In the first half of the year, the FDA approved a number of landmark drugs, and there are many highlights:
Rezdiffra, the first non-alcoholic steatohepatitis drug in 40 years, was approved for marketing. After 32 years, another cytokine drug for tumor immunotherapy, Anktiva, has been approved for marketing.
So far in the first half of 2024, the Center for Drug Evaluation and Research (CDER) has approved 18 new molecular entities, including 13 new chemical drugs and 5 new biological drugs.
New chemical drugs
It is worth mentioning that the number of new drug approvals in the first half of this year is significantly lower than last year, and more than 20 new molecular entities have been approved in the same period in 2023, mainly due to the decrease in the number of new chemical drugs on the market (17 new chemical drugs were listed in the same period last year).
| Trade name | Active ingredients | Indication | Company | Date of approval |
| Iqirvo | Elafibranor | Adult primary biliary cholangitis with inadequate ursodeoxycholic acid response | Ipsen Biopharm Ltd | 10-Jun-24 |
| Rytelo | Imetelstat | Transfusion dependent anemia in patients with low-risk myelodysplastic syndrome | Geron Corp | 6-Jun-24 |
| Xolremdi | Mavorixafor | WHIM syndrome | X4 Pharmaceuticals | 26-Apr-24 |
| Ojemda | Tovorafenib | Low grade glioma in children | Day One Biopharmaceuticals | 2-Apr-24 |
| Lumisight | Pegulicianine | Adjuvant detection during breast cancer surgery | Lumicell | 17-Apr-24 |
| Zevtera | CeftobiproleMedocaril Sodium | Multiple infection | Basilea Pharm Allsch | 3-Apr-24 |
| Voydeya | Danicopan | Extravascular hemolysis with paroxysmal sleep hemoglobinuria | Alexion Pharms Inc | 29-Mar-24 |
| Vafseo | Vadadustat | Anemia from chronic kidney disease | Akebia Therapeutics Inc | 27-Mar-24 |
| Duvyzat | Givinostat | Duchenne muscular dystrophy | Italfammaco Sa | 27-Mar-24 |
| Tryvio | Aprocitentan | Hypertension | Idorsia Pharma Ltd | 19-Mar-24 |
| Rezdiffra | Resmetirom | MASH | Madrigal | 14-Mar-24 |
| Exblifep | Cefepime, Enmetazobactam | Complex urinary tract infection, Pyelonephritis | Allecra Therapeutics Sas | 22-Feb-24 |
| Zelsuvmi | Berdazimer Sodium | Molluscum contagiosum | Lnhc | 5-Jan-24 |
From the perspective of approval methods, among the 13 approved new chemical drugs, 8 drugs such as Iqirvo, Xolremdi, and Ojemda have been listed through priority review, which needs to be completed within 6 months compared with 10 months for NDA standard approval, which saves the time and cost of enterprises, and the drugs under priority review have higher therapeutic value.
In terms of indications, there are 4 in the field of metabolic diseases, 3 in the field of oncology, 2 in the field of immunotherapy, 2 in the field of anti-infection, and 1 in each of the nervous system and other fields. Among the approved new chemical drugs, there are 6 orphan drugs, accounting for nearly half, which shows that the field of rare disease research and development is still hot.
The following is a brief introduction to several new chemical drugs that have been approved for marketing.
Iqirvo (Elafibranor)
On June 10, Ipsen announced that the United States FDA has accelerated approval of Iqirvo, a first-in-class, oral, once-daily peroxisome proliferative activating receptor (PPAR) agonist for the treatment of adults with primary biliary cholangitis (PBC) who have an inadequate response to UDCA, or as monotherapy for patients intolerant to UDCA.
This is the first new drug approved for the treatment of biliary cholangitis, a rare liver disease, in the past decade.
PBC is caused by chronic damage to the bile ducts, which leads to a decrease in the ability to remove toxins, leading to cirrhosis and liver failure. According to the results of the pivotal Phase 3 trial ELATIVE, only patients treated with elafibranor achieved normal alkaline phosphatase (ALP) at week 52, a 41% reduction compared to the control group. Research is currently underway to treat patients with rare autoimmune PBC and to treat inflammation, cholestasis, and fibrosis in PBC.
It is worth mentioning that Seladelpar, a drug with the same target, has been qualified for priority review by the FDA, and the results of the review are expected to be announced in August.
Rytelo (Imetelstat)
On June 6, Geron Corporation’s Rytelo was approved by the FDA for the treatment of transfusion-dependent anemia in patients with low-risk myelodysplastic syndrome (LR-MDS). MDS is a rare type of blood cancer that prevents blood (hematopoietic) stem cells from maturing into healthy blood cells. If a patient does not have enough healthy blood cells in their body, serious conditions such as anemia, frequent infections, and uncontrolled bleeding may occur.
Rytelo is a first-in-class telomerase inhibitor, Imetelstat regulates the apoptosis of malignant hematopoietic stem cells by binding to and inhibiting telomerase. Founded in 1990, it took more than 30 years for Geron to develop telomerase inhibitors to launch Rytelo, and after a series of failures, Imetelstat finally had a place in MDS. In the phase 3 IMerge study, the proportion of patients who did not need blood transfusions after Imetelstat treatment was significantly higher than that of the placebo group.
Xolremdi (Mavorixafor)
On April 26, X4 Pharmaceuticals announced that the United States FDA approved Xolremdi (mavorixafor) capsules for the treatment of patients 12 years and older with WHIM syndrome to increase the number of mature neutrophils and lymphocytes in the blood circulation. This is the first approved small molecule therapy for patients with WHIM syndrome. WHIM syndrome is a rare primary immunodeficiency and chronic neutropenia caused by a disruption of the CXC chemokine receptor 4 (CXCR4) signaling pathway.
Xolremdi is a selective CXCR4 antagonist, and results from the pivotal Phase 3 4WHIM study showed that Xolremdi treatment significantly increased the duration of neutrophil count (ANC) levels above the threshold (≥500 cells/μl) and absolute lymphocyte count (ALC) levels above the threshold (≥1000 cells/μl) compared with placebo, with a favorable safety profile.
Previously, Xolremdi had been granted Breakthrough Therapy Designation by the FDA.
Ojemda (Tovorafenib)
On April 23, the FDA granted accelerated approval to Ojemda (tovorafenib), a pan-RAF kinase inhibitor developed by Day One Biopharmaceuticals, for the treatment of patients with relapsed or refractory pediatric low-grade glioma (pLGG) 6 months of age or older who have BRAF fusions or rearrangements, or BRAF V600 mutations. Ojemda, a systemic therapy for the treatment of the disease, is able to inhibit the growth of tumors carrying BRAF fusions or BRAF V600 mutations and is brain penetrant. It was previously granted Breakthrough Therapy and Rare Pediatric Disease Designation by the FDA, which is one of the reasons for the approval based on data from the Phase 2 clinical trial of FIREFLY-1.
Pediatric low-grade glioma is the most common brain tumor in children, and the annual incidence of LGG in children is 1.3~2.1 cases per 100,000 people in the United States, and it is estimated that there will be 1000-1600 new cases per year. On March 16, 2023, the FDA approved Novartis’ BRAF/MEK combination, Tafinlar (dabrafenib) in combination with Mekinist (trametinib), which is the first targeted therapy for pLGG.
Rezdiffra (Resmetirom)
On March 14, the FDA approved Madrigal’s oral small molecule drug Rezdiffra for the treatment of adult patients with metabolic dysfunction-associated steatohepatitis with moderate to advanced liver scarring (fibrosis), in combination with diet and exercise. This is the first MASH drug approved for marketing in 40 years.
Resmetirom is a thyroid hormone receptor (THR)-β oral selective agonist. THR-β is highly expressed in the human liver and can regulate lipid metabolism, reduce LDL-C, triglycerides, and atherogenic lipoproteins, THR-β can also reduce lipotoxicity and improve liver function by promoting the breakdown of fatty acids and stimulating mitochondrial biogenesis, thereby reducing liver fat.
New biological drugs
| Trade name | Active ingredients | Indication | Company | Date of approval |
| Imdelltra | Tarlatamab-Dlle | Non-small cell lung cancer | Amgen | 16-May-24 |
| Anktiva | Nogapendekin Alfa Inbakicept-PmIn | Non-muscular invasive bladder cancer | Altor Bioscience | 22-Apr-24 |
| Winrevair | Sotatercept-Csrk | Pulmonary hypertension | Merck | 26-Mar-24 |
| Tevimbra | Tislelizumab | Esophageal squamous cell carcinoma | Beigene | 13-Mar-24 |
| Letybo | Letibotulinumtoxina-Wlbg | Moderate to severe interglabellar lines in adults | Hugel Inc | 29-Feb-24 |
To date, in the first half of 2024, CDER has approved a total of five new biological drugs, including one bisspecific antibody (Imdelltra), one cytokine drug (Anktiva), one fusion protein (Winrevair), one monoclonal antibody (Tevimbra), and one neurotoxin (Letybo).
From the perspective of therapeutic areas, among the five new biological drugs approved, the largest proportion is in the field of cancer treatment, with three new drugs on the market, Imdelltra, Anktiva, and Tevimbra, and it is worth noting that Tevimbra (tislelizumab) of Chinese innovative pharmaceutical company BeiGene successfully landed in the United States market and became the second PD-1 drug marketed in the United States. In the field of metabolism, there is Winrevair, and there is also a medical aesthetic drug Letybo on the market.
Anktiva
On April 22, Immunity Bio announced that the FDA has approved Anktiva in combination with Bacillus Calmette-Guérin (BCG) for the treatment of patients with non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papilloma, becoming the world’s first approved interleukin-15 (IL-15) drug, which is another cytokine drug approved by the United States FDA for tumor immunotherapy after 32 years, and the third in history.
Anktiva is an IL-15 superagonist complex consisting of an IL-15 mutant that binds to the IL-15Rα sushi domain, which allows it to activate downstream signaling pathways without trans-presentation like native IL-15, and the IgG1-Fc fragment greatly prolongs the drug half-life.
Winrevair
On March 26, the FDA approved the marketing application of Merck & Co., Ltd. Winrevair for the treatment of pulmonary arterial hypertension (PAH), which is caused by the imbalance of promoting and inhibiting proliferative signals, resulting in thickening of blood vessels in the pulmonary artery wall, restricting blood flow, increasing the burden on the right side of the heart, and eventually leading to heart failure.
Winrevair is the first approved activin signaling inhibitor therapy for PAH, with an annual cost of $242,000 and an estimated peak annual sales of $7.5 billion.
| Trade name | Active ingredients | Indication | Company | Date of approval |
| Mresvia | Respiratory syncytial virus vaccine (RSV) | Prevention of lower respiratory tract diseases caused by respiratory syncytial virus in people aged 60 years and older | ModernaTX, Inc. | 31-May-24 |
| Beqvez | Elaparvovec-Dzkt | Moderate to severe hemophilia B | Pfizer | 26-Apr-24 |
| Cobas Malaria | Cobas MalariaTest For Use OnThe Cobas 6800/8800 Systems | Malaria detection | Roche Molecular Systems | 19-Mar-24 |
| Elecsys Anti-HCV II | Elecsys Anti-HCV II | Hepatitis C virus antibody testing | Roche Diagnostics | 28-Feb-24 |
| Elecsys Anti-HBc II | Elecsys Anti-HBc II | Hepatitis B core antigen antibody detection | Roche Diagnostics | 27-Feb-24 |
| Elecsys HBsAg II and ElecsysHBSAg II Auto Confirm | Elecsys HBsAg II and ElecsysHBSAg II Auto Confirm | Hepatitis B surface antigen detection | Roche Diagnostics | 21-Feb-24 |
| Amtagvi | lifileucel | Adult patients with skin cancer | lovance Biotherapeutics, Inc. | 16-Feb-24 |
| Elecsys Chagas | Elecsys Chagas | Trypanosoma cruzi antibody detection | Roche Diagnostics | 5-Feb-24 |
| Source Plasma | Source Plasma | / | Life Plasma, Inc. | 30-Jan-24 |
To date, CBER has approved nine biologics, including an RSV vaccine (Mresvia), a gene therapy (Beqvez), a cell therapy (Amtagvi), and a number of disease diagnostic technologies and blood products.
Beqvez (Elaparvovec-Dzkt)
On April 26, Pfizer announced that the FDA has approved Beqvez, a gene therapy based on an adeno-associated virus (AAV) vector, for the treatment of adults (18 years of age and older) with moderate to severe hemophilia B. Beqvez is priced at $3.5 million and can produce its own clotting factor IX protein in a one-time treatment, while the current standard of care requires regular infusions of clotting factor IX.
Amtagvi (Lifileucel)
On Feb. 16, Iovance Biotherapeutics announced that the FDA has granted accelerated approval to Amtagvi, a tumor-infiltrating lymphocyte (TIL) treatment option for the treatment of advanced melanoma that has progressed after PD-1/PD-L1 therapy.
Lifileucel is the world’s first approved TIL cell therapy, which isolates infiltrating lymphocytes from tumor cells, expands them in vitro and infuses them back into patients like CAR-T therapy, and can specifically recognize the patient’s tumor cells for killing. According to the readout results from the C-144-01 study, 31.5% of the 73 patients in Cohort 4 achieved objective response.
Summary
In the first half of this year, anti-tumor, autoimmunity, metabolism, anti-infection and rare diseases among the new drugs approved by the United States FDA are still hot areas, and the proportion of tumor drugs has increased significantly compared with last year, which shows that tumor drugs are still hot spots in drug research and development.
With the encouragement of the FDA’s policy, it can be seen that pharmaceutical companies are still enthusiastic about the research and development of drugs for the treatment of rare diseases, and the breakthroughs in the field of MASH therapy and the approval of a number of FIC drugs are also gratifying.
The breakthrough continues, and the second half of 2024 will be no less extraordinary. On June 11, Eli Lilly’s Alzheimer’s drug donanemab was unanimously approved by the Drug Advisory Committee by a vote of 11:0 for the drug’s effectiveness, and it is expected to be approved for marketing soon.
In addition, we will wait and see which drugs will be approved by the FDA!