2024 New Drug Approvals: Key FDA and EMA approvals, breakthroughs and market trends

Approval rates for innovative medicines in the EU have bounced back this year after a rather subdued performance in 2023. The US, on the other hand, is struggling to keep pace with last year’s registration bonanza. Let’s take a look at what the pace and emphasis of 2024’s new drug approvals in these key markets tell us about the industry’s current state of health.

In general, 2023 was a year of recovery for drug approvals in both markets especially in the US, where approvals seem to have levelled off to a more established pattern in 2024. In the EU, though, by late November 2024, approval recommendations by the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) had already outstripped positive opinions for the whole of 2023, with one more CHMP meeting scheduled before the end of the year.

US drug market trends 2024

As of late November 2024, the US Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) had approved 40 new molecular entities and new therapeutic biologicals, compared with 55 approvals in 2023. Meanwhile, the FDA’s Center for Biologics Evaluation and Research (CBER) had cleared 15 biological license applications (including source plasma), measured against 25 in the whole of 2023. Current-year CBER approvals take the FDA’s year-to-date tally to 55 products, well behind the combined (and exceptional) CDER/CBER count of 80 approvals for 2023.

EMA positive opinions 2024

As of late November 2024, the CHMP had recommended 55 new medicines or vaccines for approval. The EMA’s positive opinions in 2024 had already superseded the 50 new medicines recommended for approval by CHMP in 2023. This compared with 53 CHMP positive opinions in 2022, which was down from an unusually high 66 positive opinions in 2021.

In most cases, the European Commission follows the CHMP’s approval recommendations, although there may be several months’ delay before the Commission signs off on them. According to publicly available information, 42 of the 52 products recommended by the CHMP had secured European Commission drug approvals at the time of writing.

Continuing approval challenges

Both the US and the EU continue to face challenges that may influence the nature and timing of new drug approvals. In the US, for example, regulatory requirements have recently tightened for accelerated approvals. This followed new provisions included in the Food and Drug Omnibus Reform Act of 2022, which gave the FDA new authority to improve transparency around accelerated approvals and ensure that applicants complied with post-marketing requirements.

Also of note was the introduction of direct price negotiations for high-priced medicines covered by the US Medicare Part D programme from autumn 2023. This was a significant disruption of the established US market model, based on free pricing at source and negotiations with insurers or pharmacy benefit managers. Both developments could theoretically make companies think twice about seeking US approval for new medicines.

In Europe, a radical overhaul of EU pharmaceutical legislation remains in play. The proposals put forward by the European Commission, and subsequently amended by the European Parliament, have raised questions about market access and the sustainability of industry’s business model across the region.

Pending a European Council position on the proposed pharmaceutical regulation and directive (expected in 2026), Parliament has generally diluted the provisions of most concern to industry. These included plans to reduce baseline regulatory data protection (RDP) for newly approved medicines from eight to six years (now 7.5 years in Parliament’s revised version).

Parliament has also removed a controversial requirement for companies to supply new drugs continuously in all EU Member States within two years of approval, if they wanted to claw back two years of lost RDP. There is now an obligation to file nationally for pricing and reimbursement of new medicines, but only in Member States that request submissions, and without linking the obligation to any RDP or market-exclusivity incentives.  

The Commission’s revisions also included proposals to reduce the time taken to evaluate new medicines centrally in the EU. The EMA would have to assess products within 180 days (150 days for medicines of ‘major public health interest’), down from 210 days currently. The Commission would then have 46 rather than 67 days to give its seal of approval. These adjustments remain unchanged following Parliament’s review of the proposed Directive.

Another provision retained in Parliament’s plenary vote on the pharmaceutical legislation was the concept of regulatory sandboxes, with adaptive frameworks including real-world data collection, to expedite approvals of novel therapies. Moreover, Parliament also left in place proposals to expand the application of ‘rolling review’ procedures previously employed for COVID-19 vaccines.

Enhancing review efficiency

A range of factors can shape primary data on drug approvals, including agency resources, the volume, rate and complexity of approval submissions, and spillovers from one year to the next. Meanwhile, the EMA and the FDA continue to be held to account for annual fluctuations. The EMA, for example, recently announced measures, together with the European medicines regulatory network, to enhance the efficiency of its assessment and approval processes for new medicines through:

• Better management of the network’s expert resources;
• Streamlining assessment procedures; and
• Encouragement for better and more comprehensive application dossiers at the time of initial submission.                        

The reliability of long-term planning for initial marketing authorisation applications (MAAs) has been a recurrent problem for the regulatory network, slowing down drug approval times. A recent EMA report found that:

• In 2023, only 35% of MAAs were submitted to the agency on time (in accordance with the date shown on the applicant’s letter of intent).
• Forty-two per cent of companies seeking marketing authorisation asked for more time (or ‘extended clock stops’) to respond to questions from the EMA’s scientific committees, as their data were not sufficiently mature when filed.
• The average duration of clock stops for initial MAAs in 2023 (198 days) was comparable to the average time for assessment (204 days).

Conversely, a January 2024 analysis by regulatory intelligence experts AgencyIQ of CDER approvals in 2023 suggested that regulators themselves were lagging. This was specifically with respect to meeting Prescription Drug User Fee Act (PDUFA) deadlines for completing reviews of licence applications.

Although CDER approved 55 new molecular entities (NMEs) in 2023, 20 more than in the previous year, only 89% of those decisions met their agreed PDUFA target dates. An analysis of the past 10 years showed that CDER had not previously fallen below a 95% annual rate for meeting PDUFA NME target dates. This included rates of 98% and 95%, respectively, in 2021 and 2022, when the FDA faced challenges from the COVID-19 pandemic.

Breakthrough therapies 2024

Approval rates aside, the roster of new molecular entities in 2024 continues to fly the flag for breakthrough innovation.

• In February 2024, the FDA approved Iovance Biotherapeutics’ tumour-derived autologous T-cell immunotherapy Amtagvi (lifileucel) for unresectable or metastatic melanoma. It was the first cellular therapy to be approved for a solid tumour in the US.
• In March 2024, the FDA cleared Orchard Therapeutics’ Lenmeldy (atidarsagene autotemcel), the first available gene therapy for children with early-onset metachromatic leukodystrophy. The therapy was approved by the European Commission branded as Libmeldy in December 2022.                                                   
• In August 2024, the FDA approved Adaptimmune Therapeutics’ autologous T-cell therapy Tecelra (afamitresgene autoleucel), for adults with unresectable or metastatic synovial sarcoma expressing the MAGE-A4 antigen. Tecelra was the first engineered cell therapy for a solid tumour to be registered in the US.                                                 
• The CHMP recommended approval in June 2024 for Merck Sharp & Dohme’s Winrevair (sotatercept), the first activin signalling inhibitor therapy for pulmonary arterial hypertension in adults. The European Commission signed off Winrevair in August 2024, after the FDA approved the drug in March 2024.
• In May 2024, the CHMP issued a positive opinion on Pfizer’s gene therapy Durveqtix (fidanacogene elaparvovec), for haemophilia B in adults without factor IX inhibitors and with detectable antibodies to variant adeno-associated virus serotype Rh74. The European Commission confirmed the conditional approval in July 2024, while the FDA cleared Pfizer’s gene therapy as Beqvez in April 2024.

Shift to specialty products persists

Many of the breakthrough medicines listed above are indicated for rare diseases, building on the dominant trend in recent years of specialty drug approvals, particularly new medicines for rare diseases. Of the 40 new medicines approved by CDER in 2024 to date, 20 have been for orphan-designated medicines. Out of 15 BLAs cleared by CBER, five were orphan-designated. By contrast, a total of 80 new medicines and biologicals were approved in 2023 by CDER and CBER combined, of which 41 were orphan drugs.

In the European Union, the CHMP’s 55 approval recommendations in 2024 to date included 17 orphan-designated products. In 2023, the CHMP’s 50 approval recommendations included 24 orphan drugs.

Some emerging trends in drug development and approvals, such as breakthrough therapies for Alzheimer’s disease and obesity, may suggest that the pendulum is partly swinging back towards high-impact new medicines aimed at large patient populations. This shift could gain momentum from regulatory developments such as:

• Mandatory negotiations on maximum fair prices (MFPs) for high-cost drugs used in the US Medicare system;
• Rebate penalties for above-inflation price increases on Medicare drugs; and
• Potentially restrictive criteria for unmet- or high unmet-medical need qualifying EU-approved new drugs for additional RDP or orphan-market exclusivity.

For example, rebates on above-inflation price increases in Medicare could tip the balance towards volume-driven strategies. In terms of the drug price negotiations impact, the limited grace periods available before MFPs take effect might dampen enthusiasm for current pipeline-in-a-product strategies, geared to cumulative indication-stacking and progressively larger patient populations.

In the EU’s pharmaceutical review, the Commission wanted to replace the current standard 10-year market exclusivity for orphan drugs with a modulated exclusivity. This would have meant nine years’ baseline exclusivity and only five years for drugs approved using bibliographic data. An additional year’s exclusivity would be available for addressing a high unmet medical need, launching an orphan drug in all Member States within two years of approval, or developing new therapeutic indications for an already authorised therapy.

Adopting its position on the European Commission’s proposed pharmaceutical regulation and directive in April 2024, the European Parliament retained the nine-year baseline exclusivity for orphan products. It also strengthened provisions enabling similar medicinal products to orphan drugs (generics and biosimilars) to be filed for approval, and even approved, within two years of the originator’s market exclusivity running out.

The extra year’s exclusivity for timely launches of orphan drugs across the EU was removed, along with two-year launch incentives for new medicines in general. While orphan medicinal products based on bibliographic data would get only four years’ exclusivity under the Parliament’s revisions, those addressing high unmet medical needs (HUMNs) would be eligible for 11 years. The exact scope of the HUMN definition, which industry has some concerns about, remains to be seen.

Parliament also maintained the Commission’s proposal for a global marketing authorisation, eliminating separate periods of exclusivity for different orphan designations of the same product. However, a new therapeutic indication for a different rare disease would be eligible for one extra year’s exclusivity. This extension would be applicable twice, providing each indication were for a different orphan condition, and the approval were granted at least two years before the end of the original exclusivity period.  

Blockbuster innovative drug launches in 2024 and beyond

For all the challenges of regulatory changes in drug approvals, pharmaceutical launch success still comes down to revenues and profit margins. Clarivate’s annual Drugs to Watch report for 2024 singles out 13 products either already launched or scheduled to launch during 2024, and tipped to achieve blockbuster status (annual sales of $1 billion or more) and/or to transform treatment paradigms within five years.

This compares with 15 potential blockbusters included in Clarivate’s Drugs to Watch report for 2023. Some of the latest year’s crop are user-friendly versions of existing drugs, rather than innovative medicines in the NME sense – a reminder that incremental innovation remains pivotal to the industry’s business model. Eli Lilly’s Omvoh (mirikizumab) was included in Drugs to Watch 2023, but its US launch was delayed due to manufacturing concerns.

Five-year sales forecasts were not provided for Omvoh, bluebird bio’s Lyfgenia (lovotibeglogene autotemcel) or for two respiratory syncytial virus (RSV) vaccines, Pfizer’s Abrysvo (RSVPreF) and GSK’s Arexvy (RSVPreF3). However, the potential market for RSV vaccines and prophylaxis over the next five years was estimated at $10 billion.

From R&D to launch excellence

As these blockbuster candidates either prepare to enter the major markets or navigate through the first crucial years of launch impact, companies continue to replenish their drug development pipelines. Citeline Clinical’s Pharma R&D Annual Review 2024 lists 22,825 pipeline prospects as being in active development as of January 2024, 7.20% more than in the previous year’s analysis when pipeline growth year on year was 5.89% (+8.22% in 2022).

Even with long-desired drug approvals in place, companies have to straddle the widening gulf between regulatory approval and market access. New drugs must not only tick regulatory boxes but transition as seamlessly as possible into launch success robust enough to withstand a complex and diverse global marketplace.

With the right launch and market access management tools, such as SmartLaunch® and SmartAccess™, companies can track milestones, timelines, opportunities and challenges, and access plans in real time across different countries, functional silos and management layers. Only when these plans and their outputs are fully visible, aligned and actionable across the organisation can a company ensure that drug approvals really are a seedbed for launch excellence.