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Challenge the best-China's biotech goes international, series of reports (3) - who can keep the clouds open and see the moon when there is no storm

 Last Update: 2022-10-25
 Source: Internet
 Author: User

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preface

With the continuous enhancement of the innovation ability of Chinese pharmaceutical companies, clinical development is gradually in line with the latest international standards, and gratifying results
have been continuously achieved.
Recently, Conrad Biopharma announced that the pivotal clinical trial of CBP-201 in China for the treatment of moderate to severe atopic dermatitis successfully met the primary endpoint and all key secondary endpoints, with good safety and efficacy
.
It is worth noting the scientific and rigorous design of this key clinical study, and the use of highly reliable data processing and statistical methods, and the results have highly significant differences and reached the international first-class level
.
The announcement of this result further proves the competitiveness of the product, and also reflects the process
of China Biotech actively responding to challenges and continuously improving, from growth to maturity.

Conrad Biopharma announced that the pivotal clinical trial in China of CBP-201 for the treatment of moderate to severe atopic dermatitis successfully met the primary endpoint and all key secondary endpoints with good safety and efficacy
.

body

The pivotal Chinese clinical study of Conrad CBP-201 for the treatment of moderate to severe atopic dermatitis (AD) reached the primary endpoint, and compared with the clinical data of similar drugs already on the market, it showed the overall equivalent or even some indicators of better results, providing CBP-201 with efficacy and safety data
that can be used to support marketing applications.

Based on 16 weeks of data analysis, the proportion of participants meeting the primary endpoint (IGA score of 0/1 and ≥ points from baseline) was significantly higher than that in the placebo group (30.
3 versus 7.
5 percent), as detailed in the chart below:

Figure 1.
Primary clinical endpoints: proportion of participants with an IGA score of 0/1 at week 16 and a decrease of ≥ 2 points from baseline (CBP-201 vs placebo); (This analysis is based on 255 Chinese patients with moderate to severe AD who were administered Q2W, including 170 in the CBP-201 group and 85 in the placebo group; , **, *representing P<0.
001, <0.
01, <0.
05, respectively, compared to placebo)

Figure 1.
Primary clinical endpoint: proportion of participants with an IGA score of 0/1 at week 16 and a decrease of ≥2 points from baseline (CBP-201 vs placebo)

The study also met all key secondary endpoints: at week 16, the proportion of participants achieving EASI-50, EASI-75, and EASI-90 in the CBP-201 treatment group was significantly higher than in the placebo group, with response rates of 83.
1 versus 41.
1 percent, 62.
9 versus 23.
4 percent, and 35.
8 versus 6.
3 percent, respectively (see Figure 2); The proportion of participants in the CBP-201 treatment group with PP-NRS (Peak Pruritus Digital Assessment Scale) scores decreased by ≥3 and ≥4 points from baseline significantly higher than in the placebo group, at 46.
7 versus 16.
7 versus 35 versus 9.
6 percent, respectively; The percentage reduction in PP-NRS scores from baseline at week 16 was also significantly higher in the CBP-201 group than in the placebo group (-38.
1 versus -12.
3 percent, see Figure 3).

Figure 2.
Proportion of subjects achieving EASI-50, -75 and -90 at week 16 (CBP-201 versus placebo, *** representing P<0.
001)

Figure 2.
The proportion of subjects with EASI-50, -75 and -90 was reached at week 16

Figure 3.
Peak pruritus numerical assessment scale at week 16 (CBP-201 versus placebo, ***, **, *representing P<0.
001, <0.
01, <0.
05, respectively)

Figure 3.
Week 16 peak pruritus numerical assessment scale

In terms of safety, CBP-201 is generally comparable to placebo, with the vast majority of treatment-related adverse events (TEAEs) being mild to moderate, and the incidence of serious adverse events (SAEs) in the treatment group and placebo group being 0.
6% and 3.
5%, respectively, with the same good safety profile
as similar drugs already on the market.

In summary, with excellent efficacy and safety data, CBP-201 is comparable to the world's first dupilumab (trade name: daptoxal ®), which targets IL-4Rα, in terms of treatment effect of AD, and even performs better in some data
.

In summary, with excellent efficacy and safety data, CBP-201 is not inferior to the world's first dupilumab targeting IL-4Rα, and even performs better in some data
than the world's first dupilumab targeting IL-4Rα.

AD is a very common chronic inflammatory skin disease, dry skin, rash, severe itching and other symptoms plague nearly 400 million patients worldwide, and there are nearly 70 million AD patients in China alone (Frost & Sullivan predicts).

The Chinese Guidelines for the Diagnosis and Treatment of Atopic Dermatitis (2020 Edition) (hereinafter referred to as the guidelines) point out that "the treatment of AD is to relieve or eliminate clinical symptoms, eliminate predisposing and/or aggravating factors, and reduce and prevent recurrence"
.

At present, AD treatment drugs can be divided into topical drugs and systemic (systemic) drugs, but external preparations are very inconvenient in the application of large lesions, and systemic adverse reactions
may also occur due to excessive drug exposure.

In fact, the choice of systemic drugs is limited in both type and clinical effect, and the guidelines suggest that first-generation oral antihistamines have negative effects on sleep and learning cognition, especially not recommended for children; Long-term use of immunosuppressants such as cyclosporine requires regular monitoring of a number of physiological indicators and close attention to adverse reactions; Corticosteroids are considered to be used as little or as little as
possible.

With the increasing cognition of immune inflammatory pathways, new targeted preparations have developed rapidly
in recent years.
Dupilumab, which is used for the treatment of moderate to severe AD, has been included in the list of clinically urgent drugs that have been marketed overseas by the NMPA/CDE, less than 6 months
from submission for approval to formal approval.
To a certain extent, this reflects the lack of new and effective AD treatment drugs in China, and also reflects the strong support of regulatory authorities for the research and development and declaration of related drugs, in order to enable the majority of AD patients in China to use better innovative drugs
faster.

Dupilumab has verified the reliability of similar drugs since its entry into China in 2020 and is expected to be extended to more indications
.
As a domestic new drug, CBP-201 has the efficacy and safety of dupilumab, which will significantly improve the accessibility of such drugs in the future and benefit more patients
.
If CBP-201 can achieve significant Q4W effects in the future, it will be administered every 4 weeks, which will bring great convenience
to patients, especially moderate to severe adolescents and children, and their families.

As a domestic new drug, CBP-201 has the efficacy and safety of dupilumab, which will significantly improve the accessibility of such drugs in the future and benefit more patients
.
If CBP-201 can achieve significant Q4W effects in the future, it will be administered every 4 weeks, which will bring great convenience
to patients, especially moderate to severe adolescents and children, and their families.

The development of CBP-201 has not been easy
.
International Phase IIb clinical data released at the end of 2021 sparked polarization in market evaluations, and although the study met preset primary and secondary endpoints, it caused controversy in some specific data, resulting in poor
stock price performance.
However, Conrad insists on scientific and objective analysis of results and actively conducts follow-up trials, strictly implementing high-level clinical research
.

However, Conrad insists on scientific and objective analysis of results and actively conducts follow-up trials, strictly implementing high-level clinical research
.

Yaodu has discussed the data of the phase IIb clinical study of CBP-201, the original link is as follows: Challenge the best - China's biotech goes international, series of reports (I), the article pointed out that the baseline of Chinese subgroup patients is closer to the clinical study of dupilumab, while foreign subjects are lighter in AD severity, BMI is also larger, and the response rate is not as good as that of Chinese subgroup patients.
This led to the impression
that the overall efficacy data for CBP-201 in this phase II b study may not look as good as dupilumab.

Challenge the best - China's biotech goes international, series of reports (1)

Figure 4.
Post-hoc analysis of CBP-201 in phase IIb clinical study (*P<0.
05, **P<0.
01, ***P<0.
001 vs="" baseline="" easi="" tertiles:="" low:="" mid:=""">18.
4 and ≤26.
4, High: >26.
4Baseline TARC tertiles: Low: ≤ 116 pg/mL, Mid: >116 pg/mL and ≤291 pg/mL, High: >291 pg/mL)

Figure 4.
Post-hoc analysis of CBP-201 in a Phase IIb clinical study

In fact, shortly after the data was released, international first-line investment banks Jefferies, Piper Sandler and SVB Leerink successively published articles to objectively and comprehensively evaluate the data performance of CBP-201 and give affirmation, Bruce Strober (clinical professor of dermatology, Yale University School of Medicine) and Jonathan I.
Silverberg (professor of dermatology at George Washington University's School of Medicine and Health Sciences) and others also expressed positive approval
of the CBP-201 data and progress.

Subsequently, Conrad adhered to scientific and objective analysis of results and actively carried out follow-up trials, strictly implementing high-level clinical research
.
The population and results of this key clinical trial are basically consistent with the results of the last phase IIb China subgroup (n=32), reflecting the continuity and trend, and the change range of IGA and EASI, the main indicators of 300mg Q2W, is similar.

1.
Strober, B et al.
Abstract and Poster Accepted.
Maui Derm2022 Figure 5.
Previously released phase IIb Chinese subgroup data (the main index IGA0-1, EASI change amplitude is obvious, but also suggests that Q4W administration and Q2W have the potential for the same good efficacy)

Figure 5.
Previously published phase IIb China subgroup data

The disclosure of the latest clinical data has provided a satisfactory answer sheet for friends from all walks of life who pay attention to the project, and the results of this time further confirm the previous post-hoc analysis, reflecting the prudent and objective scientific research spirit
.

Autoimmune diseases have a large patient population, but it is not an exaggeration
to say that you want to run well on this track.
The screening of subjects alone needs to consider issues affecting the baseline level, such as disease severity, years of illness, and racial differences, and complex self-immunity symptoms bring challenges
to clinical endpoint selection.

The pivotal clinical study of CBP-201 is based on the previous clinical 1b study conducted in Australia and New Zealand and the international multicenter clinical 2b study conducted in the United States, Australia, New Zealand and China, which can theoretically support the listing
of CBP-201 in China.

CBP-201, a pivotal clinical study in China, also coincided with frequent outbreaks, which presumably also caused some obstacles
to the smooth administration and follow-up of clinical studies.
We also note that Conrad has conducted the most conservative processing and statistical analysis of clinical data using the J2R (Jump to reference) method in accordance with the latest ICH E9(R1) principle, and still obtained positive results with high confidence, which undoubtedly further verifies the technical level and clinical research quality
of the CBP-201 program.

This undoubtedly further verifies the technical level and clinical research quality
of the CBP-201 project.

It is worth mentioning that this project has completed the largest clinical study of atopic dermatitis biological products in China so far, and according to public information, the cumulative number of patients in clinical studies of CBP-201 products worldwide has exceeded 800.

This pivotal clinical trial not only provides strong data support for the listing of CBP-201, but also plays a good demonstration role
in domestic AD-related clinical research.

The data obtained at this stage is exciting, but we can also find from the newly released data that the curve of CBP-201 improvement in AD symptoms did not peak at week 16 (see Figure 1 above), and its efficacy response data curve still showed a clear upward trend, which is likely to mean that the efficacy of CBP-201 will be further highlighted and more expected
as follow-up trials are carried out.

In addition, data from the previous CBP-201 international phase 2 study suggest that the Q4W dosing regimen also showed significant improvements
in skin clearance, disease severity and pruritus.

The ongoing Phase II study to evaluate the long-term efficacy of CBP-201, including the continuation of the current bi-weekly dosing regimen (Q2W) and the more convenient quadrennial dosing regimen (Q4W), is also highly anticipated and is expected to further improve medication adherence in AD patients
.
The optimization of the frequency of administration is one of the important unmet needs for the treatment of AD, and it is also the currently unapproved dosing frequency
of dupilumab for AD patients.

Based on the company's press release, Conrad is expected to actively seek to communicate with CDE in the coming months to discuss how to successfully bring the product to market as quickly as possible
.

CBP-201, as one of the top three or even me-better products in the domestic market, has great
market potential in the future.
Compared with major international competitors, its key data also belongs to the first echelon (see figure below).

Figure 6.
CBP-201 versus mainstream drugs (non-head-to-head trial)

Dupilumab's global sales reached US$6 billion in 2021, and since its launch in China in June 2020, its domestic market sales in 2021 have reached nearly RMB320 million (Yaodu sales data), with broad
market prospects.

Figure 7.
Dupilumab worldwide sales data (US$ million)

Reference degree primumab has achieved excellent sales performance in both the world and China, which also plays a role in paving the way for the future commercialization of CBP-201
.

CBP-201 will be recognized by more doctors and patients with solid clinical data, and even explore unique differentiating values (such as possible adherence improvement).

At present, the transaction value of AD-related targeted new drug rights in China can reach hundreds of millions of US dollars, and the commercial value of the CBP-201 project will continue to increase
as more clinical data accumulates.

brief summary

In order to achieve the world-class level, from drug R&D design to clinical research to commercialization, they are facing higher requirements and challenges, and innovative drug companies need to forge ahead and constantly transform
.

Leading biotech, represented by Conrad, has made active efforts to catch up with the international leading level, and is not afraid of occasional storms and rains.

With independent innovative R&D platform technology and excellent product strength, Conrad is in line with international standards in registration application and clinical development, and gradually realizes the internationalization of Biotech, which vividly reflects the development trend
from challenge the best to be the best.

Resources:

References: References:

1、CBP-201 China Interim Data Release -Oct.
4 2022

2、Connect Biopharma - Corporate Presentation - October 2022

3.
"Challenge the best-Chinese pharmaceutical companies challenge the international first-line series" Based on the in-depth interpretation of the research reports of foreign professional institutions

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