In the first half of 2020, China's first class of new drugs again achieved a new record.

From 2018, China's domestic innovative drugs into a period of vigorous development, in the domestic innovation drug review and approval continue to speed up, new drug creation major special, national key research and development programs and other policies supported, a number of effective, safe and reliable, price advantages of outstanding domestic innovative drugs are breaking the monopoly of foreign pharmaceutical companies, to fill the clinical urgent need for domestic drugs blank.
recently, the State Drug Administration has also officially launched a breakthrough therapeutic drugs, conditional approval of the listing application and priority review of three new drug incentive procedures for the pilot version, for me-better /best of the local innovative drugs will bring further benefits.
Figure 1 In recent years, China's first class of innovative drugs approved quantity, note: 1 new drug, that is, domestic and foreign are not listed in the first half of 2020, the State Drug Administration approved a total of 6 new drugs: 5 therapeutic drugs and 1 diagnostic reagents;
local innovative drugs are included in the national major new drug creation special, in the Fda under the priority review of the approved listing, of which Zebutinib and ametinib for the Drug Administration conditional approval of the listed varieties.
Table 1 List of Domestic 1 New Drug Approved Products in the First Half of 2020 Note: Zhifei Bio's Diagnostic Reagents and Novartis's Sinimod tablets are not the focus of this analysis 1, from the point of view of clinical benefits, these local innovative drugs have safety or effectiveness data comparable with multinational companies, and even some indicators present me-better /Best Trend 1.1 The first approved variety in China and the United States, Zebutini Capsules, by the end of 2019, Zebutinib of Baiji Shenzhou became the first domestically innovative drug approved for sale in the United States at the end of 2019 when Zebutinib was approved by the FDA for the treatment of patients with adult cell lymphoma (MCL) who had previously received at least one treatment.
in June this year, the product was approved in The country for use in adult synthroma lymphoma (MCL) patients who have previously received at least one treatment and for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who have previously received at least one treatment.
the target's first listed drug was ibtinib, approved in 2013, but the first generation of BTK inhibitors had low oral bioavailability (F.lt;10%), a large dose, narrow treatment windows, and inhibition of wild epidermal growth factor receptors (EGFR), causing adverse reactions such as rashes and diarrhea, compared to higher target selectivity and safety.
Zebutinib's approval for CLL/SLL is based on the results of a single-arm, critical Phase II clinical trial conducted in China (NCT03206918; BGB-3111-205), which included 91 patients (82 of whom were R/R CLL patients; 9 were R/R S LL patients).
outcome of the cancer mitigation assessment of CLL patients and SLL patients by the Independent Review Committee (IRC) in accordance with the revised iwCLL Guidelines (2008) and Lugano (2014) classification criteria. The total remission rate (ORR) was 62.6 percent, including 3.3 percent total remission (CR) and 59.3 percent partial remission (PR), and another 22 percent of patients received partial remission (PR-L) with lymphocytic growth. The most common serious adverse reaction in
was pneumonia (11.0%).
Zebutinib domestic approval of MCL is based on the results of a single-arm, critical Phase II clinical trial in 86 patients in China (clinicaltrials.gov registration number: NCT03206970; BGB-3111-206), the median treatment treatment previously accepted by these patients was 2 (1-4), 38.4% of patients had a high-risk MIPI score, and 15 patients had TP53 mutations.
results of efficacy assessed by the Independent Review Committee (IRC) based on the Lugano (2014) classification criteria show that the total remission rate after Zebutinib was 83.7%, of which the total mitigation rate was 68.6% and the partial mitigation rate was 15.1%. the most common serious adverse reactions (more than 2%) of
were infectious pneumonia (8.1%), haemorrhage (2.3%) and platelet reduction (2.3%).
, for example, a summary analysis of ibtinib clinical studies on similar baseline studies of recurrent refractive refractive refractive enthromyclioma (PCYC-1104/SPARK/RAY) (II), the median previous treatment treatment rate for 370 treated patients was 2 (1-9)), 73.2% received treatment from two and above options, and the summary analysis showed that the total mitigation rate was 69.7%, the total mitigation rate was only 27.0%, the partial mitigation rate was 42.7%, and the median duration of the remission was 21.8 months.
and at the just-concluded 2020 ASCO online meeting, Baiji released updated data from its BTK inhibitor Zebutinib ibibibibininib in the ASPEN Global Head-to-Head III clinical trial in the treatment of patients with Fahrenheit polycylobinemia (WM).
new follow-up data show that Zebutinib shows greater safety and tolerance than ibtini, while achieving higher full/very partial mitigation rates.
at the median follow-up time was 24.2 months, in the overall intentional treatment population, the total relief and very good partial mitigation rate assessed by the researchers combined (CR-VGPR), with Zebutinib 30.4% compared to ibtinib 18.2% (P-0.03), respectively, compared to the data as of August 2019, the gap widened further and the difference was even more significant.
figure 2 ASPEN clinical study endpoint, compared to ibtinib, Zebutinib has significantly improved safety and tolerance, adverse events (AE) overall lower risk, especially in atrial fibrillation (Zebutini 3.0% vs. Ibtini 18.4%) and other adverse events that require special attention, showing greater safety.
as the follow-up time increased, there were no new patients in the Zebutinib trial group who were treated with AE interruption.
overall, in both groups, the overall proportion of treatment interruptions due to AE was 4.0 percent compared to ibtinib 9.2 percent, while the proportion of patients who died from AE was 1.0 percent compared to ibtinib 4.1 percent.
the first Chinese-American new drug approved at the same time, Zebutinib, compared with the first generation of BTK inhibitors, in addition to the mitigation rate has a good performance, but also showed higher safety and tolerance, has become China's innovative drug to the world representative.
1.2 Domestic first three-generation EGFR-targeted drug - amatinib amatinib amatinib developed for Hausson Pharmaceuticals to develop and market the first domestic three-generation EGFR target drug, indications for the past tKI treatment or treatment of disease progression, and the presence of EGFR T790M positive local late metastatic non-small cell lung cancer patients.
in the late NSCLC population in China, about 50% of the EGFR gene mutation, currently targeted drugs for EGFR mutation has been listed in a number of products, but for the first generation of drug treatment after the disease progression T790M positive NSCLC patients (about half) there is still a large clinical demand for drug use. data released
at the 2020 AACR Annual Meeting show that 224 patients (23 of which had at least one intracranial measurable lesions) in a local late or metastatic NSCLC clinical study of EGFR T790M mutation-positive eGFR T790M in treatment of first-line EGFR-TKI treatment) 11.4 months of median follow-up, total population mitigation rate (ORR) was 68.9%, disease control rate (DCR) was 93.4%, median progression-free survival (PFS) was 12.3 months, and median mitigation duration (DOR) was 12.4 months.
brain metastasis, ORR was 60.9%, DCR was 91.3%, median PFS was 10.8 months, and median DOR was 11.3 months.
Figure 3 Amitinib II clinical clinical studies results and the first three-generation EGFR inhibitor ochitinib import approval is mainly based on the AURA17 study conducted in The Asia Pacific region, of which 166 evaluatable patient results showed a total remission rate of 62%, disease control rate of 88%, median sustained remission time of 9.9 months, median progression survival of 9.7 months.
amatinib is the first domestically produced three-generation EGFR inhibitor and the second third-generation EGFR inhibitor in the world, and the clinical data of the second-line drug use show that amitinib has become the world's first medium-term progression-free survival of more than 1 year of three-generation EGFR inhibitors.
amatinib in the patients and doctors to bring more treatment options at the same time, but also demonstrated the strength of the domestic innovative drugs continue to improve.
1.3 The second class Of C treatment class 1 new drug - hydrochloric acid conodite conate conodic bio-developed hydrochloric acid conodite co-developed co-product seroperivir capsule sonofin is the second approved new drug for hepatitis C treatment, combined with Sorphosphatebve, the treatment of primary treatment or interferon-administered gene 1, 2, 3, 6 adult chronic hepatitis C virus infection, can be combined or not reimbursable hepatitis c.
Phase II clinical studies of co-use with Soropabevir included 110 cases of initial lysis of gene 1, 2, 3 or 6 HCV infections, of which 10.9% combined with proliferating cirrhosis, and 98.2% of the patients who intended to treat the disease at 12 weeks to achieve continuous virological response (SVR12).
Figure 4 Colopiwe and Sophosibwe combined with Thesaphosbuwe combined with the results of another domestic mainland single-arm, open label, Phase III trial data show that in 371 patients with hepatitis C, the co-use of the total SVR12 between the co-use of the co-use of the co-use of the co-use of the co-use of the co-use of the sorphosbuwe was 97%.
Figure 5 Colopiwe and Sophosbwe co-use Phase III clinical studies results and in the previously listed similar imports, Gilead's Sophosbuwe/ Vipatavir compound monolith and Abbvie's Gcararewe/pyrithavir can be used for the treatment of patients with full gene type hepatitis C, and also have excellent therapeutic results.
domestic class 1 new drug hydrochloric acid conodite for the domestic hepatitis C patients brought more treatment options, further solve the problem of partial drug accessibility, and then jointly follow-up Keinger led the approval of the sophosbuvir generic drug, will bring more affordable effective treatment for domestic hepatitis C patients.
1.4 The first domestic high-selectivity M1/M3 choline receptor antagonist - phenyl cyclomine ammonium bromide nasal spray in March 2020, Silver Valley Pharmaceuticals' benzodiazepine combitean nasal spray was approved for sale, the drug is the first synthesis of high-selectivity M1 in China /M3 choline receptor antagonists, may be by inhibiting choline nerve-mediated gland secretion and inflammatory response, to alleviate the symptoms of mutated rhinitis, clinically approved indications for the improvement of the reaction of rhinitis caused by runny nose, nasal congestion, nasal itch and sneezing symptoms.
ammonium phenyl cyclomine was the most selective to M3 receptors, second in M1 receptors and m2 receptors with the lowest selectivity, which was close to the selectivity of M3 and M1 receptors, significantly higher than the selectivity of M2 receptors, with low toxic side effects, safe use, and wide range of people.
As the drug declaration report has not yet been published and the results of Phase III clinical trials have not yet been published, only the results of human tolerance studies have been published, this trial can be tolerated in a single dose between 125-2,000 sg, the maximum tolerable dose of 2,000 ?g, 1,500 g and 2,000 sg continuous administration, 4 consecutive administrations, 14 d, safe.
2, from the economic benefits point of view, the local class 1 new drug is expected to further reduce the patient's medical burden, expand the patient's use of the population, further reduce the social disease medical burden of the medical burden of the zebuttini is currently priced significantly lower than the first generation of BTK inhibitor ibtenini pricing, as described above The monthly treatment cost of Zebtinib is less than half the original price of the latter, and is comparable to the price negotiated with ibtini capsules, even if the monthly treatment costs of MCL indications are lower than the monthly treatment costs of ibtinib capsules; Howson Pharmaceuticals' methyl sulfonate amatinib The tablets are slightly higher than the cost of a pre-a-month treatment for AstraZeneca's Ochtinib; the monthly cost of the hydrochloric acid conodin conodin conodin conodis is lower than that of the same target,100-time Mesiquibo's dalateve tablets, both of which are higher than the two years after the health-care negotiations In addition, both need to be used in conjunction with other such as saphosbuvir or Ashurive, the monthly cost of treatment may be higher, although the Sophosbuvir generic drug developed by Theine Collar has been approved, the specific follow-up price how to set, There is more uncertainty.
Figure 6 The number of previous medical insurance negotiations and the reduction of new included drug prices China has organized four drug medical insurance access negotiations, four negotiations on the average decline in drug prices is 55%, and the decline in the last three years has a further trend of expansion.
if the first half of the approval of the four class 1 new drugs followed by the average decline negotiated, with Zebutinib as the representative of the local class 1 new drug is expected to further reduce the medical burden of patients, expand the patient's use of the population, and further reduce the burden of social diseases medical.
and so far, from the drug database can be seen, China's class 1 new drug is still in the NDA / BLA in the progress, including local innovative drugs and imports of class 1 new drug.
encourage foreign-funded enterprises to conduct original development and clinical research in China, which will not only rapidly enhance the ability of China's innovative drug clinical research, but also promote international cooperation and exchanges.
and the emergence of more high-quality and low-cost local innovative drugs, to a certain extent, can alleviate the major disease patients access to drugs and the burden of medication, so that the people's drug safety and convenience to be guaranteed, while the health insurance fund difficulties will also be difficult to see the day.
from this point of view, the development of the local innovative pharmaceutical industry in China's pharmaceutical industry, the burden of medical expenses, the health of China's 2030 plan, and even China's national security has a very important role in promoting.
References. Guo Zongju. The anti-tumor drug Zebutinib, created in China, Zebutinib. The Journal of Pharmacy: 1-10.2020-07-09. Rule S, Dreyling M, Goy A, et al. Ibrutinib for the treatment of the relapsed/refrac.