EMA’s 2023 new medicines report suggests return to pre-pandemic volume

Quick background: EMA annual new medicines reports

• At the beginning of each calendar year, the EMA publishes a New Medicines Highlights report, providing a high-level overview of new medicines reviewed by the EMA’s Committee for Medicinal Products of Human Use (CHMP). The figures provided in this report only reflect the recommendations made by the EMA and do not reflect any action taken by the European Commission.
• Several months after publishing the Highlights report, the EMA also publishes a detailed annual report. For example, in 2023, the EMA published its 2022 highlights report on February 16, followed by the detailed report on May 15.

The 2023 report is out, and the numbers suggest a possible return to pre-pandemic volumes

• In 2023, the EMA issued a positive opinion for 77 products, of which 39 contained a new active substance, according to the 2023 report. Seventeen products were orphan drugs, fourteen were generics and eight were biosimilars. Eight products received recommendations for conditional marketing authorization and one product was reviewed “under exceptional circumstances.” Only one product was an advanced therapy medicinal product (ATMP), three products held PRIME designation, and three products were evaluated under accelerated assessments. An important note: these numbers are not mutually exclusive. For example, one product (Casgevy; Vertex) was an ATMP, held PRIME designation, qualified as an orphan drug and contained a new active substance, contributing to the total numbers in all of these categories.
• The number of opinions issued by the EMA in 2023 fell in comparison to the previous two years. This most recent year saw 80 total opinions, compared to 92 in 2022 and 97 in 2021. When compared to the year immediately prior to the pandemic, however, 2023 actually marks an increase in volume, with only 70 opinions issued in 2019. The rate of negative opinions over the last three years has remained relatively stable, with three each in 2023 and 2022 and five in 2021.
• The EMA has now seen a three-year decline in new active substances, with 54 in 2021, 44 in 2022 and 39 in 2023. However, this is actually relatively aligned with the number of new active substances seen prior to and during the first year of the pandemic: 39 in 2020; 30 in 2019; 42 in 2018 and 35 in 2017.
• Reviews of orphan medicines and biosimilars have remained stable over the past three years. 2023 saw the review of 17 orphan medicines, compared to an annual average of 20.6 for the years 2020 to 2022. There were eight biosimilars reviewed in 2023, which is comparable to 2021 (seven) and 2022 (eight), but lower than 2020, which saw 12 biosimilars reviewed.
• Conditional approvals and accelerated assessments seem to fluctuate each year, with no clear trend. Conditional marketing authorization is reserved for medicines “where the benefit of immediate availability of the medicine outweighs the risk inherent in the fact that additional data are still required.” In 2023, eight products received a recommendation for conditional marketing authorization, compared to nine in 2022 and 13 in both 2020 and 2021. Accelerated assessment, which can be used for therapeutic innovative products with a broad public health interest, reduces the review time from 210 days to 150 days. Accelerated assessments accounted for six opinions in 2020, three in 2021, five in 2022, and three in 2023. Both of these pathways appear to be impacted at least in part by public health emergencies: in 2020, two products marked for conditional approval were intended for Covid-19 and two products recommended under accelerated assessments were Ebola virus vaccines; in 2021, four products recommended for conditional authorization were intended for Covid-19.
• Although the number of products holding the PRIME (priority medicines) designation declined, this is likely due to product development timelines. The EMA implemented the PRIME scheme to facilitate the development of highly innovative therapeutics that address an unmet medical need. The number of opinions on products in the PRIME scheme dropped to three in 2023, compared to eight in 2020, six in 2021 and eight in 2022. However, as of December 20, 2023, there were 76 products actively in development that had been granted eligibility to PRIME, with three products added in December. This suggests that although only three PRIME-designated products sought approval in 2023, the PRIME scheme continues to be actively utilized by developers. Similarly, only one product in 2023 was recommended for approval under “ exceptional circumstances” – Loargys. This approval type has always been uncommon – before the pandemic, this pathway was used just eight times between 2015 and 2019. [ See AgencyIQ’s analysis of this approval type from 2015-2021 here.]

Four drugs that were recommended for approval in the E.U. did not receive an approval from the U.S. FDA

• Loargys (pegzilarginase; Immedica Pharma), approved in the E.U. in 2023, received a refusal to file (RTF) letter from the FDA in 2022. “FDA requested additional data to support effectiveness, such as evidence showing that plasma arginine and metabolite reduction predicts a clinical benefit in patients.” Additionally, the agency requested further information regarding chemistry, manufacturing and controls (CMC). At the time, the product was being developed by Aeglea; however, the global rights to the product were acquired by Immedica in July 2023. Based on the E.U. approval and discussion with the FDA, the company announced in December 2023 that it intends to re-submit the biologics license application in the U.S.
• Ebglyss (lebrikizumab; Almirall) received a Complete Response Letter (CRL) from the U.S. FDA in October 2023. The product was approved in the E.U. for the treatment of moderate to severe atopic dermatitis in patients 16 years or older on November 17, 2023. The FDA CRL cited inspection findings that arose from a “multi-sponsor inspection of a third-party, contract manufacturing organization” which involved the monoclonal antibody drug substance for lebrikizumab. The clinical package, safety and label were not affected. According to comments from Eli Lilly – which holds the U.S. rights to the drug product – the company plans to work with the FDA and manufacturer to address the identified concerns.
• Yorvipath (palopegteriparatide; Ascendis Pharma) – referred to as TransCon PTH in the U.S. – received a CRL from the FDA in May 2023 due to manufacturing control issues. This hormone replacement medicine, which comes in pre-filled pens for injection under the skin, was approved in the E.U. on November 17, 2023 for treatment of adults with chronic hypoparathyroidism. The FDA CRL raised concerns on the “manufacturing control strategy for variability of delivered dose in the TransCon PTH drug/device combination.” The application was resubmitted to the FDA in December 2023 with a Prescription Drug User Fee Act (PDUFA) goal date of May 14, 2024.
• Lyfnua (gefapixant; Merck) received a CRL from the FDA in 2022 followed by a second CRL in December 2023. Gefapixant is a non-narcotic oral selective P2X3 receptor antagonist for the treatment of refractory chronic cough or unexplained chronic cough in adults. The product received E.U. approval on September 15, 2023 for the treatment of chronic cough that is unexplained or for which other treatments have not worked. In the FDA’s first CRL, the agency requested “additional information related to the measurement of efficacy.” The agency then held a Pulmonary-Allergic Drugs Advisory Committee meeting to discuss gefapixant, which yielded a 12-to-1 vote that “the evidence does not demonstrate that gefapixant provides a clinically meaningful benefit.” Finally, the sponsor received a second CRL from the FDA in December 2023 stating that the “application did not meet substantial evidence of effectiveness.” The EMA notes that although the effects of Lyfnua are modest with respect to reducing daily cough number, the benefits still outweigh the risks.

Other discrepancies between approvals from the EMA and FDA seem to be related to sponsor strategy

• Tevimbra (tislelizumab; BeiGene) is currently pending U.S. FDA review as a first-line treatment; its recent E.U. approval is for second-line treatment. On September 15, 2023, the E.U. approved Tevimbra for the treatment of adults “with unresectable, locally advanced or metastatic esophageal squamous cell carcinoma after prior platinum-based chemotherapy.” The E.U. approval was supported by the RATIONAL 302 study, which was a randomized, active comparator, open-label trial in the second-line setting. However, BeiGene announced that it is seeking approval in the U.S. on the basis of the data from the RATIONAL 306 study, which was a randomized, placebo-controlled, double-blind trial in the first-line setting. According to the sponsor, the PDUFA goal date for this application falls in the second half of 2024.
• Two medicines approved by the EMA in 2023 received FDA approval more than a year earlier, but only as a result of application dates. Inaqovi (cedazuridine/decitabine; Otsuka Pharmaceuticals) is approved in the E.U. for the treatment of acute myeloid leukemia. The U.S. approval (as Inqovi) came in 2020 and carries a broader indication for myelodysplastic syndromes. The EMA received the application for this product on July 26, 2022, and the product was approved in the E.U. on September 15, 2023. Pyclari (piflufolastat [18]; Curium Pet France) is a diagnostic medicine to detect prostate cancer cells containing prostate-specific membrane antigen. The product was approved in the E.U. on November 27, 2023 with an application received by the EMA on June 24, 2022. U.S. approval occurred in 2021, suggesting that any lag in approval between jurisdictions is related to the differing application dates.

Analysis

• The number of EMA recommendations on new medicines in 2023 seems to be back to pre-pandemic levels. The pandemic saw a lot of product development that required rapid review and turnaround to address the public health emergency. And although it seems that fewer products were considered under the PRIME scheme, accelerated assessment or conditional approval in 2023, the fluctuation in these numbers is likely to be due more to public health needs and the inherent variability in product development cycles than any administrative or agency-level reasons.
• Reports on multiple post-pandemic years will be needed to determine whether the numbers reported for 2023 represent a trend or an outlier. The drop in total opinions and changes in the types of products assessed in 2023 may simply be dependent on the applications submitted to the EMA. A few years’ worth of post-pandemic data will be needed to determine any true emerging trends related to the EMA’s recommendations.

To contact the author of this item, please email Kirsten Messmer ( kmessmer@agencyiq.com).
To contact the editor of this item, please email Chelsey McIntyre ( cmcintyre@agencyiq.com).

Key Documents and Dates

• Press release – Human medicines: highlights of 2023, published January 16, 2024
• Report – Human Medicines Highlights 2023, published January 16, 2024