Aligning mRNA Progress with Regulatory Streamlining

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Drug Solutions Podcast: 

Employing novel technologies and more patient-centric approaches

Integrating Strategies for Formulation Success

Delving into Biopharmaceutical Development and Manufacturing

Drug Digest: 

 Quality Considerations in Changing Excipient Providers

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Chris Spivey is director of Industry Relations and Strategic Partnership, MJH Life Sciences.

Marianna Tcherpakov, PhD, director of Business Development, CMC Services, at Frontage Laboratories, spoke on the CDMO’s role in tackling complex technical challenges to enable startup biotechs solve scale up problems.

BIO 2024: CDMOs Focus on Complex Technical Challenges to Boost Startup Biotechs

Contract development and manufacturing organization (CDMO) Frontage Laboratories founder Song Li, PhD, who currently holds the position of executive chairman, board of directors, at the company, first set up a testing laboratory in Thorofare, NJ, with a focus on analytical and bioanalytical testing that quickly established a reputation for expertise. That foundation of expertise seems to have stayed fairly well intact, and science—and scientists—driving projects forward appear to be the key selling point for this CDMO, which says of itself, “our scientific knowledge base, technical expertise and reputation for high quality services have been integral to our ability in turning our services into your solutions” (1). In speaking with the company’s staff at BIO 2024, Pharmaceutical Technology Group’s Chris Spivey discerned that the practical upshot for the company has been that Frontage Laboratories often attracts the more vexing or technically challenging projects, and as a result, the company’s teams are now well situated to deal with the more difficult of perplexing projects for which others may not be as well prepared. As an example of the company’s preparedness, it states on the resources section of its website that it uses a next-generation sequencing (NGS)-based method, called the Frontage PGx NGS Test, to rapidly determine the genotype of 300+ genes involved in absorption, distribution, metabolism, and excretion (2).

Talking with Spivey at BIO, Marianna Tcherpakov, PhD, director of Business Development, CMC Services, Frontage Laboratories, at BIO, outlined the general approach the company takes when working with clients. She emphasized that the company’s approach is always customizable and personalized to not only the science the client requires but also to their specific strengths and weaknesses as an organization. “We look at your project as our own product. We therefore offer fast delivery, fast responses to client questions, almost as if we are holding hands … Many come from smaller startups that need a lot of guidance. [This] can be technical, it might be regulatory, but it all relies on our very strong scientific base,” Tcherpakov said. “We are passionate about technology,” she added.

Many of the PhD staff at Frontage Laboratories have come from other companies in the industry, and Tcherpakov pointed out that these past experiences and learnings are often brough to bear on the current project challenge. “We understand how stressful it can be for the smaller biotech, and even middle-sized [biotechs], when you have a lot of deadlines. You have clinical trials submissions coming up, and you need to be on top of everything, and fast,” she said.

Touting their scientific backbone Frontage Laboratories advertises itself as “more than a CRO”, in that it is also a “full global pharmaceutical development organization. Frontage Laboratories offers a comprehensive suite of drug discovery and development services including chemistry, DMPK [drug metabolism and pharmacokinetics], preclinical safety/toxicology, and clinical trial services with strategic and regulatory support to effectively bring new lead candidates through the IND [investigational new drug] stage to Phase II” (3).

BIO 2024 was held on June 3–6 in San Diego, Calif.

1. Frontage Laboratories. Services & Solutions. 

 (accessed August 21, 2024).
2. Frontage Laboratories. Resource Library. 

 (accessed August 21, 2024).
3. Frontage Laboratories. About Frontage. 

Marianna Tcherpakov, PhD, is the director of Business Development, CMC Services, at Frontage Laboratories. Image courtesy of Frontage Laboratories.

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The World Health Organization (WHO) announced on Oct. 29, 2024 that it has activated the Global Health Emergency Corp (GHEC) in collaboration with Member States and other partners in response to mpox outbreaks (1). This is the first time GHEC, which was established by WHO in 2023 as a response to COVID-19, has been activated to support countries dealing with mpox. Leaders from affected and other countries met on October 22 as part of the GHEC activation to discuss effect control measures, best practices, and the coordination of efforts.

Mpox was declared as a public health emergency by WHO in August of 2024 (2). “The emergence of a new clade of mpox, its rapid spread in eastern DRC [Democratic Republic of the Congo], and the reporting of cases in several neighboring countries are very worrying. On top of outbreaks of other mpox clades in DRC and other countries in Africa, it’s clear that a coordinated international response is needed to stop these outbreaks and save lives,” WHO Director-General Tedros Adhanom Ghebreyesus, PhD, said at the time of the announcement (2).

“WHO and partners are supporting the government of the Democratic Republic of the Congo and other countries to implement an integrated approach to case detection, contact tracing, targeted vaccination, clinical and home care, infection prevention and control, community engagement and mobilization, and specialized logistical support,” said Mike Ryan, MD, executive director of WHO’s Health Emergencies Programme, in the October 29 press release (1). “The GHEC enhances the ability of the many effective responders at national and regional levels to collaborate and ensure the success on the ground in interrupting transmission and reducing suffering.”

GHEC’s objective is to strengthen the response to health emergencies and provide a platform in which countries and health networks can collaborate the response, including deployment of experts and leaders. GHEC is assessing workforce capacities in eight countries including DRC and Burundi, which have been the most impacted by the mpox outbreak. There have been 22 areas identified by GHEC that are in need of epidemiology, surveillance, laboratory capacity, infection prevention, risk communication, and community engagement. WHO has deployed 55 experts to the impacted countries, as of October 17, that include WHO staff through the Global Outbreak Alert and Response Network (GOARN) and the African Volunteers Health Corps. GOARN is also mapping partner support on a bilateral basis to impacted countries and the coordination structure in the region, including providing experts, supplies, financial support, and strengthening capacity.

“By mobilizing trained professionals from within the continent, we ensure that responses are not only timely but also contextually relevant,” said Abdou Salam Gueye, MD, PhD, regional emergency director for the WHO Regional Office for Africa, in the press release (1). “The dedication and expertise of these responders are essential in saving lives and building resilient health systems capable of withstanding future threats.”

In other mpox news, a report based on outcomes of a workshop held on Oct. 2, 2024 by the International Coalition of Medicines Regulatory Authorities was announced by the European Medicines Agency on Oct. 25, 2024. The current epidemiological status and the availability of mpox vaccines in African countries was discussed during the workshop. Discussion at the workshop was focused on the prioritization of treatments for children because children are the most vulnerable group in the DRC and have the highest fatality ratio (3).

WHO. WHO and Partners Activate Global Health Emergency Corps for the First Time in Response to Mpox Outbreak. Press Release. Oct. 29, 2024.

WHO. WHO Director-General Declares Mpox Outbreak a Public Health Emergency of International Concern. Press Release. Aug. 14, 2024.

EMA. Fostering Regulatory Collaboration to Improve Access to Mpox Medicines. Press Release. Oct. 25, 2024.

Articles

WHO and its partners are providing support to countries dealing with mpox outbreaks.

WHO Activates Global Health Emergency Corp in Response to Mpox

Patrick Lavery is an Editor for the MJH Life Sciences brands 

. Previously at MJH, he filled the same role for 

AAPS PharmSci 360 2024: Big Data and Variation in Excipient Production

As part of its AAPS PharmSci 360 2024 coverage, 

 spoke with Pauline Janssen, global technical lead and product development manager at DFE Pharma, about her presentation at the conference, “Using Big Data Analysis to Better Characterize Excipient Variability,” delivered on Tuesday, Oct. 22, 2024.

Janssen said there is inevitable variation in all production processes, including excipient production, and big data sets can help—but especially when those analyzing the data are subject matter experts.

“We believe it's important to understand, what is the consistency? Which [data can] you look at [for] specific parameters, for example, inconsistency documents where you can see what is the typical variation that can be expected in a certain parameter?” Janssen said in the interview. “But a challenge when you want to evaluate multiple excipients, maybe multiple parameters, is actually all the potential interrelationships between those parameters. If you want to do a full evaluation of all these parameters and maybe perform a full design of experiments, you would require a huge amount of resources. And actually, this is also one of the key concepts in the QBD [quality by design] approach that allows [us] to identify what is the typical variation and what is the relevant variation in a large data set.”

Click the above video to watch the full interview.

AAPS PharmSci 360 was held from Oct. 20–23, 2024 in Salt Lake City, Utah. Find the rest of our coverage 

, and more information can be found on DFE Pharma's 

Pauline Janssen of DFE Pharma gave a presentation on the utility of analyzing big data sets to better understand and diagnose variability in the production process.

Feliza Mirasol is the science editor for 

Monte Rosa Therapeutics, a Boston, Mass.-headquartered clinical-stage biotechnology company specializing in novel molecular glue degrader (MGD)-based medicines, announced on Oct. 28, 2024,  that it entered into a global exclusive development and commercialization license agreement with Novartis. The agreement is worth potentially up to $2.1 billion and aims to advance vav guanine nucleotide exchange factor 1 (VAV1) MGDs, including MRT-6160, a drug candidate being evaluated in an ongoing Phase I single ascending dose (SAD)/multiple ascending dose (MAD) healthy volunteer study for immune-mediated conditions.

Under the agreement, Novartis will pay Monte Rosa $150 million up front in exchange for exclusive worldwide rights to develop, manufacture, and commercialize MRT-6160 and other VAV1 MGDs. Monte Rosa is eligible to receive up to $2.1 billion in development, regulatory, and sales milestones, starting with the initiation of Phase II clinical studies of MRT-6160. Monte Rosa is also eligible to receive tiered royalties on ex-US net sales.

Novartis will be responsible for all clinical development and commercialization of MRT-6160, starting at the Phase II clinical phase. Monte Rosa, meanwhile, will remain responsible for completing the ongoing Phase I clinical study for the drug candidate. In addition, Monte Rosa will co-fund any Phase III clinical development. The company will also share any profits and losses associated with the manufacturing and commercialization of MRT-6160 in the United States.

“We are thrilled to announce this agreement with Novartis, a key player in immune-mediated conditions, and we are excited about the transformative potential it provides for Monte Rosa and MRT-6160. We expect this will accelerate and broaden the scope of clinical development of MRT-6160 to advance this unique, orally bioavailable modality while retaining substantial value for Monte Rosa. We believe the transaction validates our unique and industry leading QuEEN discovery engine, and it further increases our conviction to rationally design and develop highly selective and safe MGDs for undruggable targets, including in the areas of immunology and inflammation, metabolism, and genetic diseases,” said Markus Warmuth, MD, chief executive officer, Monte Rosa Therapeutics, in a company press release. “The financial resources provided by this agreement are expected to extend our operational runway, enable us to advance our pipeline to potential value-creating milestones and anticipated proof-of-concept readouts, and further leverage our QuEEN discovery engine.”

MRT-6160 is a potent, highly selective, and orally bioavailable investigational degrader of VAV1, which is known as a key signaling protein found downstream of both T- and B-cell receptors. According to preclinical studies, MRT-6160 demonstrated deep degradation of VAV1, which resulted in a significant decrease in cytokines linked to immune-mediated conditions. It also showed no detectable effects on other proteins. The candidate has shown promising activity in preclinical models of multiple immune-mediated conditions (1,2).

"Novartis has had a long-standing interest in molecular glue degraders, which offer the potential to tackle challenging biological targets. We are excited about their application in immunology and the early progress we have seen by Monte Rosa in this space and with MRT-6160. We look forward to advancing MRT-6160 and learning more about its potential to provide a new therapeutic option for people living with a range of immune-mediated conditions,” said Fiona Marshall, president, Biomedical Research, Novartis, in the press release. “Novartis is committed to bringing forward new therapeutic options for these patients, and we are happy to be working with Monte Rosa to harness the potential of this approach to address unmet medical needs.”

1. Cartwright, A.; Desai, F.; Vora, S.; et al. MRT-6160, a VAV1-Directed Molecular Glue Degrader, Reduces Joint Inflammation and Autoantibody Production in a Collagen-Induced Arthritis Autoimmune Disease Model. Poster presented at Digestive Disease Week 2024, Washington, DC, May 21, 2024.
2.Cartwright, A.; Vora, S.; Gyger, L.; et al. MRT-6160, a VAV1-Directed Molecular Glue Degrader, Inhibits Disease Progression in a T-cell Transfer Mediated Colitis Model Concomitant with Reduced Calprotectin Expression. Poster presented at EULAR 2024—Annual European Congress of Rheumatology, Vienna, Austria, June 14, 2024.

The collaboration aims to advance clinical development of a Phase I drug candidate, MRT-6160, and to explore other therapeutic opportunities across multiple indications.

Novartis and Monte Rosa Therapeutics Form $2.1 Billion Global License Agreement for MGD-based Therapeutics

Arrow speed abstract blue background, communication data transfer technology concept. | Image Credit: ©Suppachok N

Emerging therapies and new modalities, such as cell and gene therapies (CGTs), have developed fast in the past decade. This ever-evolving development of not only new formulations but also new delivery methods has created an ever-complicated industry. Technology transfer is a critical step in drug manufacturing, specifically when contract manufacturers are involved.

 an efficient technology process ensures transferrable processes. “A well-defined and robust technology transfer process involves a systematic approach to transferring manufacturing processes, protocols, and knowledge from the research and development phase to the clinical and potentially commercial manufacturing setting” (1). “This process ensures the developed cell and/or gene therapy can be produced consistently, efficiently, and in compliance with regulatory requirements. The same requirements exist for transferring analytical methods to contract development and manufacturing organizations (CDMOs) or equivalent” (1).

“Tech transfer becomes more complex with emerging therapies and new modalities, particularly in method transfer, as these therapies are often derived from living cells, making consistency challenging to maintain,” says Satish Shetty, senior director, Product Development & Project Management, Halo Pharma (part of the Noramco Group). “Additionally, the manufacturing processes are highly intricate and rely on specific environmental and process conditions, which further complicates the transfer.”

Ahmed Youssef, senior manager USP, Process Development at Ascend, points to timing as being key for technology transfer with emerging therapies. “It takes an innovator around 12 to 24 months to make a product ready, tech transfer it, [and] complete the safety studies for it,” says Youssef. “But there could be other solutions that could be offered in the background that could make this more efficient, faster, and more attractive to product developers.”

Planning for technology transfer is essential, according to Hewitt 

 A smooth transfer requires careful evaluation, strategic decision making, and planning (1). Risk assessments are also crucial at this stage. “By proactively addressing these risks and implementing mitigation strategies during the initial assessment and planning stage, organizations can enhance the efficiency, reliability, and safety of the transfers” (1).

“A continuous feedback loop also encourages ongoing learning, incorporating insights from manufacturing teams into refining protocols. Regulatory alignment ensures compliance and adherence to guidelines. In essence, successful knowledge transfer ensures that the innovation harnessed in research is translated effectively, leading to consistent, high-quality outcomes in CGT manufacturing and accelerating the availability of transformative treatments to patients in need” (1).

Patient-centric therapies that might require small-batch manufacturing require flexible approaches to technology transfer, according to Andréa Simard, manager, Technical Services, Halo Pharma (part of the Noramco Group). This is particularly true for CDMOs that usually perform large-scale manufacturing. “Equipment train must be adjustable, and in-process control strategies should ensure process capability while meeting clinical or commercial needs,” Simard says. “Quality must be designed into the product through good knowledge of input materials and a robust manufacturing process, so that endpoint confirmation does not require extensive sampling and testing, which can greatly reduce the units available for the patients.”

However, Youssef remarks that tech transfer is a similar process no matter what batch size is involved. “Normally, when you tech transfer, you need to take risk-based approaches [and] appropriate measures to be able to tech transfer [a] process successfully and properly,” he says.

Brianna Kempfer, project manager at Sterling Pharma Solutions agrees. “The process of tech transfer is much the same, no matter the scale; a CDMO must evaluate the information provided: assessing any potential hazards, the scientific feasibility, and qualify the necessary synthetic and analytical methods. Through laboratory scale work, chemistry can be optimised and demonstrated to understand which parameters of the process are the most critical when scaling up and manufacturing.”

The smaller scale of patient-centric medicine production offers options for process development such as reagent and solvent choice, according to Kempfer. “Because of the smaller volumes of manufacturing, the costs of goods are usually higher, and so development of an efficient process that minimiszs potential losses in purification and isolation steps is crucial.”

One must understand technologies involved in formulation, as well, stresses Simard. “For example, formulation must consider patient-specific factors such as taste masking for bitter drugs or ease of administration for pediatric and geriatric populations,” she says. “Additionally, specialty packaging plays a crucial role in simplifying complex dosing regimens, making it easier for patients to adhere to treatment plans.”

Many bio/pharma outsourcing organizations have been moving to become full-service, end-to-end CDMOs. But does working with a contractor who offers services from every step of a drug’s lifecycle improve technology transfer. It depends, asserts Youssef. “If you mean by end to end, the whole process, from the start of plasmid manufacturing till commercial manufacturing of the batches and then the fill and finish and release, understand that the advantage would be that you're running all of that under one MSA [master supply agreement], one big MSA. But know that, not all CDMOs are expert and skilled in each unit operation when they offer the end-to-end process,” says Youssef.

Shetty points out that there are several reasons why tech transfer may be less complicated with an end-to-end service provider. “[A] unified sending unit (SU) and receiving unit (RU) enable seamless knowledge transfer. Tech transfers are often complicated by development knowledge getting lost through site transfers, and delays from having to set up project logistics at a new CDMO, so having both teams in the same organization is a solid advantage.”

End-to-end service providers often provide consistency in the equipment used between the different phases of development and manufacture, notes Shetty. There is also often the same project manager and core team involved, as well as the same excipient grades and reduced supply lead times. End-to-end providers also feature “fewer knowledge gaps and better identification of potential scale-up issues,” according to Shetty. “Consolidating R&D and supply chain expertise minimizes logistical delays and fosters smoother transitions, troubleshooting, and overall customer experience,” Shetty concludes.

“When scaling up between clinical phases and commercial launch, it is common for a process to move between sites, and potentially between countries, within an end-to-end provider, so this results in the need for a tech transfer. Whether this is an internal or external transfer, there is little difference in the process that needs to be undertaken,” says Kempfer.

When it comes to sponsors and contract organizations working together to ensure a secure tech transfer, Youssef specifies that the CDMO should shoulder the responsibility. “A good CDMO [should] have structured communication, because communication is key … when you're talking to your business partner. We always build that in a more collaborative environment,” says Youssef. “[A CDMO needs] to protect the IP [intellectual property] rights of their clients, their partners, as well as good documentation practices, in addition to a solid IT department. All of that gives the assurance to the security of the data and the security of the transfer information between the CDMO and their partner.”

Simard stresses that communication is key for secure tech transfer. “The first step is to define success criteria and core values, ensuring both parties have a mutual understanding of each other's capabilities, limitations, and the project's critical milestones. When issues arise, they should be treated with speed and transparency in an atmosphere fostering collaboration rather than finger-pointing, so that solutions and a path forward may be found as a team,” Simard says.

Expectations, milestones, goals, and needed processes should be communicated and understood, says Kempfer. “The more information that can be shared at the start will reduce the potential of unexpected problems; however, having a transparent relationship between parties, where communication is open will allow progress to be monitored, and any issues that do arise to be shared and understood as quickly as possible. Having a key point of contact within the CDMO who can liaise with all of the key members of the project team across multiple disciplines, allows a customer to gain direct access to progress and ensure that communication is as efficient as possible,” Kempfer states.

Trust and transparency should be established, confirms Shetty. Differences in facilities and excipients should be understood, and process documentation should be simplified. “[One should] ensure regular communication between subject matter experts, rather than relying solely on project managers,” Shetty summarizes. “[Sponsors and contractors should] proactively work as a team to identify and resolve potential issues [and] focus on a common goal that benefits both parties.”



1. Hewitt, M.; Bellot, L.; Anderson, C. Best Practice Tech Transfer Methods for CGTs. 

Emerging therapies, patient-centric medicines, and the ever-changing world of bio/pharmaceuticals complicate technology transfer.

Tech Transfer in the New World of New Modalities

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In a press release on Oct. 24, 2024, the contract research, development, and manufacturing organization (CRDMO) BioDuro-Sundia, headquartered in Irvine, Calif., said it was launching a new, pilot-scale production laboratory that will enable scale-up synthesis for drug substance from 500 grams to kilograms (1). The laboratory is located at BioDuro-Sundia’s R&D campus in the Free-Trade Zone of Shanghai, China.

The kilo laboratory, according to BioDuro-Sundia, is equipped with large-capacity reactors allowing the company to simultaneously conduct multiple synthesis batches, in the interest of improving operational efficiency (1). Other key equipment includes both high- and low-temperature jacketed reactors, low-temperature spherical reactors, and advanced safety evaluation instruments—among them, differential scanning calorimetry, which collects safety data that informs the development of safe, efficient reaction routes, the press release said.

"Our new kilogram laboratory exemplifies BioDuro-Sundia's unwavering commitment to advancing our CRDMO platform and delivering exceptional value to our global partners," said Armin Spura, PhD, CEO of BioDuro-Sundia, in the press release (1). "This state-of-the-art facility enables us to scale up production with greater speed and flexibility, expediting the journey of drug candidates from discovery to the clinic, and ultimately helping to address critical unmet medical needs."

Taken as a whole, BioDuro-Sundia said, the features of the kilo laboratory are designed to support complex, multi-step scale-up reactions of select APIs as well as advanced intermediates (1). The company said that as the demands of its partners continue to grow, the opening of the laboratory enhances BioDuro-Sundia’s ability to accelerate a greater number of drug candidates and, as Spura said, to do so from discovery through preclinical and clinical phases, building a bridge between medicinal chemistry research and process development.

The new kilo laboratory is on the same site as BioDuro-Sundia’s Compound Management Center, the launch of which was announced earlier in October 2024 (2). With real-time temperature and humidity controls, the center has the ability to manage more than 400,000 compounds, either solid or liquid, and is equipped with a liquid handling station for fully automated workflows, while sample management software tracks steps at every point of the lifecycle. Services able to be offered include storage, weighing, dissolution, plating, liquid chromatography–mass spectrometry (LC–MS) analysis, and distribution.

 spoke with Kevin Li, MBA, about BioDuro-Sundia’s role in the area of integrated services, and the benefits such services can provide to pharma companies.

“One side can handle both drug substance and drug product, and one side can handle the pre-formulation, formulation development, until commercial manufacturing, everything in one side,” Li said in the interview, “so that integrated solution can really help customers to accelerate their innovation through multiple benefits” (3).

1. BioDuro-Sundia. BioDuro-Sundia Launches New Kilogram Laboratory to Speed Development from Discovery to Preclinical and Clinical Phases. Press Release. Oct. 24, 2024.
2. BioDuro-Sundia. BioDuro-Sundia Launches New Compound Management Center, Strengthening Drug Discovery Services. Press Release. Oct. 2, 2024.
3. Thomas, F. 

CPHI Milan 2024: Highlighting the Benefits of Integrated Services.

The laboratory is on the same site as BioDuro-Sundia’s new Compound Management Center, which was launched earlier in October 2024.

BioDuro-Sundia Opens New Kilogram Laboratory at Shanghai Site

The European Medicines Agency (EMA) announced on Oct. 25, 2024 that international regulators have published a report based on outcomes of a workshop held on Oct. 2, 2024 by the International Coalition of Medicines Regulatory Authorities (ICMRA) (1). The workshop, which was held virtually, included representatives from international medicine regulatory authorities, such as FDA, EMA, and the Japan Pharmaceuticals and Medical Devices Agency, and the World Health Organization (WHO) to discuss access to mpox medicines during an outbreak. WHO declared mpox a public health emergency of international concern in August 2024.

The current epidemiological status and the availability of mpox vaccines in African countries was discussed during the workshop. The use of mpox vaccines in pregnant people and in children was also discussed, specifically efforts to fill the gap of evidence for these patient groups. Attendees also discussed effectiveness surveillance systems and regulatory pathways for mpox vaccine and drug approvals. The need for large clinical trials was emphasized by participants so that the appropriate evidence may be generated to quickly develop and approve these medicines.

“One of the major challenges during these outbreaks has been the unequal availability of medical interventions, such as antivirals and vaccines, with low-income countries in Africa facing the greatest difficulties. While high-income countries were able to access vaccines more readily, African countries, where mpox is endemic, have struggled with delayed regulatory approvals and inaccessible prices,” the report states (2).

According to the report, children are the most vulnerable group in the Democratic Republic of Congo and have the highest fatality ratio. Because of this, the workshop discussion prioritized pediatric treatments. FDA granted emergency use authorization for the MVA-BN vaccine for children; this vaccine has been used in the United States safely. Canada has authorized the vaccine for people 18 or older but has made a discretionary recommendation for use in children. EMA expanded the indication for the vaccine to be used in children 12 to 17 years old.

“There is limited evidence for the use of MVA-BN vaccine in pediatric populations under 12 years of age; the safety profile is however not expected to be different in this population. The WHO Strategic Advisory Group of Experts on Immunization has also recommended that the MVA-BN vaccine can be used in children if the benefits outweigh the risks,” the report states (2). “For these reasons, regulators within ICMRA stand ready to support decisions in countries most affected, including for use in children less than 12 years of age. However, misinformation is of concern and robust communication strategies need to be implemented.”

During the workshop it was recommended that a dose-sparing strategy using the intradermal route of administration be considered due to the gaps in the vaccine supply and the number of doses that are needed for high impacted countries. It was also recommended that a different vaccine, LC16m8, be considered, as it is currently approved for use in all age groups in Japan.

New vaccine development discussion brought to attention the different regulatory pathways for approval and that alternatives to placebo-controlled studies should be considered, as well as alternative methods of administration.

“ICMRA unanimously agreed that fragmentation in clinical research, as has happened so far with mpox, must be avoided, as studies need to be conducted rapidly and efficiently in the best interest of patients. More collaboration towards merging efforts from investigators into larger unified clinical trials is advocated,” the report states.

ICMRA. Summary Report of the International Coalition of Medicines Regulatory Authorities (ICMRA) Workshop on Mpox, October 2, 2024. 

https://www.icmra.info/drupal/news/mpox_news_announcement_25oct2024/mpox_ws_report_2oct2024

The report highlights international regulators’ plans for the development and availability of vaccines to prevent and drugs to treat mpox.

Regulatory Collaboration on Mpox Treatments Summarized in Report

FDA has approved the AbbVie treatment Vyalev (foscarbidopa and foslevodopa) for use in adult patients with advanced Parkinson’s disease, AbbVie announced in a press release on Oct. 17, 2024 (1). The approval makes Vyalev the first and only subcutaneous, 24-hour infusion of levodopa-based therapy for treatment of motor fluctuations in these patients in the United States.

"People living with advanced Parkinson's disease experience daily challenges as a result of uncertainty in managing motor fluctuations, especially as their disease progresses," said Roopal Thakkar, MD, executive vice president, research & development, and chief scientific officer, AbbVie, in the release (1). "We are proud to bring this innovation to patients who may benefit from motor symptom control through continuous 24-hour administration of Vyalev."

Onset of motor complications, according to AbbVie, can be due to neuronal degeneration as well as fluctuating levodopa levels in plasma, with 50% of patients reporting these symptoms anywhere from two to five years after diagnosis, and from 80% up to 100% presenting with them after a period of 10 years (1). Dyskinesia, or involuntary movement, is another hallmark of Parkinson’s disease attributable to these factors.

A 12-week, Phase III trial that studied continuous, subcutaneous infusion of Vyalev against oral immediate-release carbidopa/levodopa (CD/LD IR), the findings of which were disclosed in 

 in 2022, informed FDA’s decision, according to AbbVie (1). Patients were measured in “on” time, when symptoms are generally well controlled, to “off,” when tremor and stiffness may reappear, and in the study, the increase in “on” time without troublesome dyskinesia was 2.72 hours at week 12 with Vyalev, and 0.97 hours with CD/LD IR (2).

Adverse reactions were shown to be mostly mild to moderate and non-serious, with the most frequent being infusion site events, hallucinations, and dyskinesia (1).

"For too long, the Parkinson's community has had limited treatment options for advanced disease. Due to the progressive nature of the disease, oral medications are eventually no longer as effective at motor symptom control and surgical treatment may be required," said Robert A. Hauser, MD, professor of neurology and director of the Parkinson's and Movement Disorder Center at the University of South Florida, in the press release. "This new, non-surgical regimen provides continuous delivery of levodopa morning, day and night."

Vyalev is also marketed under the brand name Produodopa and has been approved in 35 countries, with AbbVie saying it is continuing to work with regulatory authorities around the world to broaden the therapy’s scope to more adults with advanced Parkinson’s disease. So far, the company says, more than 4200 patients globally have begun treatment with Vyalev (1).

In the US, coverage of Vyalev for Medicare patients is expected to start in the second half of 2025 (1).

1. AbbVie. U.S. FDA Approves VYALEV (foscarbidopa and foslevodopa) for Adults Living with Advanced Parkinson's Disease. Press Release. Oct. 17, 2024.
2. Soileau, M.J.; Aldred, J.; Budur, K.; et al. Safety and Efficacy of Continuous Subcutaneous Foslevodopa-Foscarbidopa in Patients with Advanced Parkinson's Disease: A Randomised, Double-Blind, Active-Controlled, Phase 3 Trial. 

Vyalev, also known as Produodopa, has been approved in 35 countries, with more than 4200 patients having started treatment.

FDA Approves AbbVie Therapy for Adults with Advanced Parkinson’s Disease

Science laboratory test tubes, laboratory equipment | Image Credit: © BillionPhotos.com - © BillionPhotos.com - stock.adobe.com

Modifi Biosciences, a company formed in 2021 as a spinout of technology developed at Yale University, announced on Oct. 23, 2024 that it is being acquired by Merck, known as MSD outside of the United States and Canada (1). Modifi Biosciences develops direct DNA modification enabled cancer treatments. The novel class of small molecules target a DNA repair protein called O6-methylguanine methyl transferase (MGMT). The company’s research was published in 

in 2022 (2) and has had pre-clinical data amassed through a number of tumor models, including patient-derived xenograft models of gliomas.

“In founding Modifi Biosciences, we sought to radically change the oncology treatment paradigm for cancer patients with glioblastoma and other tumors,” said Ranjit S. Bindra, MD, PhD, Modifi Biosciences co-founder, Harvey and Kate Cushing, professor of Therapeutic Radiology at Yale School of Medicine, and scientific director of the Yale Brain Tumor Center at Smilow Cancer Hospital, in a press release. “We are honored to have Merck recognize the potential of our science, and as an oncology company, they are perfectly positioned to advance our innovations through clinical trials and commercialization.”

“DNA repair defects are a frequent hallmark of tumor cells and a major cause of resistance to cancer therapy,” said David Weinstock, MD, vice-president, discovery oncology, Merck Research Laboratories, in the release. “The talented Modifi Biosciences team has developed an innovative approach that we believe has potential for treating some of the most refractory cancer types.”

“We designed our small molecules to have the ability to uniquely overcome clinical resistance mechanisms that have been known for decades but until now have been non-actionable. Additionally, we created the molecules in a manner which allows them to be rapidly progressed from bench-to-bedside,” said Seth Herzon, PhD, Modifi Biosciences co-founder and the Milton Harris ’29 PhD Professor of Chemistry in Yale’s Faculty of Arts and Sciences and professor of Pharmacology and Therapeutic Radiology at the Yale School of Medicine, in the release.

The acquisition agreement has Merck, through a subsidiary, taking possession of all outstanding shares of the company for $30 million with potential milestone payments up to $1.3 billion.

In other news by Merck, the company entered into a license and collaboration agreement in October with Mestag Therapetuics, a Cambridge, UK-based biotech company to identify novel targets for inflammatory disease treatments, using Mestag’s reversing activated fibroblast technology platform. The proprietary platform models the pathogenic role of fibroblasts in human disease.

“Mestag was founded on … insights into fibroblast–immune biology, and as an early innovator in this area of research, we have built a robust pipeline of antibody programs and created a unique and productive target discovery platform,” said Susan Hill, PhD, chief executive officer of Mestag, in a company press release (3). “We are acutely aware of the significant unmet needs faced on a daily basis by patients suffering from inflammatory diseases. We are thrilled to collaborate with [Merck], together driving continued innovation for the benefit of patients.”

Modifi Biosciences. Modifi Biosciences Acquired by Merck. Press Release. Oct. 23, 2024.

Lin, K.; Gueble, S.E.; Sundaram, R.K.; Huseman, E.D.; Bindra, R.S.; Herzon, S.B. Mechanism-based Design of Agents that Selectively Target Drug-resistant Glioma. 

Mestag Therapeutics. Mestag Therapeutics Announces License and Research Collaboration with MSD to Identify Novel Targets for Inflammatory Diseases. Press Release. Oct. 8, 2024.

Merck is acquiring the Yale-spinout, which develops direct DNA modification-enabled cancer treatments. 

Merck Acquires Modifi Biosciences

Leaders in pharmaceutical industry discuss the latest news making waves in the pharmaceutical industry. 

Behind the Headlines, Episode 5: GLP-1 Shortage, Nobel Prize, RNA Editing, and More

 is a bi-weekly panel discussion examining the latest trends, readouts, and other factors that drive pharmaceutical news and innovation. Each episode features consultants, venture capitalists, scientists, patient advocates, and journalists discussing the prior weeks’ top news while seeking to highlight the more enduring lessons that hide behind the headlines.

In episode 5, panelists Laks Pernenkil, Principal Life Sciences at Deloitte; Brian Feth, CEO at Xcell Biosciences; and Alex Philippidis, Senior Business Editor at Genetic Engineering & Biotechnology News, go behind the headlines to understand why FDA felt it was time to remove 

 from the drug shortages list (1) and how Catalent’s sale of a small molecule manufacturing facility (and incidentally its own headquarters) to expanding European company Ardena might affect future drug availability (2).

The panel also discussed Nobel Prize awards being given in the 

 field (3) and what that might mean in terms of growth, given a series of false starts and hurdles including the shelving of a hepatitis C therapy due to fears that microRNA might not compete commercially with traditional therapeutic approaches (4). The Nobel Prize in physics awarded to recognize advancements in artificial intelligence (5) was likewise considered from the perspective of how AI will bolster drug discovery and drug formulation, as well as help optimize drug manufacturing. 

Lastly, panelists discussed the emerging potential for novel protein replacement therapies on the heels of Wave Life Sciences’ positive clinical data for RNA editing to combat AAT protein deficiency (6), and how temporary and reversible RNA-editing approaches may confer additional benefits that further support this novel approach in the marketplace.

FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize. FDA Drug Safety and Availability. October 2, 2024. 

https://www.fda.gov/drugs/drug-safety-and-availability/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize

Catalent signs agreement to sell Somerset, NJ oral solids facility. Catalent. October 14, 2024. 

https://www.catalent.com/catalent-news/catalent-signs-agreement-to-sell-somerset-nj-oral-solids-facility/

The Nobel Prize in physiology or medicine, 2024. 

https://www.nobelprize.org/prizes/medicine/2024/press-release/

Sparmann A and Vogel J. RNA-based medicine: from molecular mechanisms to therapy. 

https://www.nobelprize.org/prizes/physics/2024/press-release/

Wave Life Sciences Announces First-Ever Therapeutic RNA Editing in Humans Achieved in RestorAATion-2 Trial of WVE-006 in Alpha-1 Antitrypsin Deficiency. Press release. Wave Life Sciences. October 16, 2024. 

https://ir.wavelifesciences.com/news-releases/news-release-details/wave-life-sciences-announces-first-ever-therapeutic-rna-editing

Laks Pernenkil, Brian Feth, and Alex Philippidis go behind the headlines to discuss the impact of recent news, including FDA’s drug shortage list update, Nobel prize winners in microRNA and AI, and a big-potential research win for RNA editing. 

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