Pharma Frontiers: Daily Digest of Global Pharmaceutical News - May 29

1.Innovent Biologics' New Psoriasis Drug, Picankibart, Planned for Market Approval with Only 5-6 Injections Needed Annually

On May 28th, Innovent Biologics announced that their independently developed recombinant anti-interleukin-23p19 (IL-23p19) monoclonal antibody injection, Picankibart, achieved primary and all key secondary endpoints in the Phase 3 clinical study (CLEAR-1) conducted in China on patients with moderate-to-severe plaque psoriasis. In this study, the primary endpoint (16-week PASI90) exceeded 80%, and during the maintenance phase, Picankibart required only one injection every 12 weeks, with an anticipated annual dosage of only 5-6 injections. Innovent Biologics plans to submit a New Drug Application (NDA) to the National Medical Products Administration (NMPA) of China for the treatment of psoriasis with Picankibart.

Psoriasis is a chronic, relapsing, inflammatory systemic disease driven by genetic and environmental factors and mediated by the immune system, affecting individuals of all ages. Picankibart is a recombinant anti-IL-23p19 monoclonal antibody injection that specifically binds to the IL-23p19 subunit. By preventing IL-23 from binding to cell surface receptors, it blocks the IL-23 receptor-mediated signaling pathway, exerting anti-inflammatory effects. This holds promise for providing a more effective treatment option for patients with psoriasis and other autoimmune diseases.

The CLEAR-1 study that achieved primary and all key secondary endpoints is a multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical study, evaluating the efficacy and safety of Picankibart in patients with moderate-to-severe plaque psoriasis. The study demonstrated that Picankibart could sustain long-term and robust skin-cleaning effects within one year of treatment. By Week 52, the proportion of subjects achieving PASI 90 and sPGA 0/1 scores in the two dosage groups of Picankibart remained stable. At Week 52, the PASI 90 and sPGA 0/1 rates in the 200mg group were 84.9% and 85.9%, respectively. This provides strong clinical data supporting the efficacy benefits of long-term treatment with Picankibart for patients with moderate-to-severe plaque psoriasis.

2.Boan Biotechnology's Dulaglutide Injection Biosimilar Application Accepted by CDE

On May 28, Boan Biotechnology announced that its Biologics License Application (BLA) for the dulaglutide injection biosimilar (BA5101), independently developed by the company, has been accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) for the treatment of blood glucose control in adults with type 2 diabetes. BA5101 is a biosimilar to Dulaglutide, and its international registration and clinical trials are progressing simultaneously.

Dulaglutide is a long-acting GLP-1 (glucagon-like peptide-1) receptor agonist that is administered once a week. It can improve the function of pancreatic β-cells, and it stably and effectively lowers blood glucose and glycated hemoglobin (HbA1c) levels. Furthermore, its unique mechanism of action is less likely to cause hypoglycemia, and it can reduce body weight, blood lipids, and the risk of long-term cardiovascular diseases, also providing protective effects on the kidneys. Multiple clinical studies have shown that administering Dulaglutide once a week reduces the inconvenience of medication for patients and leads to higher medication adherence.

The original Dulaglutide product was developed by Eli Lilly and Company and has been approved in China for blood glucose control in adults with type 2 diabetes. According to a press release from Boan Biotechnology, the company has overcome several technical challenges related to the oxidation, breakage, and charge heterogeneity of Dulaglutide, efficiently advancing BA5101 from preclinical research to the clinical stage and completing phase 3 clinical trials.

The development of BA5101 strictly follows the research guidelines for biosimilars in China, the United States, the European Union, and other regions. It has met all study endpoints in two key clinical trials comparing it to the reference product. Phase 1 clinical trials confirmed that BA5101 has highly similar pharmacokinetic properties, safety, and immunogenicity to the original Dulaglutide. The relevant study results were published in the international academic journal Expert Opinion on Biological Therapy. Phase 3 clinical trials confirmed that BA5101 could quickly and stably lower blood glucose and glycated hemoglobin, with efficacy and safety consistent with the original Dulaglutide product.

3.Eisai/Biogen's Alzheimer's Antibody Drug Lecanemab Approved for Market in South Korea

On May 27, Eisai and Biogen announced that the Ministry of Food and Drug Safety (MFDS) of South Korea has approved the marketing of the humanized anti-soluble beta-amyloid (Aβ) monoclonal antibody lecanemab. This drug is indicated for the treatment of early (mild) Alzheimer's disease (AD) or mild cognitive impairment (MCI) due to Alzheimer's disease in adult patients. According to Eisai's press release, this marks the fourth country, following the United States, Japan, and China, where lecanemab has received approval.

Alzheimer's disease (AD) is a progressive, irreversible neurodegenerative brain disorder that leads to intellectual impairment, mental abnormalities, and the loss of social and functional capabilities, severely impacting patients' cognitive abilities and daily lives. It is estimated that in 2021, there were approximately 900,000 patients with dementia in South Korea, with one in ten people over the age of 65 having dementia and one in five having mild cognitive impairment (MCI).

Lecanemab can selectively bind to both soluble Aβ oligomers (protofibrils) and the insoluble Aβ polymers (fibrils) that make up Aβ plaques, thereby clearing Aβ protofibrils and Aβ plaques from the brain. Through this mechanism, lecanemab can slow disease progression and reduce the rate of cognitive and functional decline.

According to information disclosed by Eisai, lecanemab has met the primary endpoint and all key secondary endpoints in the large global Phase 3 study Clarity AD, with statistically significant results. The findings from the Clarity AD study have been published in the New England Journal of Medicine. The study data indicate that lecanemab exhibits significant efficacy and good safety. After three months of administration, it significantly reduced the Aβ load, and after 18 months, it effectively slowed disease progression by 27%. Additionally, 60% of earlier-stage patients experienced a reversal of disease course. These study results demonstrate that lecanemab can help early AD patients improve cognitive impairment and maintain their independence for a longer period, thereby reducing the socio-economic burden on families and society.

4.Sanofi's CD38 Antibody Receives FDA Priority Review for New Indication

On May 27, Sanofi announced that the FDA has accepted the supplemental Biologics License Application (sBLA) for its CD38 monoclonal antibody, Sarclisa (isatuximab), in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of newly diagnosed multiple myeloma (NDMM) patients who are ineligible for transplant. The FDA has also granted Priority Review for this new indication. If approved, Sarclisa will be the first CD38-targeting drug to be used in combination with the standard VRd regimen for such patients, marking the third indication for Sarclisa in the treatment of multiple myeloma. Last week, China's Center for Drug Evaluation (CDE) also accepted the marketing application for this indication of Sarclisa.

Sarclisa targets a specific epitope on the CD38 receptor expressed on multiple myeloma cells, triggering various mechanisms of action, including programmed tumor cell death (apoptosis) and modulation of the body's immune response. CD38 is highly expressed on multiple myeloma cells and serves as a surface receptor target for antibody therapies in multiple myeloma and other malignancies.

In December of last year, Sanofi announced that the IMROZ trial met its primary endpoint. The trial demonstrated that in newly diagnosed MM patients ineligible for transplant, Sarclisa combined with VRd significantly reduced the risk of disease progression or death compared to VRd alone. Sarclisa was first approved by the FDA in March 2020 for use in combination with pomalidomide and dexamethasone for adult patients with relapsed or refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. In March 2021, the FDA approved Sarclisa for an expanded indication, in combination with carfilzomib and dexamethasone for adult patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.

5.AstraZeneca Initiates Phase III Clinical Trial for Zibotentan/Dapagliflozin Combination Therapy in China for Chronic Kidney Disease

Recently, the Drug Clinical Trial Registration and Information Disclosure Platform revealed that AstraZeneca has registered a Phase III, randomized, multi-center, double-blind study in China for the combination therapy of Zibotentan and Dapagliflozin in the treatment of chronic kidney disease (CKD) with high proteinuria. The trial comprises two groups: the experimental group receiving the Zibotentan/Dapagliflozin combination therapy and the control group receiving Dapagliflozin monotherapy. The objective is to determine the efficacy of the combination therapy in reducing the estimated glomerular filtration rate (eGFR) over 24 months compared to Dapagliflozin monotherapy, in addition to standard of care (SoC).

Zibotentan is a highly selective endothelin A (ETA) receptor antagonist that can improve renal blood flow, reduce albuminuria, and alleviate vascular stiffness. However, studies have indicated that ETA receptor antagonists may cause high fluid retention rates. Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, can delay the progression of CKD in patients at risk. Additionally, Dapagliflozin helps expel fluid from the extravascular compartment, potentially further minimizing fluid retention risks.

In November last year, the Phase IIb ZENITH-CKD study of the Zibotentan/Dapagliflozin combination therapy in CKD patients with proteinuria demonstrated positive results, which were concurrently published in The Lancet. On October 18, the clinicaltrials.gov website listed the Phase III study (NCT06087835) of the Zibotentan/Dapagliflozin combination therapy in CKD patients with high proteinuria. The study aims to enroll 1,500 patients. AstraZeneca's registration of this trial on the China Drug Clinical Trial Registration and Information Disclosure Platform indicates the imminent commencement of the trial's China segment.

There are nearly 850 million CKD patients worldwide, with approximately 10% exhibiting high proteinuria. These patients face heightened cardiovascular mortality risks and a greater chance of progressing to renal failure, highlighting an urgent and unmet clinical need for effective treatments.

6.Daiichi Sankyo/AstraZeneca Initiates Domestic Phase III Clinical Trial for First-Line Treatment of EGFR-Mutant NSCLC

On May 27, according to the Clinical Trial Registration and Information Publicity Platform of CDE, Daiichi Sankyo/AstraZeneca registered and initiated a new Phase III clinical trial, TROPION-Lung14, on this platform. The study involves Dato-DXd (DS-1062a) in combination with Osimertinib for the first-line treatment of patients with EGFR mutation-positive locally advanced or metastatic NSCLC (Registration Number: CTR20241813). The primary endpoint is PFS as assessed by BICR, with secondary endpoints including ORR, DOR, and OS. The study was previously registered and initiated on ClinicalTrials.gov (Registration Number: NCT06350097). The domestic portion plans to enroll 174 participants, with an international target of 582 participants, and the first participant was enrolled on May 10. Previously, Dato-DXd had shown positive results in the treatment of EGFR-mutant NSCLC in later-line settings. The TROPION-Lung05 study targets advanced or metastatic NSCLC patients who have experienced disease progression during or after at least one tyrosine kinase inhibitor and at least one platinum-based chemotherapy regimen (with or without other systemic therapies). Data from this study presented at the 2023 ESMO Congress showed that among patients carrying EGFR mutations (n=78, the largest genomic mutation group), those treated with Dato-DXd had an ORR of 43.6%, DCR of 82.1%, mPFS of 5.8 months, and mDOR of 7.0 months. Data from the 2023 ESMO Asia Congress focusing on the Asian population revealed that out of 137 enrolled patients, 66 were from Asia, with 71% having EGFR mutations. Results indicated that the overall ORR for the Asian cohort was 42.4%, with a median DOR of 4.4 months, DCR of 80.3%, and mPFS of 5.4 months. Among EGFR-mutant patients, the ORR reached 48.9%, median DOR was 4.4 months, DCR was 87.2%, and mPFS was 5.7 months.

7.Dizal Pharmaceutical Releases International Phase 2 Data for Sunvozertinib

On May 28th, according to an abstract on the ASCO official website, data from Dizal Pharmaceutical's novel EGFR-TKI, Sunvozertinib, was selected for the Rapid Oral Abstract session at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The meeting is scheduled to take place in Chicago, USA, from May 31 to June 4. The study targets non-small cell lung cancer (NSCLC) patients with EGFR exon 20 insertion (exon20ins) mutations who have failed platinum-based chemotherapy. The data showed a best objective response rate (ORR) of 54.3% and a disease control rate (DCR) of 90.8%. According to Dizal Pharmaceutical's press release, this is the first time the company has publicly disclosed data from this study. EGFR exon20ins mutations are rare and challenging targets in NSCLC, accounting for approximately 2% to 4% of NSCLC cases. For over the past 20 years, patients with NSCLC harboring EGFR exon20ins mutations have lacked safe and effective targeted treatment options, creating an urgent need for new therapeutic choices.

Sunvozertinib is an oral, irreversible, highly selective EGFR-TKI targeting multiple EGFR mutation subtypes. It was approved by the China National Medical Products Administration (NMPA) in August 2023 for the treatment of locally advanced or metastatic NSCLC patients with confirmed EGFR exon20ins mutations who have progressed or are intolerant to prior platinum-based chemotherapy. The data presented at the ASCO meeting pertains to an international phase 2 registration study of Sunvozertinib for pre-treated NSCLC with EGFR exon20ins mutations. This is an open-label, international, multi-center phase 2 registration study currently being conducted in ten countries and regions worldwide, including the United States, Europe, and China. Patients were randomized based on baseline brain metastasis status and the number of prior systemic anti-cancer treatments. The primary endpoint of the study is the ORR as assessed by an independent review committee (IRC), with key secondary endpoints including duration of response (DoR) as evaluated by the IRC.

8.Bio-Thera Grants European Market Rights for Golimumab Biosimilar to STADA

On May 28th, Bio-Thera Solutions announced that it has entered into a licensing and commercialization agreement with STADA Arzneimittel AG for BAT2506. Under this agreement, STADA will have exclusive commercialization rights for BAT2506 in the European Union, the United Kingdom, Switzerland, and several other European countries. According to the terms of the agreement, Bio-Thera will be responsible for the development, production, and commercial supply of BAT2506, while STADA will handle its commercialization in the aforementioned regions. Bio-Thera is eligible to receive an upfront payment along with milestone payments, with the total amount reaching up to USD 157.5 million, in addition to a double-digit percentage of net sales as a royalty.

BAT2506 is a biosimilar of Golimumab developed by Bio-Thera in accordance with biosimilar guidelines issued by the Chinese NMPA, the US FDA, and the European EMA. Golimumab is an antibody targeting TNF-α, which can specifically bind with high affinity to both soluble and transmembrane human TNF-α, thereby blocking its interaction with TNF receptors (TNFR) and inhibiting TNF-α activity. BAT2506 has completed a global Phase III clinical trial.

9.Medilink Therapeutics and BioNTech Enter TMALIN® ADC Technology Platform Licensing Agreement

On May 27, Medilink Therapeutics announced a new strategic collaboration with BioNTech SE. Under this partnership, BioNTech has secured the exclusive option and corresponding global exclusive license to use Medilink's TMALIN® ADC technology platform to develop ADC products targeting certain specified innovative targets. According to the new agreement terms, Medilink Therapeutics will receive an upfront payment of $25 million (¥181 million) and is eligible to receive up to $1.8 billion in development, regulatory, and commercial milestone payments, as well as tiered royalties based on global annual net sales. As part of the agreement, Medilink Therapeutics will have the priority cooperation rights if BioNTech seeks to license or transfer these ADC products in any or multiple regions of Greater China (Mainland China, Hong Kong, Macau, Taiwan).

Back in October 2023, Medilink Therapeutics and BioNTech had already reached a strategic collaboration and global licensing agreement for an ADC project targeting HER3, and now the two parties have decided to further expand the scope of their cooperation. The signing of the platform cooperation licensing agreement marks a further consolidation of the strategic partnership between Medilink Therapeutics and BioNTech, laying a new foundation for their R&D collaboration in the ADC field.

Previously approved ADC drugs often suffered from limited therapeutic efficacy or developed resistance due to various constraints. However, the emergence of TMALIN® technology offers an effective solution to these challenges. Through a strong partnership with Harbour BioMed, the collaboration between Medilink's TMALIN® technology platform and Harbour's Harbour Mice® platform facilitated the IND approval of Harbour's first ADC drug HBM9033 in the United States. Additionally, Henlius Biotech successfully obtained exclusive, sublicensable rights from Medilink Therapeutics based on the TMALIN® platform targeting specific targets.