Top 10 Pharma Industry Updates: Seven Blockbuster Drugs Facing Patent Expiry in Next Five Years and More

A Total of 10 Brief News Items | Estimated Reading Time: 6 Minutes◆◆ ◆

Industry Observation

1｜In the next 5 years, core patents of 7 blockbuster drugs worth billions will expire

Small molecule drugs, as the most commonly used type of medication in clinical practice, also have the widest impact after their patent expiration.Approximately 130 core patents for small-molecule chemical drugs will expire in the next five years.This article reviews seven blockbuster drugs with global sales of billions of yuan, providing reference for corporate R&D project initiation.

Table 1: Seven Billion-Dollar Small Molecule Drugs with Core Patents Expiring in the Next Five Years

Data Source: PharmCube Data, PharmCube Consulting

2｜Sanofi Announces "All in" Artificial Intelligence

On June 13, Sanofi announced the next step in its company-wide digital transformation, going "All in" on artificial intelligence and data science to accelerate breakthrough achievements for patients.

This might be the first multinational pharmaceutical giant to make such a bold statement under the AI wave, representing Sanofi's full commitment to AI. Chief Executive Officer Paul Hudson stated: "Our goal is to become the first pharmaceutical company driven by artificial intelligence on a large scale, providing our employees with tools and technologies focused on insights, enabling them to make better daily decisions. We have only scratched the surface of how we adopt these disruptive technologies to achieve our ambition of transforming medical practice." Unlike previous collaborations with AI companies, this time Sanofi is serious. (Source: PharmaAI)

3｜Stock Price Surges Over 240% in 40 Days, Has the ADC Pioneer Made a Comeback?

At the 2023 ASCO, Immunogen's FRαADC (Elahere) achieved a "home run" in its pivotal Phase III clinical trial, erasing the shame of a previous Phase III failure and, outside the shadow of DS-8201, opened up yet another "first-place game."

On May 3, the company announced positive pivotal data from the Phase III MIRASOL trial for Elahere, potentially leading to the world’s first new drug extending overall survival (OS) in platinum-resistant ovarian cancer patients. Additionally, a supplemental Biologics License Application is planned for submission in the U.S. in the second half of this year. Following the announcement, ImmunoGen's stock price surged 136% on the same day, and from May 3 to June 13, ImmunoGen's stock skyrocketed approximately 242.5% over 42 days. (Source: E Pharma Manager)

4｜The first Chinese large molecule drug to go overseas may not be PD-1.

On June 8, Yifan Pharmaceutical announced on the investor interaction platform that the U.S. FDA conducted a pre-approval inspection of the original liquid production site of Beijing Yifan, a holding subsidiary of Yifan Pharmaceutical, for the marketing application of its efgartigimod alfa injection (hereinafter referred to as "Yilishu"), which was successfully completed on June 7.

Yifan Pharmaceutical stated that the "Form 483" issued by the US FDA inspector involves matters that need to be rectified, all of which are relatively easy to resolve or correct, and a response is planned to be submitted to the FDA within 15 working days.

If this innovative drug successfully passes the FDA and European EMA (European Medicines Agency) on-site review and achieves market launch, Yifan Pharmaceutical will become the first Chinese company to simultaneously launch a large-molecule innovative biologic drug in China, the U.S., and Europe. (Source: Medical Investment Tribe)

5｜How Many "Dark Horses" Are Expected to Cross the Finish Line in China's 2023 National Healthcare Negotiations?

With the release of last week's adjustment plan for the medical insurance catalog, preparations for the 2023 National Reimbursement Drug List (NRDL) negotiations have been put on the agenda. In addition to the newly approved drugs that have already qualified for the "preliminary round," the deadline of June 30 has naturally become one of the focal points in the industry. New drugs that are approved by the end of this month will also have the opportunity to secure a valuable spot in the NRDL negotiations.

Which new drugs are expected to make a successful push and become the dark horses entering the national negotiation?

1. Third-generation EGFR-TKIs: Ruizetinib, Limertinib, and Aoruitinib. Following the first-tier third-generation EGFR-TKIs Osimertinib, Aumolertinib, and Furmonertinib, four second-tier companies in China successively submitted applications for marketing in 2021. Now, it seems to be the harvest season. Beida Pharmaceutical's "Befutinib" was just approved for marketing on May 31, coinciding with favorable national negotiation conditions, and is expected to enter the medical insurance system in the same year of its market launch. According to the Insight database, the review progress of the three closely following drugs is now nearing completion, with a similarly promising chance of rapid approval and inclusion in the medical insurance competition. These include Ruizetinib from Shijiazhuang Pharmaceutical Group/BerGenBio, Limertinib from Aosaikang Pharmaceutical, and Aoruitinib from Sunho Pharmaceutical. If all these drugs successfully make it onto the last train, there will be a fierce competition among seven third-generation EGFR-TKIs in the medical insurance negotiations.

2. ALK Inhibitors: Qilu Pharmaceutical vs. Zhengda Tianqing. For ALK inhibitors, three new drugs applied for marketing approval in 2021-2022 are close to the approval stage: Qilu Pharmaceutical's Ilunacek, and Zhengda Tianqing's Efunacl and TQ-B3101 (Unecritinib). Particularly, Ilunacek has already exited the second round of supplementary data queue.

3. PD-L1 Monoclonal Antibodies: Kelun Pharmaceuticals, Hengrui Medicine, and Lee's Pharmaceutical. In China, although the competition for PD-L1 is not as intense as that for PD-1, it has gradually entered a period of rapid growth since 2021. In a short time, the first-tier Envonli monoclonal antibody and Sugemalimab were successively approved. Following closely, Lee's Pharmaceutical’s ZK001, Kelun Pharmaceutical’s Teltilimab, and Hengrui Medicine’s Adebrelimab have all been submitted for market approval. At the beginning of 2023, Chia Tai Tianqing also submitted an application for TQB2450. Among these new drugs, Hengrui, which reported production in early 2022, has taken the lead and was the first to be approved in February 2023; Kelun and Lee's Pharmaceutical are also close to approval based on the review progress of their acceptance numbers. (Source: Insight Database)

Industry News

6｜Liver Fat Reduced by Over 70%! Positive Phase 2 Clinical Results for GLP-1 in Treating Non-Alcoholic Fatty Liver Disease

Recently, MSD announced that it will present the phase 2a clinical trial results of its investigational GLP-1/glucagon receptor dual agonist efinopegdutide for the treatment of non-alcoholic fatty liver disease (NAFLD) at the European Association for the Study of the Liver (EASL) annual meeting. The conference abstract shows that efinopegdutide significantly reduced liver fat levels in patients compared to an active GLP-1 agonist control. After 24 weeks, liver fat levels decreased by 72.7% in the efinopegdutide group, compared to 42.3% in the active control group.

In this clinical trial, 145 patients were randomly assigned to receive either efinopegdutide (10 mg once weekly) or semaglutide (1 mg once weekly). The trial results showed that after 24 weeks, liver fat levels in the efinopegdutide group decreased by 72.7% (95% CI: 66.8, 78.7), compared to 42.3% (95% CI: 36.5, 48.1) in the active control group. In terms of weight loss, after 24 weeks, the efinopegdutide group experienced an average weight reduction of 8.5%, while the active control group had a 7.1% reduction (p=0.085).

Merck announced that efinopegdutide has recently been granted Fast Track designation by the U.S. FDA for the treatment of NASH patients. The company stated that these data support advancing efinopegdutide into Phase 2b clinical development. (Source: WuXi AppTec)

7｜Breakthrough in Stroke Medication! These Four Types of Patients Can Also Achieve "Excellent Clinical Outcomes"

Recently, the international top medical journal "The New England Journal of Medicine" (NEJM) published the analysis results of the RESCUE BT2 trial conducted by the team of Professors Yang Qingwu and Zi Wenjie from the Second Affiliated Hospital (Xinqiao Hospital) of Army Medical University. The study shows that intravenous infusion of tirofiban for 48 hours combined with oral aspirin for 90 days can significantly improve clinical outcomes in patients with moderate or severe stroke (without large/medium-sized cerebral artery occlusion). (Source: WuXi AppTec)

8｜Discovery of New Target! Zhejiang University Scholars Make Significant Theoretical Breakthrough in Relapsed and Refractory Leukemia Research

On May 22, 2023, Professor Meidan Ying from the College of Pharmaceutical Sciences at Zhejiang University, as the corresponding author, published a research paper titled "Palmitoyltransferase ZDHHC21 regulates oxidative phosphorylation to induce differentiation block and stemness in AML" in Blood, a top international academic journal in the field of hematology. This study identified for the first time that palmitoyltransferase ZDHHC21 is a key factor in regulating the abnormal activation of OXPHOS in AML cells, particularly LSC cells. It elucidated the novel biological role of ZDHHC21 in inducing differentiation block and promoting stemness potential in leukemia cells by activating OXPHOS. The study proposed inhibiting ZDHHC21 as a potential therapeutic strategy for AML patients, especially those with relapsed/refractory conditions, providing new drug targets and approaches for the clinical treatment of leukemia.

In this study, to identify the key mechanism of OXPHOS abnormal activation in AML cells, researchers screened a library of post-translational modification enzyme inhibitors and found that palmitoyltransferase (ZDHHC) inhibitors significantly suppressed OXPHOS activity in AML cells. Further screening using siRNAs targeting 23 ZDHHC proteins revealed that ZDHHC21 selectively regulates OXPHOS activity in AML cells. Subsequent findings showed that ZDHHC21, which is specifically highly expressed in AML, leads to differentiation block, enhanced stemness, and chemotherapy resistance in AML cells. Inhibition of ZDHHC21 selectively reduces OXPHOS activity in AML cells, thereby inducing myeloid differentiation of AML cells and weakening the stemness potential of LSCs. Further mechanistic studies revealed that ZDHHC21 promotes malignant progression of AML in an enzyme activity-dependent manner by specifically catalyzing the palmitoylation of AK2, promoting its mitochondrial localization and thus activating OXPHOS. Finally, targeted intervention of ZDHHC21 effectively inhibits the growth of AML cells at the whole-animal level and significantly prolongs the survival time of leukemia mice transplanted with cell lines and patient-derived cells. More importantly, inhibition of ZDHHC21 can effectively eliminate leukemia cells derived from relapsed/refractory AML patients in PDX models and significantly enhance their sensitivity to first-line chemotherapeutic drugs, providing a novel strategy for clinical treatment of relapsed/refractory AML patients.

The discovery of new intervenable targets for anti-tumor treatment and the development of innovative drugs have always been the main research focus of Professor Yang Bo and He Qiaojun's team from the School of Pharmacy. Professor Ying Meidan is the primary pioneer in the team’s focus on pediatric tumors and hematological diseases. This paper is the second research article published by the team in *Blood*, reflecting the team's sustained innovation capability in this field. The paper was co-first-authored by Researcher Shao Xuejing and Ph.D. student Xu Aixiao from the School of Pharmacy at Zhejiang University. This work was supported by projects including the National Natural Science Foundation of China, the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars, and the Zhejiang Provincial Natural Science Foundation. (Source: Bioon)

Policy Brief

9｜Official Update to the "Directory of Health Claims for Health Foods"

Recently, the State Administration for Market Regulation, the National Health Commission, and the National Administration of Traditional Chinese Medicine have released the "Directory of Health Functions Allowed to be Claimed by Health Foods - Nutrient Supplements (2023 Edition)."

Among them, the interpretation of health functions is labeled according to the content in Appendix D of the current "National Food Safety Standard - Nutrition Labeling for Prepackaged Foods" (GB28050); health food labels may use one or more of the corresponding standard claims regarding nutrient function from the interpretation. The functional claim language must not be altered, added to, or merged in any form. (Source: State Administration for Market Regulation)

Industry Regulation

10｜A Batch of Medical Devices Voluntarily Recalled

1. Boston Scientific International Medical Trading (Shanghai) Co., Ltd. reported that due to one implantable cardiac pacemaker being incorrectly distributed to a customer in Italy, the pacemaker division of Boston Scientific Corporation initiated a voluntary recall of the implantable cardiac pacemaker (China Medical Device Registration No. 20183120509). The recall level is classified as a Level III recall.

2. Bard Medical Technology (Shanghai) Co., Ltd. reported that due to the inner diameter and length of specific batches of coaxial cannulas exceeding the outer diameter and length of biopsy needles, the biopsy needles could not be properly inserted into the coaxial cannulas and reach the target tissue. The manufacturer, Bard Peripheral Vascular, Inc., voluntarily recalled the disposable guiding biopsy needle Bard® Mission® Disposable Core Biopsy Instrument Kit (China Medical Device Registration No. 20212140255). The recall level is classified as a Level Three recall.

3. FUJIFILM (China) Investment Co., Ltd. reported that due to the possibility of the mechanical arm, which connects and secures the tube, breaking under certain conditions in specific batches, and when the light radiation field is set near the maximum value, the deviation of the X-ray radiation field may not meet the requirements of the IEC60601-2-54 standard. FUJIFILM Corporation, the manufacturer, voluntarily recalled the digital mobile radiography X-ray system 移動型デジタル式汎用一体型X線診断装置 (Registration No. 20222060327 for Imported Medical Devices in China). The recall level is Class II.

4. Cepheid (Shanghai) Trading Co., Ltd. reported that due to the discovery of expired pipettes with specific batch numbers before the expiration date of the kit, the manufacturer, Cepheid AB from Sweden, initiated a recall for the Chlamydia trachomatis (CT)/Neisseria gonorrhoeae (NG) nucleic acid detection kit (multiplex real-time fluorescent PCR method), Xpert CT/NG Assay (Imported Medical Device Registration No. 20203400008). The recall level is classified as a Level Three recall.

5. MicroPort Scientific Corporation reported that MicroPort Orthopedics, Inc., the manufacturer, initiated a Level II recall of hip joint femoral heads (Registration No. 20153131977) due to incorrect information on some product labels.

6. Johnson & Johnson (Shanghai) Medical Devices Co., Ltd. reported that due to overseas complaints, it was observed that when the disposable OCTARAY Mapping Catheter with TRUEref Technology was used together with an ablation catheter, blood coagulum was found adhering to the electrodes and branches. The manufacturer, Biosense Webster, Inc., initiated a Level III recall for the disposable OCTARAY Mapping Catheter with TRUEref Technology (Registration No.: 20233070056). (Source: National Medical Products Administration)