Merck and Pfizer Inc. announced that the US Food and Drug Administration (FDA) has accepted for Priority Review the supplemental Biologics License Application (sBLA) for Bavencio (avelumab) in combination with Inlyta (axitinib)* for patients with advanced renal cell carcinoma (RCC). The application has been given a target action date in June 2019.
“The combination of Bavencio with Inlyta builds on Pfizer’s significant heritage in advancing standards of care for patients with advanced RCC and has the potential to make a meaningful impact for the lives of patients. We look forward to working with the FDA to bring this potential new treatment option to patients as quickly as possible.”
Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development
“Our alliance is focused on the development of potential new treatment options for patients with cancers that have high unmet medical needs, including the broad spectrum of people living with advanced RCC,” said Luciano Rossetti, M.D., Executive Vice President, Head of Global Research & Development at the Biopharma business of Merck. “This regulatory milestone, which closely follows the acceptance of our application in Japan, represents an important step forward for science and for patients.”
The submission is based on data from the pivotal Phase III Javelin Renal 101 trial, which were presented in a Presidential Symposium at the European Society of Medical Oncology (ESMO) 2018 Congress in Munich. In December 2017, the FDA granted Breakthrough Therapy Designation for Bavencio in combination with Inlyta for treatment-naïve patients with advanced RCC.
Despite available therapies, the outlook for patients with advanced RCC remains poor.1 Approximately 20% to 30% of patients are first diagnosed at the metastatic stage.2 The five-year survival rate for patients with metastatic RCC is approximately 12%.
The clinical development program for avelumab, known as Javelin, involves at least 30 clinical programs and more than 9,000 patients evaluated across more than 15 different tumor types. In addition to RCC, these tumor types include breast, gastric/gastro-esophageal junction, and head and neck cancers, Merkel cell carcinoma, non-small cell lung cancer, and urothelial carcinoma.
*The combination of Bavencio and Inlyta is under clinical investigation for advanced RCC, and there is no guarantee this combination will be approved for advanced RCC by any health authority worldwide. In the US, Inlyta is approved as monotherapy for the treatment of advanced RCC after failure of one prior systemic therapy. Inlyta is also approved by the European Medicines Agency (EMA) for use in the EU in adult patients with advanced RCC after failure of prior treatment with Sutent (sunitinib) or a cytokine.
New data strengthening the continued clinical development of NeuroRestore ACD856
AlzeCure Pharma, a pharmaceutical company that develops a broad portfolio of small molecule candidate drugs for diseases affecting the central nervous system, with projects in both Alzheimer’s disease and pain, today announced that the company’s presentations at the scientific conference CTAD 2022 are now available in their entirety on AlzeCure’s website. They include new clinical and preclinical data with the company’s leading drug candidate NeuroRestore ACD856, which is being developed with a focus on Alzheimer’s disease
The abstracts, titled Quantitative EEG results from a multiple ascending dose study in healthy volunteers with NeuroRestore ACD856, a positive modulator of Neurotrophin Trk-receptors, and Preclinical characterization of ACD856, a cognitive enhancer in clinical development for the treatment of cognitive dysfunction in Alzheimer’s disease, demonstrates increased plasticity, neuroprotection and a possible disease modifying effect, were presented by Johan Sandin, CSO, and Martin Jönsson, CEO at AlzeCure Pharma. The results include new clinical and preclinical data with ACD856, the lead drug candidate in the NeuroRestore project.
The clinical data come from the recently completed phase I MAD study, where the substance, in addition to good safety and tolerability, was also shown to cross the blood-brain barrier effectively and in relevant quantities. The new EEG data, which measures brain activity, also showed that ACD856 activates relevant neuronal pathways in the brain with relevance for cognition and depression, something that strengthens the continued clinical development of the substance.
In addition to memory-enhancing and symptom-relieving properties, the preclinical data presented show that ACD856, also has potentially disease-modifying properties with both neurorestorative and neuroprotective properties. The substance also shows positive long-term effects after repeated administration, which indicates an enhanced plasticity in relevant neuronal pathways.
A positive modulator of both NGF/TrkA- and BDNF/TrkB-mediated signaling, ACD856 has been shown in preclinical studies to improve cognition and memory and is poised for Phase 2 clinical trials, where it is being developed primarily for the treatment of Alzheimer’s disease.
“These new positive results with ACD856 support the continued clinical development of the substance in both cognitive disorders and depression. The fact that we also see neuroprotective effects of the substance is something that can further strengthen external interest in the project,” said Johan Sandin, CSO at AlzeCure Pharma.
“This is very good news and development that adds to the previous positive data for ACD856 and further strengthens our commercial opportunities for this promising compound,” said Martin Jönsson, CEO of AlzeCure Pharma AB.
Optimize Tech Transfer and Industrialization
Sanofi will use Dassault Systèmes’ “Made to Cure for BioPharma” industry solution experience based on the 3DEXPERIENCE platform to design, implement, qualify and operate modular production lines at the two “EVolutive Facilities.” These will rely on single-use technology and mobile equipment to manufacture up to four products simultaneously and sustainably by selecting the most advanced technologies to reduce their energy consumption. The platform provides a virtual environment for collaborative innovation and end-to-end data management across the life cycle. Sanofi can experience the manufacturing systems under development and their operation virtually and optimize scale up and industrialization processes before deploying them.
“We want to improve people’s lives by giving them faster access to vaccines and treatments while minimizing the environmental impacts of our activities,” said Ana Alves, EVolutive Facility Global Project Head & Site Head of Neuville sur Saone, Sanofi. “Dassault Systèmes delivers the technology we need to accelerate the introduction of new products in the facility by supporting the collaborative works of our teams and by strengthening the standardization of designs and models. It will also bring capabilities to reach our objective to produce several products in the EVF in an optimized schedule, thanks to the digital twin. Then, the 3DEXPERIENCE platform will help us to address the complexity of the product lifecycle management in a highly regulated environment and for the benefit of our patients.”
Pharmaceutical manufacturers must qualify facilities, equipment and processes before production to ensure safety and quality. This can take weeks or months depending on the equipment configurations and process parameters for different product recipes. Virtual twins enable manufacturers to standardize modules, reduce this timeframe, and boost their ability to quickly and massively produce crucial therapies.
With a virtual twin, Sanofi can visualize and simulate the recipe, equipment and consumables that a particular process requires, as well as the flow and activity of the modules and operators in the “ballroom” – a flexible and adaptable area that enables manufacturers to quickly switch between processes. Sanofi can add, remove and replace functional elements and process steps as needed in a seamless way, and reconfigure the production lines for a fast changeover from one product to another one. It can also accelerate the main activities of the life cycle of new modules, processes and facilities more quickly and catalog them into its product life cycle management for reuse and faster product changeover.
“The pandemic made it clear: BioPharmas must be able to maximize efficiency and quickly provide high-quality, innovative therapeutics to patients worldwide,” said Claire Biot, Vice President, Life Sciences & Healthcare Industry, Dassault Systèmes. “Sanofi is responding to this challenge with next generation modular manufacturing that can transform the speed at which products reach patients. Thanks to the 3DEXPERIENCE platform, Sanofi will implement new products right the first time, with faster production ramp-ups and concurrent process production for built-in flexibility. Ergonomics on the shop floor can be simulated and improved.”
Pharmacode Data Check for Medication Packaging
Pharmaceutical packaging is a sophisticated and multi-staged process that involves machines and humans diligently working side by side. The packaging process consists of more than 20 steps, and each is very complex.
Critical steps include:
- physically separating products to avoid mixing-up finished and unfinished items.
- multiple checks to ensure that medicines conform to the descriptions given in the product’s batch manufacturing record (BMR).
- identification of packaging that contains relevant medical instructions.
- eliminating excess materials.
- random testing and much more.
However, pharmaceutical factories are frenetic. Workloads can be overwhelming because multiple production lines simultaneously churn, producing or packaging anywhere from 10–100 different medications. The environment’s frenzied nature also can trigger human error at any stage. External factors, such as labor shortages, can also hinder medication packaging.
Therefore, factories must take extra steps when mistake-proofing packaging lines. After all, protecting product safety and a company’s reputation (along with revenue) cannot be underemphasized because human lives are literally on the line. For instance, in 2013, French authorities discovered that zopiclone (a sleeping pill for insomniacs) was discovered in packages of furosemide diuretics. Police investigated deaths possibly linked to the improperly packaged medication, and a large-scale recall was issued.
Given the consequences of improperly labeled or packaged medication, Job #1 is ensuring that the correct medicine and associated instructions are placed in the corresponding packaging. Doing so correctly ensures drug packaging compliance, and it’s precisely where Germany’s Elmicron GmbH steps in to help.
ISO: In Search Of Quality
Elmicron’s specialty lies in barcodes, data matrix codes, and RFID technology for labeling and identification.
“We are the pioneers who helped develop barcode technology and standardize it within Europe’s certification societies,” beams Dr. Harald Oehlmann, Elmicron’s managing director.
Furthermore, thanks to extensive practical experience and a team of high-profile experts, Elmicron has implemented cross-industry and value-added concepts for several of Europe’s top businesses. Given Elmicron’s mission to help customers ensure accuracy via automatische datenkommunikation (automatic data communication), it is fitting that the company worked to earn an ISO 9001 quality management certification.
Carrying ISO 9001 demonstrates Elmicron’s commitment to providing high-quality products that meet both customer quality and regulatory requirements while validating Elmicron’s system for use by integrators and at the customer’s site. Lastly, the ISO 9001 certification verifies that Elmicron’s experts understand the intricacies of quality management systems and corporate governance—exactly what pharmaceutical firms need to maintain product quality and their good standings.
The Dr. Prescribes the Pharmacode Data Check Inspection System
The pharmaceutical industry’s packaging plights caught Dr. Oehlmann’s attention, inspiring him and his team to develop Elmicron’s Pharmacode Data Check inspection system. The system consists of proprietary Elmicron software running on an industrial-grade Noax touchscreen computer. Data capture occurs with Code Corporation’s CR5000 Barcode Reader to read PHARMA-CODE—a highly specialized, and often color-keyed, barcode type used in pharmaceutical packaging.
A trademark of Laetus, PHARMA-CODE prevents the intermixing of medication packaging. A specific PHARMA-CODE correlates to a specific medication, such as an antibiotic. This code is then assigned to every part of the medication’s packaging (for example instructions, labels, blister packs, and contraindication info). IT systems manufacturers, such as Elmicron, then create validation solutions.
With a firmly cemented foundation thanks to their barcode standardization work, a chance technical support request united Elmicron and Code.
“In the early 2000s, Elmicron [via US-based Omnitron Systems, a network connectivity specialist] received the task for technical support in Europe from an overseas client,” recalls Dr. Oehlmann.
The support contract was linked to Code Corp., and after their initial project, a partnership solidified.
“We have been working with Code for decades, and they’ve consistently proven their reliability in terms of high quality and good service,” reflects Dr. Oehlmann. “Our joint work has developed into a successful, long-term partnership. So when the need for Pharmacode Data Check arose, Code’s CR5000 was our first choice since we trust Code products. They provided us with a suitable device for our project.”
As Dr. Oehlmann recollects, early during development, Elmicron’s team mandated that the CR5000 must provide rapid barcode scanning. Additionally, the scanner had to read the same barcode multiple times with a brief break between scans, all while supporting hands-free workflows. Code reps demonstrated that the CR5000 met Elmicron’s needs during product evaluation, attracting the attention of developers.
Integration began, and the firm relabeled the CR5000 as Elmicron Model ECR 5210 linear & 2D, “Pharmacode Data Check configuration.” Beyond their essential requirements, the developers discovered additional CR5000 features and functions that would give Elmicron’s system additional flexibility. For instance, the barcode reader provides Pharmacode Data Check support and presentation mode, as well as manual and automatic scanning.
The savvy integration of industrial- and enterprise-grade components has given the Pharmacode Data Check inspection system a fair degree of customization. Thus, Elmicron has modified the system for deployment in automotive production, electronics, tobacco, consumer packaged goods, and the marine sector, among others.
The Challenge: Problems Perfectly Packing Pills
Given the importance of the system’s mission, flawless performance was a must. However, Code and Elmicron faced two challenges during system development:
- The Pharmacode Data Check device would unexpectedly reboot, stopping barcode scanning, which necessitated troubleshooting because a missed scan during packaging would lead to mistakes. Code’s tech support team had this sorted out within four weeks.
- Quick re-scan prevention of the same code had to be disabled by configuration codes.
“We would advise anyone who requires a barcode scanner solution, both hardware or software, to use the full capability of Code’s solutions,” encourages Dr. Oehlmann.
The Results: Growing Demand for Quality Assurance
Elmicron’s Pharmacode Data Check Inspection System is enjoying demand across Europe because it hits the goals of:
- Quality assurance through error detection and avoidance.
- Simple operation.
- Integrated functionality and automation.
Moreover, Elmicron’s customers can guarantee 100 percent control of the medical packaging process, giving them a decisive advantage over competing firms.