R&D's 2022: Mo Dao's floating clouds end the day, and the harsh winter has bloomed spring buds

Wu Yilong: NSCLC brews new breakthroughs in clinical research

Professor Wu Yilong, Vice President of Guangdong Provincial People's Hospital and Director of Guangdong Institute of Lung Cancer

Looking back at the progress of lung cancer (mainly taking non-small cell lung cancer as an example, NSCLC) in 2022, it is not easy
to make more breakthroughs under the new crown epidemic and the "cold winter" of the industry.
Among them, there are many wonderful performances of Chinese scholars and local innovative drugs, but at the same time, we can see that our drug research design is still mainly Me-too, lack of innovative research design, and local innovative drug companies still need to work hard
.

Among these studies, some of them are blockbuster studies that change clinical practice and overcome existing drug resistance mechanisms, whether they are early or late trials, which are worth looking forward to; There are some clinical studies that are brewing new breakthroughs, for example, neoadjuvant immunotherapy is conducting a number of single-agent and combination studies with good
prospects.
Targeted drugs and immunotherapy continue to become clinically valuable treatment methods
in the field of lung cancer.
In addition, the clinical value of ADC drugs in patients with advanced NSCLC should not be underestimated
.
For example, in August 2022, Enhertu (DS-8201) was approved by the FDA for the treatment of unresectable or metastatic NSCLC carrying activated HER2 mutations, ushering in the first ADC
for lung cancer treatment.

In the field of targeted drugs, some old targets such as EGFR, ALK, ROS1, BRAF, cMET continue to emerge new drugs, while new targets such as RET, MET, KRAS, TIGIT new drugs have also emerged, for locally advanced NSCLC, sequential radiotherapy after chemotherapy can reduce disease recurrence, and new chemotherapy drugs are also worth looking forward to
.

In the field of immunotherapy, immune checkpoint inhibitors are showing the dawn of treatment with driver gene-positive NSCLC
.
At the same time, immunotherapy is developing towards early application, and drugs based on the synergistic complementary mechanism and excellent clinical data of dual immunotherapy have also been approved by the FDA and the State Food and Drug Administration for lung cancer treatment, and dual immunotherapy has shown good efficacy
.

In recent years, the medical community has proposed "value-based medicine", that is, selecting appropriate drugs and treatments
for patients according to their therapeutic value.
To this end, the China Thoracic Cancer Research Collaboration (CTONG) has also developed a scoring standard on value-based care in an attempt to maximize
the benefits for patients.
In clinical practice, patient-centeredness requires a comprehensive assessment of the patient and the selection of an individualized treatment model
.
This is also consistent
with a series of technical guidelines for the design, risk assessment and implementation of patient-centered clinical trial protocols issued by the Center for Drug Evaluation of the State Food and Drug Administration last year.

Looking forward to the New Year, thousands of sails pass by the side of the sinking boat, and ten thousand wood springs
in front of the sick tree.
I sincerely wish everyone a safe and healthy life, and hope that other cancers such as lung cancer can be cured or become chronic diseases forever
.

Li Haiyan: The improvement of clinical research capabilities is an eternal theme

Professor Li Haiyan, Director of Drug Clinical Trial Institute, Peking University Third Hospital

After China joined ICH in 2017, drug research and development has become increasingly globalized, which not only helps to accelerate the launch of innovative drugs in China, so that Chinese patients can benefit from global innovation achievements as soon as possible, but also enables Chinese local innovative drugs to go abroad as soon as possible and benefit a wider range of global patients
.

One of the key links to achieve global R&D is that Chinese research centers need to have an international vision, modern technology and commercial operations in order to participate in global early-stage clinical research earlier, control the risks of early-stage clinical research, and simultaneously carry out global key phase III.
clinical trials
.

The improvement of clinical research capabilities and the cultivation of various professional talents are the eternal themes in the industry, and on the occasion of 2023, we look forward to all parties in the industry working together to create a win-win ecological environment for new drug clinical research and development, and help China's new drug research and development develop healthily and vigorously
.

Zhang Jian: The persistence and luminosity of breast cancer drug research and development

Professor Zhang Jian, Executive Deputy Director of Department of Medical Oncology/Medical Director of Phase I Clinical Research Ward, Fudan University Cancer Hospital

2022 is destined to be an extraordinary year, ice and fire, laughter and tears, salary, perseverance, and luminosity, which is not only a true portrayal of the epidemic, but also a true portrayal
of breast cancer workers and Chinese new drug developers.

In 2022, in the global field of breast cancer research, we saw a full-scale outbreak of ADC drugs, and DB04 broke the sky, abruptly pulled out the therapeutic subgroup of HER2 low expression, and played a new symphony of destiny; DB03 lived up to expectations and cleanly grabbed the second-tier gold throne of HER2-positive breast cancer; TROPiCS02 made a hot appearance, and the intervention space
for SG in refractory ER-positive breast cancer was set aside outside the triple negative.
In 2022, we also saw the field of endocrinology step by step, AKT inhibitor Capivasertib once again demonstrated the characteristics of doubling PFS in endocrine therapy without relying on pathway abnormalities; CDK4/6i directly challenges the taboo area of visceral crisis to find Right Choice; The continued benefits of abecilide-assisted have finally landed; Oral SERD drugs are a few joys and several sorrows
.

In 2022, the original research strength of domestic breast cancer will also accumulate: the three-negative Fudan classification and tumor ecology theory will be widely recognized; Some names (SHR-A1811, ARX788, A166, DX126-262, DB1303, BL-M07D1, SKB264, Dalsili) have been remembered, and a series of landmark events have been born, and self-research and cooperation are intertwined
.
The CDK4/6i of Guochuang finally saw the light of day and the first light (DAWNA); The new TKI pyrotinib challenges the status of HER2-positive new auxiliary and first-line classic double antibody for the first time, and has achieved a small victory, which still needs to be come
.

In 2022, new targets and new hopes, HER3, EGFR, B7-H3, B7-H4, FRα, Nectin-4, and TF will become hot spots in the future; In 2022, new strategies and new prospects, all kinds of bispecific antibodies, bispecific ADCs, PROTAC technologies, and cell therapy bring unlimited possibilities
.

In 2022, concepts such as "patient-centered" and "net benefit" have been raised to a higher height, reflecting the industry's concern for cancer patients, and it is also a real feedback on the urgent need for individualized and dynamic treatment, which will surely become an eternal topic
in the future.

"Leaving the old and welcoming the new", it seems that the word has a deeper and farther meaning
when 2023 arrives.
Go to the pain, the end of the epidemic, thousands of families pupil day, always replace the new peach with the old charm
.
I also sincerely wish everyone, in 2023, to take the helm of dreams again and continue to fly with dreams
.

We believe in our future, not because the future is worth believing, but because the future must be believed
.

Zhao Chongbo: The treatment pattern of myasthenia gravis will change in 2022

Professor Zhao Chongbo, Chief Physician, Department of Neurology, Huashan Hospital, Fudan University

2022 is destined to be an extraordinary year, from the "strict prevention" of the new crown epidemic to "optimization and release", which has affected the life and work
of each of us to varying degrees.
However, human scientific progress and cognitive iteration will not stop, time does not wait, development is still the main theme
that penetrates our time and space.

As a classic neuroimmune disease, the treatment pattern of myasthenia gravis will further change
in 2022.
Our understanding of myasthenia gravis has evolved from "antibody disease" in a narrow sense to "immune network disease"
in a broad sense.
Therefore, targeted therapy for the core links in disease immunopathology is the focus of current therapeutic exploration, and important progress
has been made in many aspects.

Pathogenic antibodies and complement activation are the core pathological links in the autoimmune effector stage of myasthenia gravis, and FcRn antagonists that promote endogenous clearance of pathogenic antibodies by targeting neonatal Fc receptors (FcRns) will perform prominently
in 2022.
Efgartigimod was approved by the U.
S.
Food and Drug Administration in December 2021 and approved for marketing in Japan this year, and interim results were published this year in the 3-year ADAPT Expansion Study (ADAPT+), showing that long-term use of efgartigimod is effective and safe
。 Rozanolixizumab completed the global multicenter phase III clinical trial (MycarinG) with positive results, bartolimab completed the phase II multicenter clinical trial in China and published its positive results, and the global multicenter phase III clinical trial of Nipocalimab was initiated
in China.
The Ravulizumab study targeting complement C5 (CHAMPION MG) has published the results of the open-label extended phase interim study that can continue to improve clinical scores in patients with myasthenia gravis with a good
safety profile.
Zilucoplan has also completed a global multi-center Phase III clinical trial with encouraging results
.

More importantly, myasthenia gravis has entered the era of true evidence-based medicine from the era of "good good clinical practice points (GPP)" in the past, driven by multiple global multi-center new drug registration trials, high-level clinical research has emerged one after another, which is amazing in terms of clinical problem focus, research design and research results, and will have a profound impact
on the diagnosis and treatment practice of myasthenia gravis.

"Patient-centered" is the most basic responsibility of doctors and the basic criterion
for clinical medical introduction.
The pattern of our relationship with patients can be summarized as "RELIEF", R-respect stands for respect, E-education stands for educating patients, and L-leading stands for guiding patients
.
Among them, I-inform, E-empathy (empathy) are important, which are important cornerstones
that connect the good relationship between our doctors and patients.

Shakespeare said, "All the past is a prologue!" " I sincerely wish everyone not to dwell on the past, worry about the future, focus on the present in the new year, and embrace a better self
.

Cao Ye: The "gatekeeper" of the clinical trial industry is moving forward

Dr.
Cao Ye, Deputy Director of Clinical Research Department/Office of Drug Clinical Trial Institution, Cancer Center of Sun Yat-sen University

Over the past three years, the clinical trial industry has experienced unprecedented challenges! The epidemic has made our lives and work through many uncertainties and adjustments, but we still keep our original intention and forge ahead in the GCP industry we love
.

If you open the official website of the State Food and Drug Administration, you will be moved by the "gatekeeper" of the clinical trial industry in 2022, still full of work status, still dedicated and practical work attitude
.
In 2022, the NMPA issued a total of 3 departmental rules and 10 administrative normative documents; The Center for Drug Evaluation issued 60 technical guidelines for drugs and 10 notices for the promotion of ICH guidelines; The Drug Review and Inspection Center issued 9 drug-related policy notices and 7 medical device-related policy notices, and the on-site verification of clinical trial data was carried out "in small steps and without stopping".
.
.

As a Guangdong GCP practitioner, like many colleagues in China, we strive to minimize the impact of the epidemic on normal clinical trial work, strive to strike a balance between anti-epidemic and clinical trial development, strive to create a safer test environment for subjects, and strive to work together with partners to overcome difficulties! In 2022, Guangdong GCP people cohesively wrote and released 2 "Guangdong Consensus"; Take advantage of online live broadcast to hold 12 public welfare clinical research salons; With the help of Guangdong GCP expert resources, 12 third-party evaluations of drug clinical trial institutions were carried out; Relying on the "Research and Learning Exchange" of Guangdong Cancer Trial Alliance, 6 online CDE guiding principles learning and exchange were organized; Give full play to the vitality of young GCP people, organize the Guangdong GCP Youth Forum Phase 2 and the Drug Administrator Training Phase 1; Invited by various institutions in the province, the GCP training of "teachers at home" is even more popular, and a large number of medical staff who are interested in joining the clinical trial family have been trained.
.
.

When we stand at the end of 2022 and look back at the past, the times let us experience and fight in difficulties, we did not retreat but chose to move forward bravely, we deserve to toast ourselves and our colleagues! On the occasion of the arrival of 2023, we have seen the new trend of the industry, felt the new changes that the industry is about to usher in, always keep curious and optimistic, and we will continue to be the trendsetters and keepers of the industry!

Xu Chongyuan: Ignite the heroism of hardship together, and join hands to start all over again

Professor Xu Chongyuan, Director of the National Drug Clinical Trial Institution Office and Director of the Drug Clinical Trial Center of Nanfang Hospital of Southern Medical University

Standing at the end of 2022, if summed up in one word, I think it can be the word
"difficult".
This year, everyone, every family, and everyone has all kinds of difficulties and difficulties in all aspects, and the suffering accumulated by the pandemic for three years has fully broken out in 2022, which cannot be counted, complained, or heard, and every family has difficult scriptures that are difficult to read, difficult to numb
.

The same is true
in the field of biomedical clinical research and development.
Once we had endless experimental projects, endless researchers' meetings, endless errands.
.
.

We miss the good times of the past, lament the good times of the past, hope that the dark night will pass as soon as possible, return to yesterday's glorious days, and even miss the shuttle between the airport and the high-speed train between cities, miss the coffee in the hotel lobby.
.
.

However, it is easier
said than done.
Three years of the pandemic, not only one or two, but more than one or twenty black swans
.
The disaster caused structural damage to many things, collapsed platforms, and the mud and sand after the disaster made the industry extremely difficult
.
In the short term, we need to adjust the original expectations and adjust the original pace, but I believe that the long-term improvement of the biomedical industry will not change, and the interruption of the epidemic is a good thing, giving us the opportunity to adjust, we can re-examine whether some of the original tracks will continue? Can we find a different way to differentiate ourselves in the present?

Of course, after a great disaster, post-disaster reconstruction is needed, and what is more needed is boldness and courage
.
It takes the courage to endure hardships and the courage
to start all over again.

Heroism is optimism to watch the flowers blossom and fall in front of the court, and it is also the intention to watch the clouds in the sky; Courage is the belief that life is desperate in difficult times, and it is also the strength
that time gives life tenacity and permanence.

The train of time does not stop, only moves forward
.
In the theme song of the TV series "The World", it is written: "The grass and trees will sprout, the children will grow up, the train of years, not for anyone to stop.
.
.
"

At any time, we need to move forward firmly, we need the friendship of destiny and common cooperation, the inseparability of being in the same boat through thick and thin, and the care and empathy
that reaches people's hearts.

Come in 2023 and rebuild together!

Shen Yifeng: CNS drug innovation technology improves R&D quality and efficiency

Professor Shen Yifeng, Director of the Institutional Office of Shanghai Mental Health Center

In 2022, the new crown epidemic is raging, and many cities have pressed the pause button
.
As a doctor, I support designated hospitals to diagnose and treat patients with mental illness infected with the new coronavirus; As a patient, I experienced a complete course of coronavirus infection; As a GCP practitioner, I deeply appreciate the practical significance
of pursuing good clinical practice with a sense of professional mission.

In the field of biomedical research and development, vaccines, drugs and medical devices are all important weapons
for maintaining health.
To let professional people do professional things, professionalism and long-term philosophy should be implemented - insisting on doing the right and difficult things
.
The concept of "patient-centric" has become the guide for innovation, so it requires in-depth needs research, full collection of patient experience data, and trial models that are more in line with patients' wishes
.

In the field of psychotropic drug research and development, long R&D cycles and high failure rates have deterred some sponsors
.
However, recent data show that China's new drug R&D pipeline has increased significantly, and breakthroughs are expected in multiple indications, especially the application of innovative technology to significantly improve quality and efficiency
.
A number of CNS innovation forums will be launched in 2023, and colleagues are welcome to participate and work together to improve human physical and mental feelings and quality of life
.

In the fight against viruses and many diseases, human beings may be temporarily inferior, but relying on the highly divided human civilization, we will eventually move forward
courageously.
Under the guidance of the spirit of the "20th National Congress of the Communist Party of China", we will make greater breakthroughs in deepening the implementation of the healthy China strategy and innovation-driven development strategy!

Patient organization