Daria G. Husni

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

On Oct. 5, 2023, Kyowa Kirin Co, a biotechnological pharmaceutical company based in Japan, announced that it plans to acquire Orchard Therapeutics, a “global gene therapy leader” based in London, for approximately $477.6 million. Orchard’s history of developing and commercializing therapies for rare diseases will serve to enrich Kyowa Kirin’s growing portfolio and aligns with the company’s vision to “consistently create and deliver medicines with life-changing value that ultimately makes people smile, as a J-GSP.” Kyowa Kirin’s focus is on areas of great unmet need, and it is pursuing cell and gene therapies in order to meet that need head-on.

Among Orchard Therapeutics’ portfolio is Libmeldy (atidarsagene autotemcel), also known as OTL-200, which is intended for patients with early-onset metachromatic leukodystrophy (MLD), a rare and life-threatening metabolic disease. It has been approved by the European Commission and UK Medicines and Healthcare products Regulatory Agency to treat late infantile and early juvenile patients with MLD. Currently, it is under Priority Review by FDA with a Prescription Drug User Fee Act goal date of March 18, 2024.

Orchard Therapeutics is also developing two clinical-stage programs, OTL-203 and OTL-201, to treat mucopolysaccharidosis type I or Hurler’s syndrome (MPS-IH) and mucopolysaccharidosis type IIIA (MPS-IIIA) or Sanfilippo syndrome. Both syndromes are severe pediatric neurometabolic disorders. Orchard also has several early research programs, including treatment for a severe, genetic form of Crohn’s disease and frontotemporal dementia that Kyowa Kirin plans to advance.

By combining Orchard’s HSC gene therapy platform technology with its own resources and abilities, Kyowa Kirin hopes to continue development of many biopharmaceutical candidates that have the potential to give life changing medical care, especially in Kyowa Kirin’s most experienced areas, such as oncology and autoimmune diseases.

Articles

The Japanese biotech company plans to make good use of Orchard’s portfolio, furthering its goal of providing life-changing medical care through cell and gene therapy.

Kyowa Kirin Set to Acquire Orchard Therapeutics for $477.6 million

Text sign showing Industry News. Business photo text delivering news to the general public or a target public | Image Credit: © Artur - stock.adobe.com

On Sept 29, 2023, FDA announced a pilot program, Support for clinical Trials Advancing Rare disease Therapeutics (START), intended to support development of novel drug and biological products for rare diseases. The agency is establishing a pilot program for a limited number of sponsors, intended to allow for more regular communication with FDA on addressing clinical development issues. Selected participants will have access to FDA advice and pertinent communication for product-specific development issues such as choice of control group, clinical study design, and fine-tuning the choice of patient population.

To be eligible for the program, participants must be sponsors of products in clinical trials under an active Investigational New Drug application (IND) and regulated by the Center for Biologics Evaluation and Research (CBER) and/or the Center for Drug Evaluation and Research (CDER). The requirements for eligibility for the program differ between CBER and CDER-regulated products. CBER-regulated products must be a gene or cellular therapy being developed as treatment for a currently untreatable rare or serious condition that can lead to significant or death within the first 10 years of life. CDER requires that products be intended to treat rare neurodegenerative conditions, such as those of rare genetic metabolic type.

Applications for the START program will be open between Jan. 2, 2024, and March 1, 2023. Sponsors who show the ability to push their development program forward towards a marketing application will be more likely to be selected. FDA will choose up to three participants for each center. After an appraisal of this pilot program and feedback from participating sponsors, FDA may announce a second iteration, which will be announced at a later date. Participation will finish when the development program has reached a notable regulatory landmark, such as reaching the stage before submitting a marketing application or launch of the pivotal clinical study stage.

The START program is not the only FDA resource available to sponsors of therapies for rare diseases. FDA recently published a 

, intended for stakeholders to give feedback on challenges and opportunities relating to cellular and gene therapies intended to treat rare diseases. It also published a docket for stakeholder feedback under the CEDER Accelerating Rare disease program. This docket will allow FDA to find knowledge gaps in rare disease drug development, and develop public resources on regulatory issues surrounding clinical trial design.

The program will allow sponsors of certain CBER and/or CDER-regulated products more frequent communication with FDA staff.

FDA Establishes Pilot Program to Accelerate Rare Disease Therapy Development

TOP NEWS on grunge world map | Image Credit: © Sean K - stock.adobe.com

On Oct. 2, 2023, The Nobel Prize in Physiology or Medicine was awarded jointly to Katalin Karikó and Drew Weissman for their work on nucleoside base modifications that allowed the development of effective messenger RNA (mRNA) vaccines against COVID-19. The duo’s groundbreaking discoveries were crucial in the current international understanding of how mRNA interacts with the immune system; their work played a crucial role in the rapid rate of vaccine development during the global pandemic.

Karikó and Weissman began their collaboration during the 1990s at the University of Pennsylvania. Karikó, then an assistant professor, was committed to developing mRNA as a therapeutic, despite difficulties in receiving funding. Enthusiasm for mRNA research was limited at the time; though the introduction of 

transcription in the 1980s spurred molecular biology development, 

 transcribed mRNA was unstable, requiring lipid systems to encapsulate the mRNA. The treatment also heightened inflammatory reactions. But Weissman, a new colleague of Karikó, proved to be the perfect partner for her research. As an immunologist, he worked primarily with dendritic cells, which are vital to immune surveillance and activating vaccine-induced immune responses. Together they began to focus on the interaction of different RNA types with the immune system.

Karikó and Weissman’s breakthrough came when they began studying why dendritic cells recognized 

transcribed mRNA as a foreign substance, while mRNA from mammalian cells did not have the same response. They knew that the bases of RNA from mammalian cells are often chemically modified, while in 

 transcribed mRNA is not. Karikó and Weissman produced variants of mRNA with different chemically altered bases and found that when those mRNA were delivered to dendritic cells, the inflammatory reactions were almost completely abolished. This discovery fundamentally altered the understanding of how cells recognized and respond to mRNA.

In 2005, Karikó and Weissman published the results of their research, 15 years before the COVID-19 pandemic began. In later studies published in 2008 and 2010, they proved that mRNA with base modifications shows a significant improvement in protein production compared to unmodified mRNA. Thanks to their findings, the two major roadblocks in mRNA development had been eliminated, and several companies began working to develop the method. And after the COVID-19 outbreak, two base-modified mRNA vaccines were able to be developed at record speed. The Nobel prize honors the work of Karikó and Weissman, and the critical role it played in combatting one of the greatest health crises of the modern age.

The prize was awarded jointly to Katalin Karikó and Drew Weissman for their groundbreaking discovery regarding modification of the bases in mRNA. 

2023 Nobel Prize in Medicine Awarded for Development of mRNA Vaccines Against COVID-19

On Sept. 27, 2023, Gritstone bio, a clinical-stage biotechnology company, announced it has been awarded a contract by the Biomedical Advanced Research and Development Authority (BARDA) for the randomized Phase IIb study of its self-amplifying mRNA (samRNA) vaccine. The samRNA vaccine contains Spike antigen (similar to first-generation COVID-19 vaccines), as well as other viral targets to defend against COVID-19. The contract, valued at up to $433 million, is part of ‘Project NextGen’, a US Department of Health and Human Services (HHS) initiative that aims to push forward new and innovative vaccines and therapeutics providing larger and more long-lasting defenses for COVID-19.

As agreed upon in the contract, Gritstone bio is set to run a 10,000-participant, randomized Phase IIb double-blinded study that will compare its next-generation COVID-19 vaccine candidate against an approved COVID-19 vaccine. The study will test the immunogenicity, safety, and efficacy of the candidate, and it will be run in the United States alongside the COVID-19 Prevention Network (CoVPN). The CoVPN, which is supported by the National Institute of Allergy and Infectious Diseases (NIAID), is a network of clinical trial sites located at Fred Hutchinson Cancer Center with experience conducting large-scale COVID-19 vaccine trials.

This new vaccine candidate is a part of Gritstone bio’s CORAL program. The CORAL program uses self-amplifying mRNA and novel immunogens containing Spike antigen and additional viral targets to enhance B and T cell immunity. As of the publication of this article, the program has conducted three Phase I trials across a variety of patient populations and settings, including vaccine-naïve healthy and HIV+ subjects in South Africa, and healthy volunteers after primary series of approved COVID-19 vaccines. The results of these studies have showed high neutralizing antibody levels for at least six months and wide T cell responses. The CORAL program is supported by BARDA, NIAID, the Coalition for Epidemic Preparedness Innovations, and the Bill & Melinda Gates Foundation.

samRNA is a quickly emerging platform technology that can be used to develop multiple vaccines by changing the sequence of the antigen encoded in the vector RNA and delivered in a lipid nanoparticle. samRNA vaccines, much like traditional mRNA vaccines, use the translation system of the host to change mRNA to protein target antigens, encouraging immunity. But unlike mRNA, samRNA makes multiple copies of the antigen RNA once in the cell, which can lead to longer and amplified antigen expression.

The contract is part of US Department of Health and Human Services’ ‘Project NextGen’ initiative, aimed at pushing forward new and stronger COVID-19 vaccines and therapies.

BARDA Awards Gritstone bio $433 Million Contract for Phase IIb Study of Next-Gen COVID-19 Vaccine

On Sept. 12, 2023, Torx Software Limited announced a collaboration with CDD Vault to allow for the smooth synthesis and registration of new compounds throughout the small-molecule discovery process. Torx is a cloud-based platform created by Cresset and Elixir Software that provides a space for chemistry teams to collaborate, design molecules, and track compound synthesis throughout the design-make-test-analyze (DMTA) cycle. CDD Vault is a hosted data management system for chemical registration and safe storage of scientific data.

Data obtained in Torx can be easily transferred and stored in CDD Vault, which aims for ideal productivity and security. Any of the Torx modules can initiate CDD Vault integration, allowing chemists and managers easy access to data from the CDD vault. These data will hopefully assist throughout the DMTA process, making all steps in the cycle more effective. Gathering registration data in Torx allows chemists to review and approve molecule syntheses prior to automatic deposition in CDD vault via the API integration. As a result, they will be able to work more effectively in a single application while gathering detailed DMTA metrics and data.

In a press release for Torx, Dr Barry Bunin, CEO of CDD Vault, said, "CDD Vault is a whole solution for drug discovery informatics structure activity relationship (SAR) management differentiated via ease-of-adoption and scalable data partitioning capabilities. We believe in the value of collaboration and building an ecosystem of software partners that together can better serve our customers. CDD Vault's integration with Torx, a leading platform for drug design and synthesis, will enable a more efficient drug discovery data workflow."

The collaboration will provide easy access and transfer between data in Torx and CDD Vault, upping the efficiency of the small-molecule discovery process.

Torx Software and CDD Vault to Collaborate on Global Drug Discovery

On Sept. 21, 2023, FDA released a new guidance on how the agency plans to utilize alternative tools to remotely evaluate drug manufacturing facilities identified in a marketing application. The application may be a new drug application, an abbreviated new drug application, a biologics license application, or a supplement to any of these applications. These tools include requesting records from manufacturers, remote interactive assessments of facilities, and receiving information from foreign regulatory partners. During the COVID-19 pandemic, FDA was able to use alternative tools to evaluate facilities; now, it intends to continue to use those tools when appropriate. This guidance is intended to assist FDA in keeping operational flexibility and bolstering faster availability of new, generic, and biosimilar drugs for patients.

The guidance covers the risk-based use of alternative tools, the considerations for alternative tools, and the effects of using alternative tools. Considerations include remote regulatory assessments, inspections conducted by trusted foreign regulatory partners (including information sharing with said partners, and foreign regulatory inspections with FDA remote participants), and preapproval inspections and prelicense inspections with FDA remote subject matter experts.

Alternative tools are used by tFDA to assist the agency in verifying that manufacturers are following regulations and consistently producing high-quality drugs. FDA may use alternative tools to support oversight and evaluation in advance, in lieu, or in support of an inspection. This guidance is not applicable to other drug inspection programs such as post-approval inspections, follow-up and compliance inspections, surveillance inspections, and bioresearch monitoring inspections.

The tools, originally utilized during the COVID-19 pandemic, are now intended to work alongside FDA’s standard procedures.