Susan Haigney

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The European Medicines Agency (EMA) announced on Feb. 23, 2024 that the Committee for Medicinal Products for Human Use (CHMP) has recommended granting market authorization to Qalsody (tofersen). The CHMP opinion will be sent to the European Commission for adoption.

Qalsody is indicated for the treatment of adults with amyotrophic lateral sclerosis (ALS) who have a mutation in the superoxide dismutase 1 (SOD1) gene. It will join the only other treatment for ALS in the European Union, riluzole.

According to EMA, Qalsody, an antisense oligonucleotide that binds to the messenger RNA of the SOD1 gene, reduces the production of SOD1 protein, which leads to an improvement of ALS symptoms. CHMP’s opinion was based on the way the drug works, effects observed in a SOD1 animal model, biomarkers, and clinical data.

The clinical data were obtained from a 28-week, randomized, double-blind, placebo-controlled study. The study included 108 patients from ages 23 to 78 with ALS and a SOD1 gene mutation who were randomly assigned in a 2:1 ratio to receive treatment through a spinal injection with either Qalsody or a placebo. There was an approximately 60% reduction in plasma neurofilament light chain (NfL) concentrations in the group that received Qalsody compared to those who got the placebo, which suggested a reduction in neuronal injury. A numerical improvement was also noted in the physical abilities of the patients who received the drug compared to the placebo.

The marketing authorization applicant for Qalsody has been asked to submit post-authorization data “to further characterize the long-term efficacy and safety of Qalsody, on the basis of an open-label long-term extension study, collaboration with two disease registries, and an observational registry-based study. In addition, it will be investigated if the use of tofersen can delay or even prevent emergence of clinically manifested ALS in presymptomatic SOD1‑ALS patients,” EMA stated in a press release.

ALS patients have a mean survival time of two to five years, according to EMA. ALS causes gradual deterioration of the nerve cells in the brain and spinal cord that control voluntary movement. This deterioration causes a loss of muscle function and paralysis of voluntary muscles, including respiratory failure.

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The agency has recommended granting marketing authorization to ALS treatment, Qalsody (tofersen), for adults who have a mutation in the superoxide dismutase 1 (SOD1) gene.

EMA Recommends New ALS Treatment

On Feb. 15, 2024, FDA’s Center for Drug Evaluation and Research (CDER) released its report, 

. The report describes the center’s key safety programs and activities involved in promoting and protecting public health and dealing with the drug overdose crisis.

FDA performs postmarketing surveillance and risk evaluations on products to identify new adverse events that were not present in the approval process. New information is investigated and may require changes in prescribing information or modification of a Risk Evaluation and Mitigation Strategy (REMS). CDER’s pharmacovigilance efforts in 2023 included reviews of 15 newly identified safety signals (NISS). One of these NISS was related to naloxone hydrochloride product administration. There were attempts to administer a syringe that had no needle. In response, FDA required changes to carton labeling to include a warning that said, “Needle not included.”

Other safety efforts by CDER include medication error prevention. In 2023, the Prevention of Overdoses and Treatment Errors in Children Taskforce Initiative was a collaboration between public health agencies, professional and private sector organizations, health care advocates, and academic experts “to develop strategies to keep children safe from unintentional medication overdoses.”

FDA’s Sentinel Initiative, which is an active surveillance program that evaluates drug safety, saw completion of pilot projects for the integration of signal identification tools into the agency’s routine pharmacovigilance program. In 2023, analyses were conducted that added to the agency’s approval of Paxlovid to treat COVID-19.

“The Sentinel System has transformed the way [a]gency scientists monitor FDA-regulated medical products. Now one of FDA’s leading evidence-generation platforms that can explore and address regulatory questions posed by review teams, Sentinel serves to advance the science of real-world data (RWD) and real-world evidence (RWE),” the report stated. “By making it possible to analyze emerging risks associated with FDA-regulated medical products and to study medical care more broadly, Sentinel enables the [a]gency to assess medical product safety, describe medical product utilization, and characterize medical events under real-world conditions.”

Impurities and contaminants in medications were also addressed in 2023. A new cross-center program was created that was overseen by the Emerging Impurities and Contaminants Committee (EICC). The program brought together experts from different centers within FDA to develop solutions and guidance. Projects and initiatives were created to improve the response to novel or complex impurities. An EICC Charter was established and met on a regular basis to develop programs to address impurities. A 

was published in August 2023 that provided a framework for predicting the mutagenic and carcinogenic potential of nitrosamine drug substance-related impurities.

CDER made efforts in the drug overdose crisis by expanding access to opioid overdose reversal products. The first nonprescription naloxone nasal spray was approved in March 2023, with a generic version approved in July 2023.

“The public health crisis of addiction and overdose continues to persist in our country, with drug overdose deaths reaching more than 106,000 in 2023. As part of our ongoing commitment to address the nation’s overdose crisis, we made changes to the prescribing information of two highly misused drug classes, opioids, and stimulants, to increase safe use and address concerns of nonmedical use, addiction, and overdose,” Patrizia Cavazzoni, director of CDER, said in the report. “We continued to protect the public from impurities and contaminants in medications, including activities to address unexpected impurities; informed the public about product recalls; and worked to improve the overall quality of compounded medications,” she also said in the report.

FDA's Drug Safety Priorities FY23 describes the center’s key safety programs and activities involved in promoting and protecting public health.

FDA’s Drug Safety Priorities for 2023

The European Medicines Agency (EMA) and the Heads of Medicines Agencies (HMA) announced on Feb. 15, 2024 that they have launched two public electronic catalogues for real-word data (RWD). The RWD catalogues will help regulators, researchers, and pharmaceutical companies identify suitable data sources for research and assessment of study protocols and results.

Created to promote transparency, encourage good practices, and build trust in RWD, the catalogues build on former databases developed by the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP). The RWD sources catalogue replaces the ENCePP Resources Database. The RWD studies catalogue replaces the European Union electronic register of post-authorization studies. The ENCePP website has been renewed. Data sources, centers, and networks have migrated to the new catalogues; however, some content will remain on the renewed ENCePP website.

Improvements over the previous databases have been included in the new catalogues. An agreed set of metadata have been used to describe and connect data sources to studies, based on a list of metadata published by the HMA-EMA Big Data Steering group in May 2022. Functionalities have been implemented such as a wider set of metadata, enhanced view, and export and data submissions.

“The publication of the RWD catalogues brings the European medicines regulatory network closer to more data-driven regulation. Improving discoverability of data is one of the priorities set in the HMA-EMA joint Big Data Task Force final report (phase two), reflected in the European medicines agencies network strategy to 2025 and implemented through the joint HMA-EMA Big Data Steering Group workplan. Ultimately, these developments will help European patients receive better medicines faster and promote safe and effective use of the medicines on the market,” EMA stated in a press release.

about the catalogues will be hosted by EMA on March 4, 2024. 

Two public electronic catalogues will be available for real-world data sources and for real-world data studies.

EMA and HMA Launch Real-Word Data Catalogues

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Nelson Labs announced on Feb. 14, 2024 that its facility in Itasca, Ill., is being established as a Pharmaceutical Center of Excellence for parenteral and ophthalmic drug product manufacturers. The facility will feature more than 30,000 square feet of space and include instrumentation for full chemistry, manufacturing, and controls (CMC) support.

The laboratory is compliant with current good manufacturing practices and includes a SKAN isolator suite for performing testing for sterility assurance. The suite will add to the lab’s existing sterility assurance capabilities. The lab will also provide support for drug substances, drug products, raw materials, and primary container closure release and stability studies, including high-performance liquid chromatography (HPLC), ultra-high performance liquid chromatography, ion chromatography, LC-mass spectrometry detector (MSD); spectroscopic, including UV-Vis, Fourier transform infrared spectroscopy, and atomic absorption; spectrometric, including Inductively coupled plasma mass spectrometry.

“The development of a Pharmaceutical Center of Excellence at our Itasca laboratory reflects our commitment to providing comprehensive CMC support services for POPD,” said Aryo Nikopour, vice president, Global Segment Leader, Pharma, Nelson Labs, in a press release. “Nelson Labs has been a global leader in laboratory testing for over 35 years, known for its scientific excellence and commitment to quality. We are excited to enter this next stage of world-class testing for pharmaceutical and biopharmaceutical products.”

Nelson Labs provides microbiological and analytical chemistry testing and advisory services for the medical device and pharmaceutical industries. The company as more than 3000 customers and facilities in the United States, Mexico, Asia, and Europe. Services include more than 900 laboratory tests and regulatory consulting.

The company’s Itasca, Ill., facility will offer chemistry, manufacturing, and controls analytical testing support.

Nelson Labs Creates Center of Excellence for Parenteral and Ophthalmic Drug Manufacturing

The European Medicines Agency (EMA) announced on Feb. 9, 2024 that its Pharmacovigilance Risk Assessment Committee (PRAC) is reminding healthcare professionals that there is a risk of serious adverse events associated with the use of the COVID-19 treatment, Paxlovid (nirmatrelvir, ritonavir), in combination with calcineurin inhibitors and mechanistic target of rapamycin (mTOR) inhibitors, which are immunosuppressants that have a narrow safe dosage range. A drug–drug interaction may reduce the body’s ability to eliminate the medicines, according to EMA.

Calcineurin inhibitors (tacrolimus, ciclosporin) and mTOR inhibitors (everolimus, sirolimus) are used to treat autoimmune disorders or for preventing rejection of transplanted organs. CHMP warns that Paxlovid should only be given with these drugs if blood levels can be closely monitored. “Healthcare professionals need to consult with a multidisciplinary group of specialists to manage the complexity of taking these medicines together,” the agency stated in a press release.

“Paxlovid must not be given in combination with medicines for which elimination from the body is highly reliant on a set of liver enzymes (proteins), known as CYP3A, and that also have a narrow safe dosage range. This includes the immunosuppressant called voclosporin. Before starting the treatment with Paxlovid, healthcare professionals should carefully weigh the potential benefits of Paxlovid treatment against the risks of serious adverse reactions in case of administration together with immunosuppressants,” the agency stated in the release.

This warning comes after PRAC reviewed reports of adverse events that included deaths believed to be the result of drug-–drug interactions between the specific immunosuppressants and Paxlovid. Reports of blood levels rapidly increasing to toxic levels were found.

The agency’s safety committee stressed the risk of potential adverse reactions involved with taking Paxlovid (nirmatrelvir, ritonavir) in combination with certain immunosuppressants.

EMA Issues Reminder Over Paxlovid Risks

The European Medicines Agency (EMA) announced on Feb. 8, 2024 that it has accepted three academic and non-profit organizations into its pilot scheme for advanced therapy medicinal products (ATMPs) development. The pilot’s goal is to guide non-commercial developers of ATMPs through the regulatory and scientific requirements and advance the development of their products to reach the market authorization stage.

The Hospital Clínic de Barcelona was the first participant selected at the start of the pilot. It is developing a medicine to treat patients older than 25 years with relapsed/refractory acute lymphoblastic leukemia. ARI-0001, a chimeric antigen receptor (CAR) product which is based on patients’ own T-cells, was granted Priority Medicine (PRIME) eligibility in December 2021.

In December 2023, EMA selected two new participants from 11 candidates. Berlin Center for Advanced Therapies (BeCAT)–Charité is developing a gene therapy, TregTacRes, based on modified T-cells as an add-on therapy after transplantation.Fondazione Telethon is developing a treatment for Wiskott-Aldrich Syndrome, a rare, life-threatening immunodeficiency.

“Non-profit academic developers are a major contributor to the development of ATMPs, but experience has shown that navigating regulatory requirements can be challenging. While the pilot does not introduce any new regulatory tools, EMA is committed to support participants in leveraging the use of existing regulatory tools and development support measures. The selected pilot participants will benefit from fee reductions and waivers as stated in the Decision of the Agency’s Executive Director on fee incentives for scientific advice, marketing authorization applications, and pre-authorization inspections,” the agency stated in a press release.

The agency expects to add an additional two developers to the pilot by the end of 2024. A report detailing the pilot’s initial results is expected in 2025 and will provide areas for improvement in support for academic developers.

Developers wishing to apply for the pilot scheme can contact the agency at atmppilot@ema.europa.eu or complete a form on the agency’s website.

The three non-commercial developers of ATMPs will benefit from enhanced support from the agency. 