Susan Haigney

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

The European Medicines Agency announced on Oct. 18, 2024 that its Committee for Medicinal Products for Human Use (CHMP) has recommended 10 new medicines for marketing approval, including five new drugs, one orphan drug, two biosimilars, and two generic drugs (1). This brings the total of new medicines receiving positive opinions to 89 in 2024. Extensions for indications were also granted to six drugs.

Two vaccines, Fluad and Flucelax, were approved for immunization against influenza. Fluad is a surface antigen, inactivated, adjuvanted vaccine for use in adults 50 years of age and older. Flucelvax, which is a surface antigen, inactivated and prepared in cell cultures, may be used in adults and children, two years of age and older.

Alhemo (concizumab) for routine prophylaxis of bleeding in patients with haemophilia A or B with inhibitors

Korjuny (catumaxomab) to treat intraperitoneal malignant ascites, “a build-up of fluid containing cancer cells in the abdomen of cancer patients,” according to EMA.

Siiltibcy (rdESAT-6/rCFP-10) to diagnosis 

Wainzua (eplontersen), designated an orphan drug, to treat adults with hereditary transthyretin-mediated amyloidosis

Buprenorphine Neuraxpharm (buprenorphine) to treat opioid addiction.

In addition, two biosimilars, Absimky (ustekinumab) and Imuldosa (ustekinumab), were granted positive opinions for the treatment of plaque psoriasis in children and adults, psoriatic arthritis, Crohn’s disease, and ulcerative colitis. The generic drug, Eltrombopag Viatris (eltrombopag), was also recommended for the treatment of children and adults with primary immune thrombocytopenia and thrombocytopenia associated with chronic hepatitis C.

CHMP also recommended extending indications for Cerdelga (eliglustat), Hepcludex (bulevirtide), Kevzara (sarilumab), Kisqali (ribociclib), Tevimbra (tislelizumab), and Yselty (linzagolix choline). Updates to the COVID-19 vaccines Nuvaxovid and Bimervax were also given positive opinions.

At the meeting, CHMP also stated that it is confirming its recommendation, originally issued in June 2024, to refuse authorization for Masitinib AB Science (masitinib) for the treatment of amyotrophic lateral sclerosis after re-examination of the application.

“At the time of the initial evaluation, the agency considered that the study data were not reliable, as findings from good clinical practice inspections coordinated by EMA and other regulatory authorities had identified issues with the conduct of the study that could not be sufficiently addressed by the company. In addition, the benefits of Masitinib AB Science could not be convincingly demonstrated; the study found no difference between the medicine and placebo in the main measure of effectiveness for the total study population and had several methodological issues. These concerns did not change after re-examination of the data provided and following consultation of a group of experts in neurology, as well as patient representatives. In reaching its final decision, the agency also considered information shared by patient organizations (so-called third-party interventions). Therefore, the Agency maintained its opinion that the benefits of Masitinib AB Science did not outweigh its risks and recommended refusing marketing authorization,” the agency stated on its website (2).

 Two drug applications were withdrawn from consideration. Apremilast Viatris (apremilast), to treat plaque psoriasis, active psoriatic arthritis, and mouth ulcers caused by Behçet’s disease, was withdrawn because the agency found that the data provided did not match bioequivalence conclusions. The epilepsy drug, Epixram (levetiracetam), was withdrawn because of a change in the company’s regulatory strategy.

EMA. Meeting Highlights from the Committee for Medicinal Products for Human Use (CHMP) 14–17 October 2024. Press Release. Oct. 18, 2024.

Articles

The agency’s CHMP recommended drugs to treatments for hemophilia, two biosimilars for psoriasis, and two flu vaccines at their October meeting.

Several Medicines Recommended by EMA’s CHMP in October

The European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) reconfirmed its rejection of the conditional marketing authorization of Translarna (ataluren) after reexamination of the data, the agency announced on Oct. 18, 2024. EMA stated in a press release that the effectiveness of the drug, used to treat Duchenne muscular dystrophy in patients two years of age and older, has not been confirmed (1).

CHMP’s initial negative opinion was issued in September 2023 and confirmed after a previous reexamination in January 2024. The European Commission requested that EMA revisit the opinion in June 2024 to review real-world data and the views of a scientific advisory group. Another reexamination was requested by the sponsor company. CHMP then reviewed results from study 041, patient registry data, and new analysis provided by the company.

According to CHMP, study 041, which looked at the effect of Translarna on a specific subgroup of patients with a progressive decline in the ability to walk, showed “that the distance patients could walk in six minutes after 18 months of treatment decreased by about 82 meters in the Translarna group compared with 90 meters in the placebo (dummy treatment) group; however, this difference was not statistically significant, meaning that it may be due to chance,” the agency stated in the press release. “Similarly, when looking at the decline in motor functions after about 18 months as measured using a standard scale called North Star Ambulatory Assessment (NSAA), the difference between patients treated with Translarna and those who received placebo was also not statistically significant. The CHMP therefore concluded that study 041 had failed to confirm the effectiveness of the medicine.”

Data from two patient registries, STRIDE and CINRG DNHS, were also studied. STRIDE patients were treated with the drug for 5.5 years and patients from CINRG DNHS were not treated with the drug. Results from the registries suggested a delay in the loss of the ability to walk with those treated with the drug; however, CHMP stated that differences between the registries and biases made the comparison inconclusive. Data also did not outweigh the negative results of two post-authorization studies, according to CHMP.The mechanism of action for the drug was also not confirmed, according to the agency.

“Throughout its review of Translarna, the CHMP consulted parents of boys and men with Duchenne muscular dystrophy of different ages. They were invited to meetings as patient experts along with other experts, including neurologists, to describe what it is like to live with this disease, and they spoke directly to the CHMP on several occasions. The patients’ and parents’ perspectives have been sought and captured at every stage of the evaluation of this medicine. The Committee also considered all third-party information received from parents and caregivers of boys affected by Duchenne muscular dystrophy, patient organizations, healthcare professional organizations, and treating doctors.”

“The CHMP acknowledges the high unmet medical need for an effective treatment for patients with Duchenne muscular dystrophy. However, based on all the evidence accumulated, it concluded that the effectiveness of Translarna has not been confirmed in patients with Duchenne muscular dystrophy caused by a nonsense mutation, including those who were expected to have a better response to treatment,” the agency stated in the press release.

EMA. Translarna: EMA Re-confirms Non-renewal of Authorization of Duchenne Muscular Dystrophy Medicine. Press Release. Oct. 18, 2024.

The agency has reconfirmed its recommendation to not give positive opinion to Translarna (ataluren) after a reexamination of the available data.

EMA Denies Authorization of Duchenne Muscular Dystrophy Treatment, Again

Tech Transfer Considerations

® spoke with Ahmed Youssef, senior manager, USP Process Development at Ascend, to get his input on how tech transfer may be complicated when dealing with emerging therapies, such as antibody-drug conjugates, cell and gene therapies, and patient-centric treatments. Youssef pointed to timing as being key for technology transfer.

“It takes an innovator around 12 to 24 months to make a product ready, tech transfer it, [and] complete the safety studies for it,” says Youssef. “But there could be other solutions that could be offered in the background that could make this more efficient, faster, and more attractive to product developers.”

When it comes to sponsors and contract organizations working together to ensure a secure tech transfer, Youssef says the contract development and manufacturing organization (CDMO) should shoulder the responsibility. “A good CDMO [should] have structured communication, because communication is key … when you're talking to your business partner. We always build that in a more collaborative environment,” says Youssef. “[A CDMO needs] to protect the IP rights of their clients, their partners, as well as good documentation practices, in addition to a solid IT department. All of that gives the assurance to the security of the data and the security of the transfer information between the CDMO and their partner.”

Youssef also gave his insights on how sponsors can benefit when contractors offer end-to-end services. “If you mean by end-to-end, the whole process, you know, without the whole offering, from the start of plasmid manufacturing till commercial manufacturing of the batches, and then the fill and finish and release, understand that the advantage would be that you're running all of that under one MSA [master supply agreement], one big MSA,” said Youssef.

Click the video above to watch the interview.

Videos

Ahmed Youssef, senior manager, USP Process Development at Ascend, provides insight on tech transfer when developing and manufacturing emerging therapies and new modalities.

The European Medicines Agency (EMA) and the Heads of Medicines Agency (HMA) announced that the draft joint strategy for the European Union to 2028 (EMANS 2028) is now open for public consultation. The consultation period will be open until Nov. 30, 2024.

 has been reviewed and updated as regulatory and technical situations have changed rapidly (1). New regulations (e.g., legislation to address public health emergencies and reform of the EU medicines regulations) and technical advances, such as the use of artificial intelligence (AI), have spurred the changes to the original strategy.

“Since EMANS 2025, the availability and use of AI have become more commonplace, and the network aims to harness the full potential of AI across all the EMANS focus areas. The use of digital technology and AI has the potential to transform the network’s core work of evaluating human and veterinary medicines for authorization and monitoring their safety through the EU’s pharmacovigilance system. For veterinary medicines, the network will also push ahead with its vision to implement new digital solutions in its European Veterinary Big Data strategy,” the strategy document states (1).

The strategy to 2028 will focus on creating pathways to medicines in the EU. There is also a plan to find ways to leverage data, digitalization, and AI to improve processes.Innovation and competitiveness are priorities that will be nurtured through a regulatory science and research environment, according to EMA. Strengthening the supply chain and the sustainability of the EU network are also on the agenda. Each focus area will be evaluated by EMA and HMA to assess progress and adapt approaches, if necessary.

“The six focus areas have been carefully chosen to support the network’s core work of evaluating medicines as we take strides to promote the development of medicines and ensure that they reach those who need them,” said Maria Lamas, chair of the HMA Management Group, in a press release (2).

“The overarching theme of our updated strategy to 2028 is that of change—rapid, somewhat unpredictable, but nonetheless full of promise,” said Emer Cooke, EMA executive director, in the press release (2). “It will guide the network as it seizes opportunities and meets the challenges of the near future, including preparing for and responding to public health emergencies and threats such as antimicrobial resistance. Now is the time to share your views and help shape the direction of the network for the next few years.”

Stakeholders may provide input through an online questionnaire until Nov. 30, 2024. [https://ec.europa.eu/eusurvey/runner/EMANS2028publicconsultation] The strategy will be finalized after the consultation period and be implemented through multi-annual workplans. The final strategy is expected to be adopted by March 2025.

“While EMANS 2028 cannot preempt the legislative changes or predict the future, this strategy will prepare the network for the revisions to the pharmaceutical legislation and further changes to the technological and regulatory landscape,” Cooke says in the document’s introduction.

Seizing Opportunities in a Changing Medicines Landscape, The European Medicines Agency Network Strategy 2028 (draft)

EMA. Seizing Opportunities in a Changing Medicines Landscape. Press Release. Oct. 9, 2024. 

The draft joint network strategy for the EU until 2028 will be open for public consultation until Nov. 30, 2024.

EMA and HMA Publish Network Strategy for Public Consultation

CPHI Milan 2024: Heparin and Heparinoids in Pharmaceuticals

 sat down with Joan Bassa, Human Health Business Unit Director at Bioiberica, to talk about the history of heparin, its uses in pharmaceuticals, and what heparinoids have to offer the industry.

“Heparin has been [around] for more than 50 years, [and is] the product of [choice] against thrombosis, that, by the way, is still now one of the most frequent causes of death worldwide. There are other important new applications being researched. For example, there are clinical studies in different phases, some very advanced, on the use of heparin, for example, in malaria, as well as in some respiratory diseases like COPD [chronic obstructive pulmonary disease], or for instance, in facilitating the mechanism of childbirth in certain conditions that could affect the viability of the newborn. These probably are the most remarkable in the in the past few years.”

According to Bassa, heparinoids inhibit blood clots and anti-inflammatory properties, especially in patients who cannot use heparin. Heparinoids can be used in wound healing, ulcers, inflammatory diseases, or in vascular diseases. “Heparinoids can be administered orally in topical gels, for example, or ointments, or depending on the quality and the purity, they can also be injected,” says Bassa. “In the case of heparin, all the heparin, basically is injected. So, these are the main differences. But it's true that more and more, heparinoids are becoming an important product to be used in in these different applications.”

"At Bioiberica, we are committed to the highest manufacturing excellence standards," Bassa says. "Through our vertically integrated supply chain, we give peace of mind to our customers, ensuring the highest quality, safety, and full traceability of our products."

Click the above video to watch the full interview.

 is being held from Oct. 8–10, 2024 in Milan, Italy.

Pharmaceutical Technology Europe sat down with Joan Bassa, Human Health Business Unit Director at Bioiberica, to talk about the history of heparin, its uses in pharmaceuticals, and what heparinoids have to offer the industry. 

AAPS PharmSci 360 2024: Predictive Models for Poorly Soluble Drugs

As a preview of what’s to come at this year’s AAPS PharmSci 360, being held Oct. 20–23, 2024 in Salt Lake City, Utah, 

® sat down with Niloufar Salehi, advisor at Eli Lilly & Company, to discuss the problems associated with the formulation of poorly soluble drugs. Salehi also provided a look at how predictive models and other tools can be used to predict and improve solubility in both small-molecule and biologic drugs.

“There are several predictive tools that are used in order to determine poor solubility at [the] early stage of development,” says Salehi in the interview. “One of those is, for example, in silicon modeling that involves using computer simulations to provide insight on how [a] drug will behave in different media, and that can help scientists to identify the potential solubility issues before going any further. Also, another approach is high-throughput screening, which allows [a] researcher to quickly test the solubility of a large number of compounds, and that's enabled the scientists to identify whether there is any modification required for the further development.”

Salehi will be moderating the Symposium: Accelerated Development of Poorly Soluble Drugs Using Predictive Tool at AAPS PharmSci 360 on Tuesday, Oct. 22, 2024. Presentations include the following:

Biorelevant Media and Relevance in Current Time
Speaker: Sandra Klein, University of Greifswald

 Predictive Tools in Early Drug Product Development
Speaker: Fady Ibrahim, Sanofi

Role of Multi-Compartment Systems for Low-Solubility Weak Base Drug
Speaker: Yasuhiro Tsume, University of Michigan

 Predictive Dissolution Data with Pre-Clinical and Clinical Studies
Speaker: Stephen D. Stamatis, Eli Lilly & Company.

Pharmaceutical Technology sat down with Niloufar Salehi, advisor at Eli Lilly & Company, to talk about the session she is moderating at AAPS PharmSci 360 2024, Symposium: An Accelerated Development of Poorly Soluble Drugs Using Predictive Tool.