodysplastic syndrome) and MM (multiple myeloma).
Of course, this process is not done by Nerick alone, but also includes the BCL-2 inhibitor APG-2575. Among them, Nerick participates in the competition of "C" and "A", while APG-2575 participates in the competition of "C, A, M" throughout the whole process.
WhileSupporting Ascentage's ambitions is the hard power of Nerik and APG-2575.
Currently,Nelik is already a BIC drug in this field. Although no head-to-head experiments have been carried out, Nerick still has an excellent ** effect on patients who have failed to respond to similar drugs**, which can prove that its efficacy is better.
In a clinical study of patients who had previously received deep** refractory CML and pH+ALL, Nerik had a CCYR rate of 53% and a 38% mM rate in patients who failed ponatinib**; For patients who failed the allosteric inhibitor ASCIMINIB**, the CCYR and MMR rates were 43 and 38 percent, respectively.
In addition, Nerick has obvious safety advantages. Ponatinib had events such as vascular occlusion, heart failure and hepatotoxicity, and was once withdrawn from the market, and then re-marketed with a black box warning. While the Nericotoxin*** is lower, AEs are mainly hematologic toxicity and are easy to manage. These advantages will support Nerick to go further in the global competition.
APG-2575 also has the potential to become a BIC drug, and multiple pivotal clinical data have shown that it has both efficacy and safety benefits.
For example, in terms of safety, APG-2575 has a lower probability of tumor lysis syndrome (TLS) and a more rapid dose escalation compared to venetoclax, a FIC drug in this field.
Specifically, venetoclax can only be administered in weekly dose escalation for up to 5 weeks until the target dose is reached, while APG-2575 is administered in daily escalation. This also makes the comprehensive competitive advantage of APG-2575 extremely obvious.
At the "Hematological Oncology Innovative Drug Summit Forum and Global Launch Conference for New Indications of Nelik", Professor Wu Depei of the First Affiliated Hospital of Soochow University believes that the competitive advantages of APG-2575 will be reflected in three aspects:
First, the advantage of diagnosis and treatment effect, that is, it brings a rapid response to patients and has good safety;
second, to improve patient compliance, as APG-2575 can reach the ** dose in a shorter period of time and is able to reduce hospital costs;
Third, it can significantly improve the efficiency of diagnosis and treatment in hospitals, because APG-2575 can improve the turnover rate and utilization rate of beds.
In addition, APG-2575 has not been found to have a "drug-drug interaction" problem in clinical practice, which brings more possibilities to it. This means that there is no need to worry about whether APG-2575 can be used in combination with some drugs, and there is no need to reduce the dose due to drug interactions in the combination exploration** that affects the efficacy.
Because more importantly, Dr. Yang Dajun, Chairman and CEO of Ascentage Pharma, pointed out that Nerick and APG-2575 are not independent of each other, but can achieve the effect of "king fried" through joint efforts.
From the current point of view, the combination of Nerick and APG-2575 is expected to achieve two goals through the "1+1>2" approach.
The first is to "move forward" and promote the "de-chemotherapy and de-transplantation" of some existing indications. For example, the combination** has the possibility of allowing patients with acute showering to benefit in the long term without transplantation;
The second is to "go backwards" to solve the problem of drug resistance of the two types of drugs. For TKI, drug resistance is unavoidable, and solving the problem of drug resistance has always been a long-term need.
Although the exploration of the combination of the two drugs is still in the clinical stage, it provides us with another dimension to understand the competition in hematologic malignanciesEcological warfare has become an indispensable tool in the field of hematologic tumors.
03 How to keep competitors out
Referring to the development of overseas enterprises, the competition in the field of hematological tumors is no longer the competition of a single drug, but an ecological coupling and collaborative operation.
The most typical is Johnson & Johnson, which redefines the model of multiple myeloma through the joint strategy of monoclonal antibody, bispecific antibody and CAR-T product matrix, with the aim of making latecomers have no way out.
In essence,This is also the layout idea of Ascentage Pharma in the field of hematological tumors, that is, through a series of product layouts, to achieve the purpose of establishing a deep moat.
In addition to Nerick and APG-2575, another important layout of Ascentage Pharma in the field of hematological mharmacies is ADM2-P53 inhibitor APG-115.
In almost all cancer cells, there are abnormalities in the MDM2-P53 pathway, including p53 mutations and MDM2 overexpression, resulting in the loss of p53 tumor suppressant activity. Therefore, the use of small molecule inhibitors to block the protein-protein interaction between MDM2-p53 is a promising cancer strategy.
The addition of APG-115 will enhance the comprehensive strength of Ascentage Pharma's hematologic tumor layout.
On the one hand, APG-115 can be used in combination with BCL-2 inhibitors to achieve a synthetic lethal effect, bringing unlimited space for chemo-free utilization for various hematological tumors.
On the other hand, APG-115 will also be one of the stepping stones for the development of Ascentage Pharma's innovative drugs for children. "China also attaches great importance to the development of innovative drugs for children, so we hope to use APG-115 to promote the research and development of new drugs for children. At the "Hematological Oncology Innovative Drug Summit Forum and Global Launch Conference for New Indications of Neric", Dr. Zhai Yifan, Chief Medical Officer of Ascentage Pharma, said.
At present, APG-115 has obtained 2 FDA rare disease designations for pediatric rare diseases, with the indications of ** pediatric neuroblastoma and pediatric retinoblastoma, respectively.
In addition, Ascentage Pharma is also actively promoting the research and development of new pipelines. For example, the company's EED inhibitor APG-5918 has shown positive potential for the treatment of anemia caused by chronic kidney disease or chemotherapy, and also has broad clinical application prospects in solid tumors and hematological tumors.
Obviously, with the advancement of multiple pipelines such as APG-115, Ascentage Pharma's position in the hematologic tumor market will continue to move forward.
For domestic pharmaceutical companies, the choice of Johnson & Johnson and Ascentage Pharma is not a revelation.
In the field of biopharmaceuticals, in the face of the cruel and indifferent law of the jungle, how to find their own way to survive is a problem that every pharmaceutical company needs to think about.
Nowadays, the layout of the field of hematological tumors is becoming clearer, that is, the "ecological coupling" method. Whoever can build a more competitive portfolio can keep competitors out.