Pharmaceutical Technology Editors

FDA’s Center for Drug Evaluation and Research (CDER) continues to make rare diseases a priority with teams and programs dedicated to speeding up therapeutic development. Both government incentives and scientific advancements have allowed for drug development for rare diseases.

, “A rare disease is any disease that affects less than 200,000 people in the United States. Drug development for the approximately 7000 rare diseases can be complex for many reasons.” There are approximately 30 million people living in the US who have a rare disease. Many of these diseases have little to no available treatments, because of a lack of participants in rare disease clinical trials and limited understanding of the diseases.

The percentage of drugs approved to treat rare or orphan diseases have increased during the past decade. More than half of CDER’s novel drug approvals in 2021 were for orphan diseases.

CDER is continuing to advance drug development for rare diseases by sharing data with the Critical Path Institute and developing the Rare Disease Cures Accelerator-Data and Analytics Platform. The platform provides a database of information on rare diseases, which can aid in standardization and further understanding. CDER is also working to develop publicly available sets of clinical outcome assessments as part of the Standard Core Clinical Outcome Assessment Grant Program. These steps will aid in trial design, endpoint selections, and other important considerations for drug development.

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FDA’s CDER continues to make rare diseases a priority with drug approvals and programming to speed therapeutic development.

FDA Continues to Make Rare Diseases a Priority with Speedy Therapeutic Development

New England Biolabs (NEB) announced the release of its Luna Probe One-Step RT-quantitative polymerase chain reaction (qPCR) Mix with uracil-DNA glycosylase (UDG) in February 2022. The lyophilized master mix is designed to enable sensitive, linear, real-time detection of target RNA sequences in a room temperature-stable format.

The LyoPrime Luna is the first lyophilized product manufactured by Fluorogenics since NEB purchased the company in 2021, according to a Feb. 9, 2022 press release. The product contains murine RNase inhibitor, deoxynucleoside triphosphate, and a passive reference dye. It incorporates thermolabile UDG, which is well-suited to RNA workflows, as well as deoxyuridine triphosphate to reduce carryover contamination risk between reactions.

"The launch of LyoPrime Luna Probe One-Step RT-qPCR Mix will showcase the first of many NEB lyophilized products that we hope will change the market's perception of ambient, stable molecular reagents," said Martin Lee, managing director of Fluorogenics, in the company press release. "Customers everywhere will benefit from state-of-the-art real-time PCR performance in a more flexible format that additionally reduces the environmental impact of cold shipment and storage."

When measured in NEB’s “dot in boxes” scoring method—a high-throughput data visualization tool that provides quality scores for qPCR outcomes—the LyoPrime Luna outperformed many competitor products and strongly matched the company’s liquid mix, according to the press release.

"The current worldwide focus on infectious diseases has highlighted the need for increased access to robust RNA reagents in a variety of formats,” said Nicole Nichols, associate director of applications and product development, NEB, in the press release. “By lyophilizing our Luna WarmStart RT-based product, we've achieved a one-step RT-qPCR mix that provides the same high level of performance delivered by our liquid master mix. As a standard catalog offering, this will lower barriers to a high-quality lyophilized reagent and simplify the RT-qPCR assay development process.”

The Luna Probe One-Step RT-qPCR Mix with UDG is designed to enable sensitive, linear, real-time detection of target RNA sequences.

New England Biolabs Releases Lyophilized Master Mix

Element Biosciences, a biotechnology company, announced on March 1, 2022 that it has entered into an agreement with Genoox, a community-driven genomic data platform, to validate the clinical potential of its AVITI system. AVITI is Element’s new DNA sequencing platform that is designed to perform whole-genome sequencing in research concerning rare and undiagnosed diseases.

According to a company press release, while the use of sequencing data in clinical research has grown at a “staggering rate”, the density of data in genome-wide approaches has resulted in an interpretation bottleneck. The bottleneck can be circumnavigated by tools such as those developed by Genoox, as these tools can rapidly identify small sets of variants most likely to cause the phenotype of the patients.

An initial study using the AVITI platform sequenced the data of ten individuals with a rare eye disease. In five of these cases, high confidence candidate variants were identified by Genoox’s interpretation platform Franklin. Should these results be clinically validated, the anticipated diagnostic yield of the study will be 50%.

“We are pleased to partner with Genoox,” said Molly He, CEO and co-founder of Element, in the press release. “Our initial study demonstrated how effectively the joint offering works for whole genome sequencing and variant interpretation.”

“The accuracy of the sequencing data that is being produced by Element Biosciences and its AVITI system has the power to unlock the value of whole-genome sequencing and create lasting impacts for the genomics industry,” said Amir Trabelsi, CEO and co-founder of Genoox, in the press release. “Combining the technologies of Element and Genoox enables actionable insights to be drawn from that data.”

Genoox will use their genomic data platform to validate Element's AVITI system.

Element Biosciences Partners with Genoox on Validation Project

An EMA report, published on March 3, 2022, has analyzed the positive impact of the first five years of the Europe Medicines Agency’s (EMA’s) PRIority Medicines (PRIME) scheme. The PRIME scheme allows for the authorization of new medicines that are potentially life-changing for patients with unmet medical needs. Patients with little to no current treatment options were able to access new and emerging treatments at a faster rate, potentially improving their overall health.

EMA stated in a press release that the review of the PRIME scheme showed that, “From March 2016 to June 2021, a total of 18 medicines that had PRIME support were approved in the European Union (EU). Among these, 10 received a conditional marketing authorization (CMA) enabling them to access the market earlier and reach patients more quickly; seven are advanced therapy medicinal products (ATMPs), which have the potential to reshape the treatment of a wide range of conditions; and 16 concern rare diseases.”

PRIME medicines have allowed for faster patient access to innovative treatments for various unmet medical conditions, such as rare cancers and orphan diseases. Innovative technologies such as CAR T-cell therapies, one-time curative gene therapies, and new vaccines were also released faster as a result of the scheme. A total of 98 medicines have been accepted into the scheme as of the time of publication of the report.

EMA’s PRIME scheme has enabled life-changing medicines to become available to patients at a faster rate.

EMA’s PRIME Enables Earlier Availability of Life-Changing Medicines

Mundipharma and Cidara Therapeutics announced on March 3, 2022 that the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) has granted Promising Innovative Medicine (PIM) designation to rezafungin for treatment of invasive candidiasis.

A PIM designation is a prerequisite for the UK’s Early Access to Medicines Scheme (EAMS), which permits the use of medicines not yet approved by the relevant regulatory authorities. A condition must be life-threatening or seriously debilitating, with little to no treatment method or prevention, in order to be granted a PIM designation.

Invasive candidiasis is a life-threatening systemic 

infection of the bloodstream or deep tissues. There is a significant unmet need for successful treatment options for invasive candidiasis; the mortality rate for patients with the infection is as high as 40%.

Rezafungin is being developed for both the prevention and treatment of invasive candidiasis and other serious fungal infections. Cidara Therapeutics is conducting clinical trials of the treatment and is partnering with Mundipharma, which has commercial rights to rezafungin outside the United States and Japan.

“Despite currently available treatments, the mortality rate for patients with invasive candidiasis remains high, demonstrating that there is still a clear unmet need for new treatment options to address this serious disease,” commented Brian Sheehan, PhD, chief scientific officer of Mundipharma, in a press release. “Rezafungin, as a next-generation echinocandin, has the potential to help critically ill, vulnerable patients battling invasive Candida infections. We would like to thank the MHRA for this recognition and look forward to working closely with them to ensure that patients in the UK can benefit from rezafungin.”

MHRA has awarded Promising Innovation Medicine (PIM) designation to rezafungin for the treatment of invasive candidiasis.

MHRA Awards Promising Innovation Medicine Designation for the Treatment of Invasive Candidiasis

Evonik, a specialty chemical company based in Essen, Germany, has increased its supply of plant-derived cholesterol, a crucial component for the manufacturing of messenger RNA (mRNA) vaccines and gene therapies. The production of the cholesterol will meet the increased market demand as it is used in COVID-19 vaccines.

Plant-derived cholesterol is an essential excipient for the lipid-based delivery of large molecules such as mRNA as well as other gene therapies, such as cancer immunotherapy, according to the company. The benefit of using plant-derived cholesterol is the minimized risk of undesired immunological responses and inconsistent quality, which are possible risks when using animal-derived cholesterol.

Evonik’s increased manufacturing capacities for the cholesterol will support the growth of its portfolio of system solutions for advanced drug delivery.

“As one of the few suppliers of high-quality, non-animal-derived cholesterol for the pharmaceutical industry, we are proud to provide innovators with a critical excipient for a wide range of innovative nucleic acid therapeutics,” said Dr. Thomas Riermeier, head of Evonik’s Health Care business line, in a press release. “Increasing our supply of PhytoChol is a timely step to further fuel the development of mRNA and gene therapies as well as biopharmaceutical cell culture applications.”

Evonik has increased its global supply of plant-derived cholesterol used for mRNA vaccines and gene therapies.