Introduction
The European Medicines Agency (EMA), the Food and Drug Administration (FDA) and the Medicines and Healthcare Products Regulatory Agency (MHRA) approved 53 novel medicines in 2024; with 53% of these products being first in class.1
A review by Topouzis et al., 2025 proposed that although less medicines were approved overall by the European, US and UK regulatory agencies in 2024 (53) compared to 2023 (70), the number of orphan drug authorisations was similar and there was a sustained trend in the development of novel therapeutic proteins and advanced therapy medicinal products (ATMPs). The main characteristic of the 2024 approved medicines was their innovative pharmacological designs, enabling these products to effectively address conditions with unmet medical needs. 1
Topouzis et al highlighted the following first-in-class innovative medicines of interest: 1
- Bizengri (Zenocutuzumab)
- Cobenfy (Xanomeline and trospium chloride)
- Ziihera (Zanidatamab)
- Hympavzi (Marstacimab)
- Rytelo (Imetelstat)
Regional approval status of each novel medicine
United States
All products approved
European Union
- Bizengri (Zenocutuzumab): not approved
- Cobenfy (Xanomeline and trospium chloride): not approved
- Ziihera (Zanidatamab): Approved June 2025
- Hympavzi (Marstacimab): Approved November 2024
- Rytelo (Imetelstat): Approved March 2025
United Kingdom
- Hympavzi (Marstacimab): approved April 2025
Zenocutuzumab
Zenocutuzumab was approved for the treatment of advanced, unresectable, or metastatic non-small cell lung cancer (NSCLC) harbouring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy, or advanced, unresectable, or metastatic pancreatic adenocarcinoma harbouring a NRG1 gene fusion with disease progression on or after prior systemic therapy. Zenocutuzumab is a bi-specific humanised antibody designed with an innovative ‘dock and block’ mechanism of inhibition; it targets both HER2 and HER3 proteins and inhibits NRG1 binding. 1
Efficacy was evaluated in the eNRGy study (NCT02912949), a multicenter, open-label, multicohort trial. The trial included 64 adults with advanced or metastatic NRG1 fusion-positive NSCLC and 30 adults with advanced or metastatic NRG1 fusion-positive pancreatic adenocarcinoma who had disease progression following standard of care treatment. NRG1 gene fusion status was prospectively determined by next generation sequencing assays. 2-3
The major efficacy outcome measures were confirmed overall response rate (ORR) and duration of response (DOR). For NSCLC, ORR was 33% (95% CI: 22%, 46%) and median DOR was 7.4 months (95% CI: 4.0, 16.6). For pancreatic adenocarcinoma, ORR was 40% (95% CI: 23%, 59%) and the DOR range was 3.7 to 16.6 months. 2-3
Xanomeline and Tropsium
Xanomeline-tropsium combination, is the first medicine approved to treat schizophrenia that targets cholinergic receptors instead of dopamine receptors. 1
The effectiveness of this drug combination was determined in two identical studies (EMERGENT-2; NCT04659161 and EMERGENT-3; NCT04738123). Both studies were 5-week, randomised, double-blind, placebo-controlled, multi-center studies in adults with a diagnosis of schizophrenia according to DSM-5 criteria. 4-5
The primary efficacy measure was the change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at week 5. Each item in the PANNS 30-item scale was rated by a clinician on a seven-point scale. In both studies, the participants who received xanomeline-tropsium experienced a statistically significant reduction in both negative and positive schizophrenia symptoms (PANSS total score) from baseline to Week 5 compared to the placebo group. 4-5
Zanidatamab
Zanidatamab, a bispecific HER2-directed antibody, for previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), was approved by the FDA under the accelerated approval pathway. It is the first biparatopic antibody that binds to two distinct epitopes of the same molecule. 1
Efficacy was evaluated in HERIZON-BTC-01 (NCT04466891), an open-label multicenter, single-arm trial in 62 patients with unresectable or metastatic HER2-positive (IHC3+) BTC. Patients were required to have received at least one prior gemcitabine-containing regimen in the advanced disease setting. 6-7
The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR). ORR was 52% (95% CI: 39, 65) and median DOR was 14.9 months (95% CI: 7.4, not estimable). 6-7
Marstacimab
Marstacimab was approved to prevent bleeding episodes in patients with Haemophilia A and B (inherited bleeding disorders caused by dysfunction or deficiency of factor VIII and IX, respectively). It is the first haemophilia therapy that restores Factor Xa activity by inhibiting Tissue Factor Pathway Inhibitor (TFPI), as opposed to relying on external supplementation of clotting factors.1
Efficacy was evaluated in BASIS (NCT03938792), an open-label, multicenter, two-phase (6-month observation phase with factor replacement treatment either on demand or prophylactically followed by 12 months of treatment with marstacimab) study.8-9
The study involved 116 adults and adolescents (aged 12 years or older) with severe haemophilia A or B without inhibitors. The primary efficacy measure was the annualised bleeding rate (ABR) of treated bleeds during treatment with marstacimab compared to ABR during the observational phase. 8-9
In the 33 patients receiving on-demand factor replacement during the first 6 months of the study, the estimated ABR was 38, compared to the estimated ABR with marstacimab treatment of only 3.2 (reduction by 92%). In the group of 83 patients who received routine prophylactic therapy during the 6-month observational please, the ABR was 7.85 compared to the ABR with marstacimab of 5.08. These results show that marstacimab is superior over on-demand factor replacement and not worse than prophylactic therapy.8-9
In people with haemophilia A, the average yearly rate of treated bleeds was about 9 with routine prophylaxis therapy compared with 5 with marstacimab. In people with haemophilia B, this rate was about 3 with routine prophylaxis therapy compared with about 5 with marstacimab. A long-term extension study showed that the rate in people with haemophilia B decreased further with continued treatment with marstacimab. 8
Imetelstat
Imetelstat is an oligonucleotide telomerase inhibitor, approved for adults with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia requiring four or more red blood cell units over 8 weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs). Imetelstat binds to the template region of the RNA component of human telomerase (hTR), inhibits telomerase enzymatic activity and prevents telomere binding. 11
Efficacy was evaluated in IMerge (NCT02598661), a randomised (2:1), double-blind, placebo-controlled multi-center trial in 178 patients with MDS. Patients received an intravenous infusion of imetelstat 7.1 mg/kg or placebo in 28-day treatment cycles until disease progression or unacceptable toxicity. Randomisation was stratified by prior red blood cell (RBC) transfusion burden and by International Prognostic Scoring System (IPSS) risk group. All patients received supportive care, which included RBC transfusions. 10-11
Efficacy was established after a median follow up time of 19.5 months (range: 1.4 to 36.2) in the imetelstat group and 17.5 months (range: 0.7 to 34.3) in the placebo group based upon the proportion of patients who achieved ≥ 8-week and ≥ 24-week RBC transfusion independence (RBC-TI), defined as the absence of RBC transfusion(s) during any consecutive 8 week period, and during any consecutive 24 week period, respectively, from randomisation until the start of subsequent anti-cancer therapy (if any). The rate of ≥ 8-week RBC-TI was 39.8% (95% CI: 30.9, 49.3) in the imetelstat group and 15% (95% CI: 7.1, 26.6) in the placebo group (p-value < 0.001). The rate of ≥ 24-week RBC-TI was 28% (95% CI: 20.1, 37) in the imetelstat group and 3.3% (95% CI: 0.4, 11.5) in the placebo group (p-value < 0.001). 10-11
Summary
In 2024, regulatory bodies across Europe, the US, and the UK—namely the EMA, FDA, and MHRA—approved 53 novel medicines, a decrease from the 70 approvals seen in 2023. 1
According to a review by Topouzis et al., 2025, there was an increased emphasis on the use of innovative pharmacological approaches. Among the most noteworthy approvals were medicines such as Zenocutuzumab for NRG1 fusion-positive cancers, Xanomeline for schizophrenia with a novel cholinergic mechanism, and Zanidatamab for HER2-positive biliary tract cancer. Additional breakthroughs included Marstacimab, a first-in-class therapy for haemophilia leveraging a new mechanism of clotting restoration, and Imetelstat, the first telomerase inhibitor approved for transfusion-dependent myelodysplastic syndromes.
These approvals highlight a broader trend toward precision medicine, orphan medicine development, and innovation in therapeutic design.
How Somerville Development Partners can help
We have expertise in navigating the special considerations required to bring novel medicines, ATMPs/cell and gene therapies to market, including taking scientific advice to understand regulatory requirements around some of the specific challenges.
We are well-versed in specific initiatives that may be applicable to your advanced therapy—initiatives such as the European Medicine Agency’s Priority Medicines Scheme (PRIME); or the UK’s Innovative Licensing and Access Pathway (ILAP).
You may be developing an advanced therapy for an ultra-rare disease, in which case, it may be feasible to obtain marketing under exceptional circumstances approval. We can advise the best route to approval for your unique product and development programme.
