Daria G. Husni

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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."

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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

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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.

FDA Releases Guidance on Using Remote Oversight Tools for Drug Approval

On Sept. 20, 2023, Alexion, AstraZeneca’s rare disease group, completed the purchase and license agreement for a portfolio of preclinical rare disease gene therapy programs and enabling technologies from Pfizer. The acquisition cost AstraZeneca up to $1 billion, with the addition of tiered royalties on sales.Alexion hopes to create new genetic therapies, improving their safety and efficacy; the portfolio will bolster Alexion and AstraZeneca’s current work on genomic medicine.

Alexion entered into the agreement with Pfizer near the end of July 2023. The profile included sever novel adeno-associated virus (AAV) capsids, which have demonstrated to be effective for delivering therapeutic gene cargos for gene therapy and gene editing. Alexion reported that several Pfizer employees associated with the portfolio will join Alexion’s team as employees.

Alexion was formed as a group within AstraZeneca that focuses on rare diseases, following AstraZeneca’s acquisition of Alexion Pharmaceuticals in 2021. Alexion centers its research on novel molecules, focusing on the complement cascade and its development efforts on hematology, nephrology, neurology, metabolic disorders, cardiology, and ophthalmology.

, Marc Dunoyer, chef executive office at Alexion, said, “Today’s announcement represents another major step forward in Alexion and AstraZeneca’s ambition to be an industry leader in genomic medicine, which has potential to be transformative and even curative for patients with devastating diseases. We look forward to continuing our work to develop enhanced platforms and technologies with broad therapeutic application while integrating best-in-class expertise to accelerate promising therapeutics into the clinic.”

The AstraZeneca rare disease group hopes to use these new gene therapy programs to bolster its work on genomic medicine.

Alexion Completes Purchase and License Agreement of Rare Disease Gene Therapy Portfolio from Pfizer

On Sept. 15, 2023, GSK announced that its myelofibrosis treatment, Ojjaara (momelotinib) had been approved by FDA. The approval covers treatment of intermediate or high-risk myelofibrosis in adults with anemia, regardless of prior therapies. According to GSK, this is the first and only treatment for myelofibrosis patients with anemia. Nearly every myelofibrosis patient will develop anemia, and over 30% discontinue their myelofibrosis treatments due to it. Ojjaara also treats constitutional symptoms and splenomegaly (enlargement of the spleen).

Ojjaara is a once-a-day, oral JAK1/JAK2 and activin A receptor type 1 (ACVR1) inhibitor. It works along three key signaling pathways: Janus kinase (JAK) 1, JAK2, and activin A receptor type 1 (ACVR1). Inhibition of JAK1 and JAK2 can improve constitutional symptoms and splenomegaly, while inhibition of ACVR1 can decrease levels of the protein hepcidin, which contribute to anemia and are elevated in myelofibrosis. GSK held two Phase III, multicenter, randomized, double-blind studies testing the efficacy of Ojjaara in comparison to two other inhibitors used to treat myelofibrosis, danazol and ruxolitinib. Critically, while danazol and ruxolitinib can treat constitutional symptoms and splenomegaly associated with myelofibrosis, neither of them have been able to treat anemia.

Myelofibrosis is a rare blood cancer that can lead to severely low blood counts, which include anemia and thrombocytopenia. GSK stated that around 40% of patients have moderate to severe anemia at the time of diagnosis, and nearly all patients develop anemia while suffering from the disease. Treatment for myelofibrosis patients with anemia often involves blood transfusions, and more than 30% of patients discontinue myelofibrosis treatment because of anemia. Those that depend on transfusions often have a shortened survival rate. GSK hopes that by targeting anemia, it will make a “significant difference in the treatment regimen for these patients who have limited options to address these aspects of the disease.”

Anemia, experienced by most myelofibrosis patients, has caused over 30% of patients to discontinue their treatment.  

FDA Approves Treatment for Myelofibrosis Patients with Anemia

On Sept. 18, 2023, Cellectar Biosciences announced that its treatment for Waldenstrom’s macroglobulinemia, Iopofosine, had been granted Priority Medicine (PRIME) status by the European Medicines Agency (EMA). Iopofosine is the company’s lead small-molecule drug candidate, meant to treat Waldenstrom’s macroglobulinemia (WM) in patients who have completed two or more prior treatment regimens. It is created to give targeted delivery of idodine-131 directly to cancer cells, limiting the exposure to healthy cells. 

Waldenstrom’s macroglobulinemia is a cancer of the lymphatic system, or lymphoma, which is rare and incurable. It occurs in a B-lymphocyte or B-cell, a type of white blood cell that normally grows into a plasma cell to manufacture antibodies that help fight infections. In WM, a hostile change to the B-cell occurs during the late stages of maturing, causing the cell to multiple into a clone of identical cells. These cells are primarily in the bone marrow, but they also inhabit the lymph nodes and other tissues and organs of the lymphatic system. They produce an abundance of antibodies that build up in the body, causing a variety of issues.

Iopofosine previously received Fast Track designation in the United States from FDA for WM patients who have received two or more previous treatment regimens, as well as relapsed/refractory multiple myeloma and relapsed/refractory diffuse large B-cell lymphoma. EMA has previously granted an Orphan Drug Disease Designation for relapsed/refractory multiple myeloma and Waldenstrom’s macroglobulinemia.

Iopofosine provides targeted delivery of idodine-131 directly to cancer cells.

EMA Grants Priority Medicine Status to Cellectar’s Waldenstrom Macroglobulinemia Treatment

In a European Medicines Agency (EMA) press release on September 9, 2023, the agency’s Pharmacovigilance Risk Assessment Committee (PRAC) outlined new measures to avoid fetus exposure to topiramate-containing medicines. Topiramate is known to cause serious birth defects if used during pregnancy, and medicines containing it may increase the risk of neurodevelopmental problems in children. In the European Union, topiramate-containing medicines are used to treat epilepsy and prevent migraines; in some EU countries they are also used with phentermine for weight loss.

As of the publication of this article, PRAC recommends that unless there is no other treatment available, patients using topiramate to treat epilepsy should not use the medication while pregnant. Topiramate must not be used to prevent migraines or manage body weight while pregnant, and patients who are able to become pregnant must use birth control while taking topiramate. PRAC also recommends a pregnancy prevention program to inform those able to become pregnant of the risks associated with topiramate exposure in the womb.

Regardless of indication, topiramate should only be used by patients who can become pregnant when the following conditions are met:

the patient must take a pregnancy test before starting treatment

they must receive counseling on the risks of topiramate treatment during pregnancy

they must complete an annual risk awareness form during treatment.

These recommendations follow PRAC’s review of three recent observational studies, two of which suggest that children exposed to topiramate in the womb have a two- to three-fold higher risk of neurodevelopmental disorders. PRAC consulted with a group of experts, patient representatives, and specialists during the review. Companies marketing topiramate must conduct a drug utilization study, as well as surveys of healthcare professionals and patients, to evaluate the success of the new measures.

The product information for topiramate-containing medicines will be updated, and a visible warning will be added to the packaging of the medicine. Patients and healthcare professionals will also be provided with information on the risks of using the medication during pregnancy, and patients will be given a patient card with each package of the medicine.

A direct healthcare professional communication will be sent to healthcare professionals prescribing, dispensing, or administering the medicine. It will also be published on EMA’s website.

Topiramate can cause serious birth defects if exposed to children in the womb. 