Feliza Mirasol is the science editor for 

Feliza Mirasol

The Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Takeda's HYQVIA [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] to treat patients with agammaglobulinemia or hypogammaglobulinemia, Takeda announced on Dec. 27, 2024. Agammaglobulinemia and hypogammaglobulinemia are disorders characterized by very low or absent levels of antibodies. Patients suffering from these disorders have an increased risk of serious recurring infection caused by primary immunodeficiency (PID) or secondary immunodeficiency (SID) (1,2). This approval makes HYQVIA the first and only facilitated subcutaneous immunoglobulin (fSCIG) therapy to be made available as a treatment option for patients in Japan, according to a company press release. HYQVIA is also under review in Japan for additional indications.

The approval is based on data from two pivotal Phase III trials that evaluated the efficacy, safety, tolerability, and pharmacokinetics in Japanese patients with PID. Data from two Phase III clinical trials in patients with PID in North America were also included in the MHLW submission.

“We are delighted that HYQVIA, approved in more than 40 countries worldwide, has now been approved in Japan,” said Naoyoshi Hirota, regional head of Research & Development for Takeda’s Plasma-Derived Therapies Business Unit in Japan, in the press release (1). “The subcutaneous IG therapies currently available in Japan for patients with agammaglobulinemia or hypogammaglobulinemia require infusion once every week or every two weeks. We are proud to offer Japanese patients the first and only facilitated subcutaneous treatment option that offers a reduced dosing frequency of every three or four weeks.”

HYQVIA comprises a combination of one vial of IG 10% and one vial of recombinant human hyaluronidase PH20 (rHuPH20); rHuPH20 increases the dispersion and absorption of IG in the subcutaneous tissue. This increased dispersion and absorption allows for larger volumes to be infused at the infusion site, which in turn allows for less frequent dosing compared to other subcutaneous IG products. Meanwhile, this route of administration can avoid the need to access veins for delivering the therapy. Takeda noted in its press release that the ability to infuse a larger infusion volume is expected to increase administration flexibility for patients with agammaglobulinemia or hypogammaglobulinemia by decreasing the dosing frequency to once every three or four weeks, compared to the weekly or bi-weekly dosing schedule with conventional SCIG treatments.

“There is a high unmet need for plasma-derived therapies (PDTs) in patients in Japan, which is anticipated to increase as education and timely diagnosis rates continue to improve,” said Kristina Allikmets, head of R&D for Takeda’s Plasma-Derived Therapies Business Unit, in the release. “The approval of HYQVIA, the first and only facilitated SCIG treatment, is further evidence of Takeda’s commitment to add to the standard of care for patients in Japan. We look forward to continuing to bring new therapeutic options that support and enhance the experience of patients in our home country throughout the next decade.”

The approval follows Takeda’s previous announcement in March 2023 that the company is investing ¥‎100 billion (US$754 million at the time of the announcement; current conversion is US$635 million) into 

building a new manufacturing facility for plasma-derived therapies (PDTs) in Osaka, Japan

1. Takeda. Takeda Announces Approval of HYQVIA 10% S.C. (Subcutaneous) Injection Set in Japan for Patients with Agammaglobulinemia or Hypogammaglobulinemia. Press Release. Dec. 27, 2024.
2. Pimenta, F. M. C. A.; Palma, S. M. U.; Constantino-Silva, R.N.; Grumach, A.S. Hypogammaglobulinemia: A Diagnosis that Must Not Be Overlooked. 

 (10), e8926. DOI: 10.1590/1414-431X20198926
3. Takeda. Takeda to Invest 100 Billion JPY in a New Manufacturing Facility for Plasma-Derived Therapies in Japan. Press Release. March 23, 2023.

Articles

With this approval, HYQVIA [Immune Globulin Infusion 10% (human) with Recombinant Human Hyaluronidase] becomes the first and only facilitated subcutaneous immunoglobulin available in Japan to treat these disorders.

Takeda Receives Japanese Regulatory Approval for HYQVIA Subcutaneous Injection for Treating Agammaglobulinemia or Hypogammaglobulinemia

Innovent Biologics (Innovent), a China-based biopharmaceutical company specializing in treatments for oncology, cardiovascular and metabolic, autoimmune, ophthalmology, and other major diseases, announced on Jan. 2, 2025 that it has entered into a collaboration and exclusive license agreement with Roche. The companies will advance the development of IBI3009, Innovent’s novel delta-like ligand 3 (DLL3)-targeted antibody drug conjugate (ADC) candidate. The collaboration is aimed at bringing innovative treatment options to patients with advanced small cell lung cancer (SCLC).

Under the agreement, Roche receives exclusive global rights to develop, manufacture, and commercialize IBI3009; however, the two companies will jointly focus on the early stage development of the candidate. After early stage development, Roche will take over full development. Innovent, in turn, will receive an upfront payment of $80 million and is eligible to receive up to $1 billion in development and commercial milestone payments. Innovent is also eligible to receive tiered royalties on net sales.

“We are delighted to once again enter a strategic collaboration with Roche, a global leader in oncology, to advance our potentially best-in-class DLL3 ADC candidate. By combining Roche's scientific expertise and global development capabilities with our innovative approach, we are taking a significant step forward in our mission—to empower patients worldwide with affordable, high-quality biopharmaceuticals,” said Samuel Zhang, PhD, chief business officer, Innovent, in the press release (1).

DLL3 is an antigen with low expression in normal tissues but is significantly overexpressed in certain cancers, particularly SCLC and other neuroendocrine tumors, making it an attractive target for emerging therapy development (2). IBI3009 has already received investigational new drug (IND) approvals in the United States, China, and Australia and is currently in a Phase I study.

IBI3009 was developed using Innovent’s proprietary novel topoisomerase 1 inhibitor (TOPO1i) platform. It has shown positive anti-tumor activity in multiple tumor-bearing mouse models, particularly chemo-resistant tumor types. The ADC has also demonstrated a favorable safety profile, according to the company press release.

“We are excited to enter this partnership with the Innovent team to further develop this promising investigational treatment for patients with small cell lung cancer. This partnership builds on Roche’s long history of innovation in the area of ADCs, to address the unmet needs of patients with solid tumors with transformational medicines,” said Boris L. Zaïtra, head of Corporate Business Development, Roche, in the release.

Innovent has four new drug applications under regulatory review, and the company’s pipeline includes three assets in Phase III or pivotal clinical trials with 17 more molecules in early clinical stage. Innovent’s global partners include Eli Lilly and Company, Sanofi, Incyte, Adimab, LG Chem, and MD Anderson Cancer Center.

1. Innovent Biologics. Innovent Enters into Exclusive Global License Agreement with Roche for Novel DLL3 Antibody Drug Conjugate. Press Release. Jan. 2, 2025.
2. Rudin, C. M.; Reck, M.; Johnson, M. L.; et al. Emerging Therapies Targeting the Delta-like Ligand 3 (DLL3) in Small Cell Lung Cancer. 

Under the agreement, the companies will advance development of IBI3009, Innovent’s ADC candidate, which has received IND approvals in the US, China, and Australia.

Roche Forms Partnership Worth Potentially More than $1 Billion with Innovent to Develop Novel ADC for SCLC

on Dec. 31, 2024, FDA announced the reopening of the comment period for the 

 notice (FRN), “Evaluating the Immunogenicity Risk of Host Cell Proteins in Follow-on Recombinant Peptide Products: Establishment of a Public Docket: Request for Information and Comments”, published on July 25, 2024 (89 

 60436) (2). The comment period has been reopened due to high interest from the industry for the FRN. The comment period will remain open until March 3, 2025 (1).

The December 31 notice establishes a public docket under which substantive comments from interested parties can be submitted on evaluating the immunogenicity risk of host cell proteins (HCPs) in follow-on peptide products. FDA is specifically interested in comments that address suitable methods to detect, identify, and control HCPs in commercial lots of recombinant peptide products (including information on achievable residual amounts of HCPs in the drug product) as well as 

 immunogenicity assessment (IVISIA) of host cell proteins in recombinant peptide products.

Comments can be submitted electronically or in writing. If sent electronically, comments, including any attachments, should be submitted to the Federal eRulemaking Portal at 

. Comments and any accompanying attachments will be posted to the docket unchanged, according to FDA. “Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov,” FDA states in the December 31 notice (1).

Comments that contain confidential information not for public consumption should be submitted as a written/paper submission only.

For written/paper submissions, comments should be submitted by mail, hand delivered, or sent by courier to: Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. For comments submitted in writing, FDA will post the comments, as well as any attachments—except for information submitted that is marked and identified as confidential.

FDA also instructs that all submissions received must include the Docket No. FDA-2024-N-2980 for “Evaluating the Immunogenicity Risk of Host Cell Proteins in Follow-On Recombinant Peptide Products; Request for Information and Comments.”

Written/paper submissions that are confidential should be submitted in two copies, with one copy including the information marked as confidential. FDA recommends using a heading or cover note that states “THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.” The agency will review this copy, including the claimed confidential information, in its consideration of comments, while the second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov.

“Although follow-on recombinant peptide products can rely on FDA’s findings of safety and effectiveness for a listed drug that is a peptide product, differences in recombinant expression systems used during the peptide production could result in quality attribute differences, including in the host cell protein profile, which in turn, could contribute to differences in immunogenicity risk between a follow-on peptide product and the relied upon listed drug,” FDA states in its announcement. Public comments will help the agency develop recommendations for evaluating and mitigating the immunogenicity risk associated with differences in HCP profiles between the follow-on and listed drug.

For more information about the open docket, including what information to include when submitting comments, see the 

Evaluating the Immunogenicity Risk of Host Cell Proteins in Follow-On Recombinant Peptide Products; Reopening of the Comment Period

Evaluating the Immunogenicity Risk of Host Cell Proteins in Follow-On Recombinant Peptide Products; Establishment of a Public Docket; Request for Information and Comments

The comment period for the Federal Register Notice, “Evaluating the Immunogenicity Risk of Host Cell Proteins in Follow-on Recombinant Peptide Products: Establishment of a Public Docket: Request for Information and Comments”, has been reopened by FDA until March 3, 2025.

FDA Announces Reopening of Comment Period Regarding HCP Immunogenicity Risk from Follow-on Recombinant Peptides

Atul Mohindra Lonza challenges successes bispecific antibodies future direction CDMO perspective

Bispecific Antibody Development and Where It’s Headed

The biopharmaceutical industry's increasing shift toward precision medicines has led to a growing need for enhanced potency and the establishment of novel mechanisms of action, says Atul Mohindra, head of Biologics R&D at Lonza. From Lonza’s perspective, therefore, there is a shift in which the development of monoclonal antibodies is moving toward more complicated formats of molecules.

“When it comes to analytical methods, some of the molecule types that we see in the industry [are] becoming extremely complicated,” Mohindra says. “Within the FDA-approved products, there's a minimal amount right now that … are bispecifics. However, when you look at the pipeline of products that are coming through in Phase I, Phase II, there's an enormous wave of these complex proteins that are coming through.”

“The need for increasing precision medicine [and] reducing off target events is always going to be there, and I think that's exactly where the industry needs to head,” Mohindra adds. “Along with that will come the increased use of AI technologies and, also, the increased use of analytical testing technologies. When you combine all of that with more efficient bioprocessing, such as continuous bio processing, I think that's where the future is going to be.”

Mohindra sees advancement in the use of more complex proteins with more wider applications, such as autoimmune diseases, neurological disorders, and infectious diseases. “But,” he qualifies, “that ultimately will require and push the industry to advance when it comes to analytical technologies [and also] drive the industry towards using more cost effective bioprocess solutions.”

Atul Mohindra, Head of Biologics R&D, Lonza

Atul Mohindra serves as the head of R&D Biologics at Lonza and has been with the company for almost 20 years. He is responsible for leading a global team of over 200 scientists that develop and implement innovative technologies at Lonza’s Biologics. Throughout his career, he has successfully developed and implemented several novel cell culture, purification, and analytical platform processes for multiple innovator and biosimilar programs. Mohindra also serves as a board observer for Affinia Therapeutics, a biotech company focused on gene therapies.

Videos

In a discussion on bispecific antibody development, Atul Mohindra, head of Biologics R&D at Lonza, points out the challenges and successes of these molecules as well as the field’s future direction from a CDMO perspective.

FDA announced on Dec. 23, 2024 that it has approved Hikma Pharmaceuticals USA’s liraglutide injection, the first generic referencing Victoza (liraglutide injection) 18 mg/3 mL from Novo Nordisk. Liraglutide injection is a glucagon-like peptide-1 (GLP-1) receptor agonist. Hikma Pharmaceuticals’ generic version is indicated for improving glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes as an adjunct to diet and exercise.

There is currently a drug shortage of liraglutide injection and certain other GLP-1 medications, according to FDA in a press release (1). The agency is thus prioritizing assessment of generic-drug applications for drugs in shortage to help improve patient access to these medications.

“[FDA] supports development of complex generic drugs, such as GLP-1s, by funding research and informing industry through guidance as part of our ongoing efforts to increase access to needed medications,” said Iilun Murphy, MD, director of the Office of Generic Drugs in FDA’s Center for Drug Evaluation and Research, in the press release (1). "Generic drugs provide additional treatment options which are generally more affordable for patients. Today’s approval underscores [FDA’s] continued commitment to advancing patient access to safe, effective, and high-quality generic drug products.”

Liraglutide improves blood sugar levels by having similar effects in the body as GLP-1 in the pancreas. There are often insufficient levels of GLP-1 in type 2 diabetes patients. More than 38 million people in the United States have diabetes, and 90% to 95% of those individuals have type 2 diabetes, according to the Centers for Disease Control and Prevention (1).

FDA, meanwhile, has been addressing challenges related to the development of generics and the promotion of more generic competition. Addressing these challenges is a key part of the agency’s Drug Competition Action Plan and its efforts to help increase patient access to medicines.

The development of complex drug products such as liraglutide can be even more difficult because of their complex active ingredient, formulation, or mode of delivery. For these reasons, many complex drugs lack generic competition. Thus, to address this issue and enable timely development and approval of needed medications, especially complex products, FDA has been working to clarify regulatory expectations for applicants early in the development process, which includes the agency’s guidances for industry and the pre-abbreviated new drug application program. “These efforts make it more feasible for manufacturers to develop generic drugs and can enhance patient access to treatment by helping make these products more available, allowing patients in the United States to obtain the medicines they need,” FDA stated in its press release (1).

FDA had earlier approved the first generic in this class of medications in November 2024, when it approved a generic referencing Byetta (exenatide). The approval for the generic exenatide 1.2 mL and 2.4 mL prefilled pen injection was granted to Amneal Pharmaceuticals (2).

1. FDA. FDA Approves First Generic of Once-Daily GLP-1 Injection to Lower Blood Sugar in Patients with Type 2 Diabetes. Press Release. Dec. 23, 2024.
2. Amneal Pharmaceuticals. Amneal Resubmits DHE Autoinjector New Drug Application and Receives U.S. FDA Approval of Exenatide, its First Generic Injectable GLP-1 Agonist. Press Release. Nov. 21, 2024.

FDA's approval of Hikma Pharmaceuticals’ liraglutide injection makes this product the first generic version of Victoza, a GLP-1 receptor agonist.

First Generic of a GLP-1 Injection Gets FDA Nod to Treat Type 2 Diabetes

Roche has launched its cobas Mass Spec solution upon receiving the Conformite Europeenne (CE) mark approval for the product, including its cobas i 601 analyzer and what the company noted in a Dec. 18, 2024  press release is the first Ionify reagent pack of four assays for steroid hormones (1). The CE mark represents the first milestone in the global launch of the cobas Mass Spec solution. The offering aims to bring automated, integrated, and standardized clinical mass spectrometry testing to routine laboratories globally.

Following the launch, Roche will roll out a cobas Mass Spec solution menu offering that comprises more than 60 analytes for testing steroid hormones, vitamin D metabolites, immunosuppressant drugs (ISD), therapeutic drug monitoring (TDM), and drugs of abuse testing (DAT). The new offering will handle sample preparation through to result interpretation, and with it, Roche will be consolidating four technologies—ion selective electrode (ISE), clinical chemistry, immunochemistry, and mass spectrometry—onto a single platform, which the company expects will maximize efficiency and deliver enhanced medical value. The solution is designed to enable smart testing by leveraging physical and digital connectivity with other analytical units (2).

“The cobas Mass Spec solution will fundamentally change the field of clinical diagnostics,” said Matt Sause, CEO of Roche Diagnostics, in the press release (1). “The solution would make fully standardized clinical mass spectrometry more broadly available with the potential to improve patient care worldwide. For example, in breast cancer patients receiving hormone therapy, mass spectrometry can help physicians detect subtle changes in therapeutic response earlier, allowing for timely adjustments to treatment.”

Because mass spectrometry offers high specificity, sensitivity, and accurate analysis, it is considered the diagnostic “gold standard” for various clinical applications, such as measurements of steroid hormones in endocrinology, vitamin D testing, and the monitoring of immunosuppressants and therapeutic drugs, according to Roche in the press release. Mass spectrometry can benefit healthcare systems by, for example, monitoring the effective and responsible use of antibiotics as well as ongoing monitoring of disease progression and treatment. In addition, the high specificity of testing can provide greater levels of clarity to physicians, which would enable them to make more timely treatment decisions for patients.

In the meantime, Roche’s development of new, proprietary chemistry technology makes commercial automation possible and enables a workflow that is much more environmentally sustainable than current methods. “Until now, mass spectrometry has only been offered by specialist laboratories due to the low level of automation, integration and standardization, and the high complexity of the workflows that require highly skilled operators. This has resulted in great variability between different laboratories and long processing times,” the company stated in its release (1).

The cobas Mass Spec solution will be included in Roche’s established cobas pro integrated solutions product line, which enables full integration into clinical chemistry and immunochemistry testing as well as lab automation and IT.

1. Roche. Roche Transforms Mass Spectrometry Diagnostics with Launch of Cobas Mass Spec Solution. Press Release. Dec. 18, 2024.
2. Roche. cobas i 601 Analyzer. 

The launch of Roche's cobas mass spectrometry solution will bring fully automated mass spec analysis to the clinical lab. 