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Feliza Mirasol

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.

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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.

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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. 

Roche Introduces New Mass Spectrometry Analyzer

Roche announced results on Dec. 19, 2024 from a Phase IIb study (PADOVA) where prasinezumab, an investigational monoclonal antibody (mAb), failed to achieve statistical significance, missing the study’s primary endpoint. The study involved 586 patients with early stage Parkinson’s disease (PD) who were treated for a minimum of 18 months while on stable symptomatic treatment. Prasinezumab demonstrated potential clinical efficacy in the primary endpoint, which was time to confirmed motor progression, with a hazard ratio (HR)=0.84 [0.69-1.01] and p=0.0657, missing statistical significance, according to a company press release (1). The effect of prasinezumab, as evaluated in a pre-specified analysis, was more pronounced in the patients (75% of the participants) who were treated with levodopa, with results showing a HR=0.79 [0.63-0.99]. It was also observed that consistent positive trends occurred across multiple secondary endpoints as well as exploratory endpoints.

Prasinezumab also remains well tolerated and no new safety signals were observed in the study. Roche is evaluating the data further and will work together with health authorities to determine what steps to take next.

“Parkinson’s is complex and devastating with no disease modifying treatment options available for the millions of people impacted,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, Roche, in the press release (1). “We believe the consistent efficacy trends from the Phase IIb study of prasinezumab merit further exploration. We will continue our close collaboration with the Parkinson’s community as we further evaluate the data to determine next steps.”

Both a Phase II study (PASADENA) and this Phase IIb study (PADOVA) will continue to give Roche a chance to explore the observed effects in both studies. Full results from the Phase IIb (PADOVA) study are expected to be presented at an upcoming medical meeting.

Prasinezumab is part of a licensing, development, and commercialization agreement that Roche entered into with Prothena, an Ireland-based late-stage clinical biotechnology company with expertise in protein dysregulation. Under the agreement, formed in December 2013 (1), the companies aim to develop and commercialize mAbs that target α-synuclein, a presynaptic neuronal protein that is genetically and neuropathologically linked to PD (2). Prasinezumab targets the build-up of α-syn protein in the brain, which can potentially prevent further accumulation and spreading between cells. This action can slow down the progression of the disease (1).

“The results from the Phase [IIb] PADOVA study are a significant step forward to potentially bring the first disease-modifying treatment option to the millions of individuals living with Parkinson’s disease and their families,” said Gene Kinney, PhD, president and chief executive officer, Prothena, in that company’s press release (3). “As pioneers in developing the first anti-alpha synuclein targeting antibody, we look forward to Roche presenting the results from the PADOVA study at an upcoming medical conference and sharing with health authorities to determine the most appropriate path forward.”

1. Roche. Roche’s Phase IIb Study of Prasinezumab Missed Primary Endpoint, but Suggests Possible Benefit in Early-Stage Parkinson’s Disease. Press Release. Dec. 19, 2024.
2. Stefanis, L. α-Synuclein in Parkinson's Disease. 

 (2), a009399. DOI: 10.1101/cshperspect.a009399.
3. Prothena. Roche’s Phase IIb Study of Prasinezumab Missed Primary Endpoint, but Suggests Possible Clinical Benefit in Early-Stage Parkinson’s Disease. Press Release. Dec. 19, 2024.

Results from a Phase IIb study missed the primary endpoint by failing to achieve statistical significance. 

Prasinezumab Misses Primary Endpoint in Roche’s Phase IIb Study, but Has Potential in Treating Early Stage Parkinson’s Disease

Nicolas Pivet Cytiva discusses automation benefits process development analytics

Process Development Benefits from Automated Analytical Technologies

In an interview with the PharmTech Group, Nicolas Pivet, vice-president and general manager, Technology Solutions at Cytiva, notes that among the challenges in developing a biomanufacturing process is the process analytical technology (PAT) used in that process. Pivet discusses how automation benefits process development, especially when applied to analytics.

“I would say digital documentation is always helping with fast regulatory filing and tech transfer,” Pivet says, adding that, “What we've been experiencing in Cytiva is that many of our customers actually use a platform approach for process development, which is great for speed, but sometimes is not optimized for everything.”

“The introduction of recipe-driven equipment in process development has really enabled 24/7 utilization of labs, so, it's really enhancing the throughput of your lab staff,” Pivet says. The scientist, therefore, with the help of automation, can program lab equipment to rapidly execute experiments and collect samples. “What we've been seeing as well is that SCADA—the supervisory control and data acquisition system—is a layer that allows equipment information to be viewed together. That's why, in Cytiva over the past seven years, we've been developing our Figurate automation offering, which is a wide range of automation solutions and libraries, from historian to control systems with Unicorn [a control software] to SCADA with Wonderware [an automation platform] and to DCS [distributed control system] with Delta V and PlantPAx [types of DCS].”

In the area of PAT, Pivet feels that the bio/pharma industry needs to move faster. In the sensors space, for example, P80 sensors have been seeing an emergence of improved sensing technology. “Measuring CQAs [critical quality attributes], for instance, inline or online is really the holy grail of the biopharma industry right now,” Pivet says. “…The industry needs to get there in being able to measure CQAs inline and helping with real-time release, or right-time release, of the drug product.”

Nicolas Pivet, Vice-President and General Manager, Technology Solutions, Cytiva

Nicolas Pivet is vice-president and general manager, Technology Solutions, at Cytiva, where his ability to find the right creative solution—whether for customers, or when writing songs—is at the root of his delivery-focused mindset. Innovation is second nature to Pivet, which allows him to bring fresh approaches to meeting customer needs. He is a seasoned leader, with laser-sharp customer focus and experience across software and hardware R&D, program management, strategy, service operations, and commercial. Since 2023, Pivet has led Cytiva’s global Automation, Digital and Learning Solutions Business Unit, developing digital solutions enabling fast, flexible, and reliable process development and manufacturing for the biopharma industry. He also leads the Manufacturing Capacity Solutions unit, where Cytiva supports customers with powerful and innovative end-to-end solutions that transform biomanufacturing.

Cytiva's Nicolas Pivet, vice-president and general manager, Technology Solutions, emphasizes how automation benefits process development, particularly in the analytical space.

Orexo, a Sweden-based commercial-stage pharmaceutical company, announced on Dec. 17, 2024, that it has entered into a collaboration with Abera Bioscience (Abera), a Sweden-based platform and vaccine developer. Under the agreement, the companies will use AmorphOX, Orexo’s powder-based drug delivery technology, to develop mucosal vaccine candidates based on Abera's vaccine platform. This collaboration will be funded by Abera through grants it has previously received, mainly from the Coalition for Epidemic Preparedness Innovation (CEPI).

The AmorphOX technology is designed to improve properties of new or existing drugs. The technology aims to develop formulations that aid in significantly stabilizing active ingredients to enable alternative and more effective routes of administration. AmorphOX-based formulations are applicable for a range of active ingredients, from small molecules and peptides to larger biomolecules, such as vaccines, according to a company press release (1).

Orexo and Abera’s partnership will develop powder-based intranasal vaccine candidates with a focus on Abera's influenza vaccine candidate. Because an intranasal influenza vaccine has potential to easily and effectively reduce the spread of infections and prevent disease, they can play a significant role in controlling potential future pandemics.

“Influenza is a family of viruses that could mutate and cause the next pandemic, but seasonal influenza is already a major problem where vaccines are often not effective enough. Orexo has an impressive knowledge and technology for powder formulations of medicines that perfectly complements our expertise in vaccine development. Their innovative technology, AmorphOX, has shown to improve the properties of a wide range of different active ingredients. There is therefore great potential in this area, and we will be able to take many important development steps in the coming year,” said Maria Alriksson, CEO, Abera Bioscience, in the press release (1).

In a historical context, an influenza pandemic in 1918 caused at least 20 million deaths (2). Controlling another influenza pandemic will depend on innovations in vaccine production, according to researchers (3). A long-term goal for influenza vaccination should rely on a more universal vaccine, but there remains debate as to what exact traits a universal vaccine should have. A universal vaccine against all epidemic and pandemic viruses is not realistic, however, but having a vaccine that covers more drift variants may mean there could be less need for vaccine updates and a reduced need for yearly vaccinations, researchers note (4).

“Abera has an innovative and promising vaccine platform for the development of mucosal vaccines, as confirmed by their recent funding from CEPI. The collaboration is fully in line with our strategic development of the AmorphOX platform, and, through collaborations, we can showcase the potential and value of our technology. We look forward to working with Abera, where our experience and technologies are highly complementary,” said Robert Rönn, senior vice-president and head of R&D at Orexo, in the press release (1).

1. Orexo. Orexo Enters into Collaboration with Abera to Develop Nasal Powder Vaccines Based on the Amorphox Technology. Press Release. Dec. 17, 2024.
2. Crosby, A.W. 

America’s Forgotten Pandemic: The Influenza of 1918

; Cambridge University Press, 1989.
3. Kilbourne, E. D. Influenza Pandemics: Can We Prepare for the Unpredictable? 

 (3). DOI: 10.1089/vim.2004.17.350
4. Kim, H.; Webster, R. G.; Webby, R. J. Influenza Virus: Dealing with a Drifting and Shifting Pathogen. 

The companies will use Orexo’s powder-based drug delivery technology to develop mucosal vaccines in an inhaled formulation.