Feliza Mirasol is the science editor for 

Feliza Mirasol

Chime Biologics, a China-based contract development and manufacturing organization, announced on June 30, 2023 that it has established three-way strategic collaboration with Nanjing Leads Biolabs (Leads Biolabs), a China-based clinical-stage R&D biotech company, and BeiGene, a biotechnology company with headquarters in China and the United States. The goal of this collaboration is to accelerate the development and global manufacturing of LBL-007, a novel monoclonal antibody (mAb) that was developed independently by Leads Biolabs for cancer treatment.

Phase I clinical trial data of LBL-007 in patients with later-stage solid tumors were announced at the 2021 annual meeting of the American Society of Clinical Oncology, according to a company press release. LBL-007 is currently moving into the clinical Phase II stage.

Leads Biolabs had previously reached an authorization and cooperation agreement with BeiGene under which Leads Biolabs granted an exclusive global development and production license to BeiGene for the mAb, as well as a commercial manufacturing license outside China.

Under the new three-way collaboration, Chime Biologics will cooperate with Leads Biolabs to accelerate the filing of an investigational new drug (IND) application and provide clinical trial materials in China. To achieve IND filing, Leads Biolabs has provided Chime Biologics with its supporting data and information related to the production of LBL-007 and clinical trial materials in mainland China.

Meanwhile, BeiGene and Chime Biologics are also establishing a strategy to facilitate IND applications overseas and clinical trial materials supply outside of China. BeiGene is also providing Chime Biologics support for clinical development and manufacturing of clinical trial materials to enable multiple clinical trials. The companies are seeking indications in colorectal cancer, non-small cell lung cancer, head and neck squamous cell carcinoma, and other solid tumors. According to the press release, clinical trials have been conducted in various countries worldwide, including Australia and the United States.

“We are so pleased to cooperate with BeiGene … and Chime Biologics … LBL-007 is the first innovative antibody drug with global intellectual property which we developed independently. I believe that the development and commercialization of LBL-007 can be expedited through our triangular cooperation, so we can address unmet medical needs and bring hope to cancer patients,” said Kang Xiaoqiang, founder, chairman, and CEO of Leads Biolabs, in the release.

“[LBL-007] has launched nearly ten Phase I and II clinical trials worldwide in the last year, with indications covering colorectal cancer, non-small cell lung cancer, head and neck squamous cell cancer, melanoma, and other solid tumor cancers. I believe that this cooperation will bring new opportunities for the medical community to further conquer cancer,” said Wang Lai, global R&D director of BeiGene, in the release.

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Chime Biologics, Leads Biolabs, and BeiGene have formed a three-way collaboration to advance the development and global manufacturing of Leads Biolabs’ lead mAb candidate, LBL-007.

Chime Biologics Forms mAb Development and Manufacturing Deal with Leads Biolabs and BeiGene

On June 29, 2023, FDA announced that it approved Roctavian (valoctocogene roxaparvovec-rvox), an adeno-associated virus vector-based gene therapy from BioMarin Pharmaceutical for treating severe hemophilia A. The therapy is indicated for adults without pre-existing antibodies to adeno-associated virus serotype 5 detected by an FDA-approved test.

According to an agency press release, FDA’s decision marks the first approval for a gene therapy to treat adults with severe hemophilia A. Hemophilia A is a rare genetic bleeding disorder that primarily affects males and occurs when there is a mutation in the gene that produces factor VIII (FVIII), a blood-clotting protein. Severe hemophilia A manifests when there are especially low levels of FVIII (less than 1% in the blood); according to the release, this disorder represents approximately 60% of all cases.

Valoctocogene roxaparvovec-rvox is a one-time, single-dose gene therapy (viral vector carrying a gene for FVIII) that is given intravenously. It is designed to replace the function of the mutated gene, thus allowing severe hemophilia A patients to produce their own FVIII and limit bleeding episodes, according to a BioMarin company press release.

“Hereditary hemophilia A is a potentially serious bleeding disorder. Severe cases of hemophilia A can cause life-threatening health issues due to increased risk of uncontrolled bleeding,” said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, in the agency’s press release. “Today’s approval represents an important advance in providing treatment options for patients with this bleeding disorder, and treatment with gene therapy may reduce the need for ongoing routine therapy.”

According to BioMarin’s press release, valoctocogene roxaparvovec-rvox will be manufactured at the company's facility in Novato, Calif., from where BioMarin expects to meet commercial demand throughout the product’s lifecycle.

FDA has approved Roctavian (valoctocogene roxaparvovec-rvox), a gene therapy from BioMarin Pharmaceutical for treating severe hemophilia A in adults.

FDA Approves BioMarin’s Roctavian, the First Gene Therapy for Treating Severe Hemophilia A

A crucial step in achieving approval of a biosimilar is establishing analytical and clinical biosimilarity with the innovator biologic (i.e., reference product). Analytical biosimilarity studies therefore aim to demonstrate a highly similar profile taking into account variations in critical quality attributes (CQAs) of the biosimilar product. Such variations, however, must fall within a range set by the innovator.

Biosimilarity studies should consist of detailed comparative structural and functional characterizations, the data for which must be gathered using appropriate, validated analytical methods. These analytical methods must not only fingerprint the molecule in question but must also help reduce the cost (economic burden) that would otherwise be incurred in meeting regulatory requirements for extensive preclinical/clinical similarity data (1). In reducing cost at the biosimilarity study stage, it makes sense that the biosimilar product can thus be more affordable than its innovator.

Luckily for the biopharma industry, biosimilar manufacturing processes and the regulations associated with getting approval for them have become more well established in the past decade, as evidenced by the number of biosimilar drug approvals during that timeframe. It has also been helpful that biosimilarity studies that have been conducted (with an eye toward gaining regulatory approval) are being published more frequently and being made public, making access easier. As a result, some technical advancements that have been made in analytical sciences have found their way into techniques used for biosimilar assessment (1).

® delved into the challenges and advancements made in analytical methods for biosimilar characterization with Stephen Pagnotta, executive director and biosimilar commercial lead at Boehringer Ingelheim.

 What is meant by ‘implementation of orthogonal tools’, and why are orthogonal tools important for biosimilar studies?

 Orthogonal tools or techniques are laboratory methods used to characterize the structure of a molecule or protein. To build a complete physiochemical profile of a biotherapeutic, multiple orthogonal assessments are used to capture different aspects of a molecular structure. These techniques include, but are not limited to, peptide mapping, mass spectrometry, circular dichroism, and analytical ultracentrifugation.

Orthogonal tools are important for biosimilar studies because researchers must establish that the biosimilar is structurally like the reference product so that there is no clinically meaningful difference in terms of safety, efficacy, purity, and potency.

 What analytical advancements have been made that have boosted the ability to conduct biosimilar studies?

 Biosimilar development requires extensive analytical comparison of medicine structure and function to ensure biosimilarity to the reference product. Analytical method development is a procedure for reliable detection of analytes of interest. High-grade method development ensures that the method is suitable for full validation and high-quality analysis of medicines, metabolites, and biomarkers in biological matrices. Advances in analytical techniques have resulted in more rapid results, increased reproduction validation, and higher selectivity and specificity.

During research, the developed analytical methods are utilized to measure and define the required dosage, acceptable impurity, observed stability, and bioavailability of the medicine overall.

 Why is it so challenging to demonstrate biosimilarity with respect to CQA variations between the biosimilar product and its innovator?

 Biotherapeutics are more structurally complex compared to small-molecule medicines, and this complexity requires manufactures to use advanced analytic methods to verify structural similarity between the biosimilar and its reference product.

 Industry dialogue revolves around the two concepts: biosimilarity and interchangeability. What are the differences between the two terms and what is the impact on a biosimilar product’s trajectory on the regulatory pathway to approval?

 A biosimilar is a version of a biologic medication that is made by a different company than the one that invented it, with no clinically meaningful differences in terms of safety, potency, and purity.

An interchangeable biosimilar first must meet the high FDA standards of a biosimilar. Then, to achieve the interchangeable designation, the biosimilar must be supported by additional FDA-required data, generally through one or more studies of multiple substitutions in patients, known as an interchangeability study.

An interchangeability study shows how patients do when they are switched back and forth from a reference product to the interchangeable biosimilar. The interchangeability study is designed to demonstrate that patients can be switched with no increased risk in terms of safety or diminished efficacy, as compared to remaining on the reference product. The FDA interchangeability designation enables auto-substitution at the pharmacy level. Individual state laws control how and whether providers must be notified.

 Why is it important to develop new analytical methodologies not traditionally used in biosimilar studies?

 Biosimilar development follows the regulatory authority guidelines such as those from the FDA and EMA [European Medicines Agency]. As the number of medicines released in the market is increasing by the day, so is the need for method development and validation. These new medicines may be compounds never used before or modifications of existing medicines. An inability to relay analytical procedures, as well as reference and internal standards for new medicines, could hinder thorough R&D. Hence, it becomes necessary to develop new analytical methods for studying the effect of medicinal compounds. These methods are designed to understand the identity, characteristics, purity, and potency of medicinal compounds.

1. Nupur, N.; Joshi, S.; Gulliarme, D.; Rathore, A. S. Analytical Similarity Assessment of Biosimilars: Global Regulatory Landscape, Recent Studies and Major Advancements in Orthogonal Platforms. 

When evaluating a drug’s risk assessment for elemental impurities, one must consider all aspects of its lifecycle.

Using Analytical Advancements to Assess Biosimilarity

On June 22, 2023, Andelyn Biosciences, a cell and gene therapy (CGT) contract development and manufacturing organization, announced the opening of its newly constructed manufacturing headquarters in Columbus, Ohio. According to a company press release, the 180,000-ft2 facility is intended to complement Andelyn’s two existing facilities in Columbus.

The new facility houses laboratory and manufacturing space, is regulatory-compliant, and more than triples Andelyn’s footprint to meet the growing demand for CGT services.

“The new facility includes 16 [C]GMP [current good manufacturing practice] modular manufacturing suites with upstream, downstream, solution prep, and filling capabilities, along with quality control labs and warehouse and corporate headquarters space,” said Wade Macedone, CEO, Andelyn Biosciences, in a company press release. “We are proud of our record of success in this demanding field, with over 2000 viral vector production runs and more than 450 [C]GMP batches delivered in support of more than 75 global gene therapy clinical trials.”

The new headquarters located in Columbus, Ohio, more than triples Andelyn Biosciences’ footprint to meet growing demand for CGT services.

Andelyn Biosciences Opens New CGT Manufacturing Headquarters

The Public Investment Fund (PIF), Saudi Arabia’s global investment organization, announced on June 18, 2023 that it has launched Lifera, a commercial-scale contract development and manufacturing organization (CDMO). The CDMO will enable growth of the local bio/pharmaceutical industry, strengthen national resilience, and support Saudi Arabia’s position as a global pharmaceutical manufacturing destination.

Lifera will focus on the manufacture of essential biopharmaceutical products, including insulins, vaccines, plasma therapeutics, monoclonal antibodies, cell and gene therapies, and innovative small molecules. The company will also create partnerships with leading local and international companies as well as attract targeted investments in a bid to grow local capacity and strengthen domestic manufacturing in this sector.

A part of Lifera’s goals is to drive formulation development, medicine development, and manufacturing. The company also intends to increase testing services for sterile bio/pharmaceutical products.

“PIF is investing to enable a leading health sector in Saudi Arabia, supporting the development of and access to advanced medicines and treatments. Biologics represents one of the most critical and fastest-growing pharmaceutical segments, both in Saudi Arabia and globally,” said Yazeed A. Al-Humied, deputy governor and head of Middle East and North Africa (MENA) Investments at PIF, in a company press release. “Lifera intends to partner with leading companies in the sector to localize manufacturing, attract investment, and enable the private sector to scale up, ensuring easier access for patients, whilst securing supply of life-saving medicines that can meet local, regional, and global demand.”

PIF has established Lifera, a new manufacturing entity that will manufacture, stockpile, and supply bio/pharmaceuticals both locally and through partnerships.

Saudi Arabia’ PIF Launches Lifera, a New CDMO

Choose New Jersey, a nonprofit economic development organization for the state of New Jersey, announced on June 15, 2023 that Enzene Biosciences, a Pune, India-based biotech company will invest $50 million to open a new biopharmaceutical manufacturing plant on the Princeton West Innovation Campus in Hopewell, NJ. The facility is expected to start up in June 2024 and is the company’s first location outside of India, according to a press release issued by the nonprofit.

Enzene is a contract development and manufacturing organization and a subsidiary of Alkem Laboratories, an Indian pharmaceutical company. As part its expansion plans, Enzene will initially hire 50 employees and grow to 300 employees at the New Jersey facility.

The placement of the facility is intended to provide North American biopharmaceutical companies with streamlined supply chains, quick turnaround times, enhanced communication, and greater control over the manufacturing process, according to the press release. Enzene expects to support the development and production of a diverse range of biologics at the facility.

“The strong relationship between New Jersey and India has gained increasing momentum since we opened the New Jersey India Center to cultivate economic opportunities during our trip to the country in 2019,” said NJ Governor Phil Murphy, in the press release. “I am proud to welcome Enzene Biosciences and their expanding global presence to New Jersey’s flourishing life sciences industry. New Jersey’s favorable business environment, skilled workforce, strategic location, supportive ecosystem for growth, and deep cultural ties are why Indian companies thrive in our state.”

“Enzene Biosciences is thrilled to establish our manufacturing operations in New Jersey, as it allows us to extend our local manufacturing capabilities to our valued North American clients,” said Himanshu Gadgil, CEO of Enzene Biosciences, in the release. “We are excited to provide them with access to our cutting-edge continuous manufacturing platform, which enables streamlined and efficient production processes. New Jersey’s highly skilled workforce, state-of-the-art infrastructure, and renowned academic institutions make it an ideal location for Enzene, ensuring that we can deliver exceptional services and support to our clients in the [United States].”

India’s Enzene Biosciences is investing $50 Million into a new biopharma manufacturing plant in Hopewell, NJ.