FDA March Approvals Loom: GSK, Sanofi, Alnylam, and Others Await Pivotal Decisions on Novel Therapies

March is a busy month for the U.S. FDA, with nearly a dozen drug approval decisions expected to be announced. These drugs cover a variety of disease areas, including a new generation of antibiotics for urinary tract infections and two RNA interference therapies. Below are some of the key approval updates that have garnered significant attention this month:

Scienture, Inc. Poised for First Approval of Liquid Losartan

Scienture, Inc. is advancing a product named SCN-102.LosartanLiquid dosage form, the FDA approval result is expected to be announced on March 17.Intended for the treatment of hypertension in adults and children aged 6 years and above, to lower blood pressure. Additionally, the new drug application for SCN-102 also includes reducing the risk of stroke in patients with hypertension and left ventricular hypertrophy, as well as treating diabetic nephropathy in type 2 diabetes.

Phase I pharmacokinetic data submitted by Scienture showed that SCN-102 was "very similar" to the immediate-release tablet in terms of losartan exposure. Additionally, according to the company’s filing with the U.S. Securities and Exchange Commission, SCN-102 reached peak concentration earlier than the pill form of losartan, which is an expected effect of a liquid formulation. If approved, SCN-102 would become the first liquid formulation of losartan to reach the market.

Elevar's First-Line Treatment for Liver Cancer Awaits Approval

On March 20, the FDA will make a decision on Elevar Therapeutics' investigational vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor rivoceranib. The company proposed its combination with the PD-1 inhibitor camrelizumab as a first-line treatment for unresectable or metastatic hepatocellular carcinoma.

Data on rivoceranib include results from the Phase 3 CARES-310 trial. The trial results, published in May 2024, showed that combination therapy with rivoceranib significantly extended median overall survival compared to sorafenib alone. The study also noted that patients receiving camrelizumab plus rivoceranib experienced benefits in progression-free survival, treatment response, and duration of response.

Elevar Therapeutics made its first attempt to gain approval for rivoceranib in 2023, but was rejected in May 2024. In the Complete Response Letter, the FDA pointed out that there were manufacturing issues with a third-party supplier and that inspections of clinical trial sites were incomplete due to the FDA's travel restrictions. Elevar Therapeutics resubmitted the application in September 2024.

Alnylam's RNAi Therapy Nears Approval

One of the most anticipated FDA decisions this month,It is about Alnylam Pharmaceuticals' RNAi therapy vutrisiran.n。The company is seeking to expand the label applicability of vutrisiran to include transthyretin amyloidosis (ATTR) with cardiomyopathy, and the FDA will make a decision on March 23.

Vutrisiran, marketed under the brand name Amvuttra, has been approved for marketing and is currently indicated only for the treatment of polyneuropathy caused by hereditary ATTR. The drug works by targeting and reducing both wild-type and mutant transthyretin RNA, thereby decreasing protein expression. Alnylam Pharmaceuticals stated that this mechanism of action enables vutrisiran to address the underlying pathological cascade of ATTR and its cardiomyopathy manifestations.

Alnylam’s application to expand the label is based on the HELIOS-B study, with data published in The New England Journal of Medicine in August 2024. Results showed that treatment with vutrisiran reduced the risk of death from any cause and recurrent cardiovascular events by 28% and 33%, respectively. If approved, vutrisiran would become the first drug authorized for treating both polyneuropathy and cardiomyopathy manifestations of ATTR.

Theratechnologies Makes Another Push for HIV Lipoatrophy Drug Approval

Theratechnologies’ peptide therapy tesamorelin, formulated as F8, aims to reduce abdominal fat in patients with HIV and lipodystrophy. After being rejected last year, the company is again awaiting an FDA decision, with results expected on March 25.

FDA’s Complete Response Letter indicated that there were issues with tesamorelin in the areas of chemistry, manufacturing, and controls, particularly regarding impurities and drug stability. When Theratechnologies Inc. resubmitted the application in November 2024, it stated that it had addressed the FDA's concerns and provided additional data on the immunogenicity risk of tesamorelin.

Tesamorelin promotes the secretion of growth hormone by mimicking the growth hormone-releasing factor, thereby facilitating the breakdown of abdominal fat. The drug was first approved in 2010, and the F4 formulation, which has four times the concentration of the original product, was approved in 2018. Theratechnologies Inc. is now applying for approval of a formulation with eight times the concentration of the initial product.

GSK's New Antibiotic Gepotidacin Expected to Gain Approval

On March 26, the FDA will make a decision on GSK's investigational antibiotic gepotidacin, which is used to treat uncomplicated urinary tract infections in adult women and adolescents aged 12 years and older who weigh at least 40 kilograms.

Gepotidacin is a first-in-class triazacenaphthylene antibiotic that targets and inhibits bacterial DNA replication by binding to a unique site. Due to its novel mechanism of action targeting bacteria, it is active against most urinary tract pathogens (such as E. coli, Staphylococcus saprophyticus, and Neisseria gonorrhoeae), including strains resistant to existing treatments.

GSK's submission of Phase 3 EAGLE-2 and EAGLE-3 study data supports its application. The April 2023 study found that gepotidacin was non-inferior to the current first-line treatment drug nitrofurantoin in therapeutic efficacy. For instance, in the EAGLE-2 trial, the treatment success rate was 50.6% for patients receiving gepotidacin and 47% for the nitrofurantoin group; in the EAGLE-3 trial, the success rates were 58.5% and 43.6%, respectively.

Milestone's PSVT Nasal Spray Cardamyst Awaiting Approval

Milestone Pharmaceuticals' lead investigational product is Cardamyst, or etripamil nasal spray, for the treatment of paroxysmal supraventricular tachycardia (PSVT). The FDA is expected to make a decision on Cardamyst by March 27.

In October 2023, the FDA accepted Milestone Pharmaceuticals' initial new drug application for Cardamyst, which the company claimed included "the largest dataset in PSVT studies." At the time, the company submitted a "comprehensive dataset" showing that its investigational calcium channel blocker was "twice as effective as placebo in restoring normal heart rhythm and three times faster."

However, despite substantial evidence, the FDA issued a refusal-to-file letter to Milestone Pharmaceuticals in December 2023, stating that the documentation submitted by the company was insufficient for a comprehensive review. Milestone resubmitted the drug application in March 2024, and the FDA accepted it for review in May of the same year.

Soleno Therapeutics' Drug for Prader-Willi Syndrome Nears Approval

On March 27, the FDA will make a decision on Soleno Therapeutics' Prader-Willi Syndrome (PWS) drug, diazoxide choline.

Soleno's diazoxide choline is a sustained-release formulation.Diazoxide,This molecule has long been used to treat various rare diseases but has not yet been approved for PWS. The drug application submitted by Soleno in June 2024 is based on Phase 3 data, which indicate that the candidate drug has the potential to address hallmark symptoms of PWS, including hyperphagia, aggressive behavior, and fat accumulation.

Soleno also submitted the results of five Phase I studies in healthy volunteers and three Phase III trials. In November 2024, the company announced that the FDA needed more time to review its application for diazoxide choline, particularly after the company responded to certain information requests. The FDA considered these additional submissions as significant amendments to the drug application and postponed the approval deadline by three months.

Sanofi and Alnylam’s Hemophilia RNAi Therapy Fitusiran Awaits Approval

Alnylam Pharmaceuticals is back, this time with fitusiran, an siRNA therapy developed in collaboration with Sanofi. The two companies propose its use for treating hemophilia A and B. The FDA is expected to make a decision by March 28.

To support this RNAi therapy, Sanofi and Alnylam launched the ATLAS clinical development program, with related research findings published in *The Lancet* and *The Lancet Haematology* in April 2023. In a study named ATLAS-INH, 66% of patients receiving fitusiran treatment while using Factor VIII inhibitors experienced zero bleeding episodes per month. Another study, named ATLAS A/B, found that among patients not using inhibitors, 51% had zero bleeding episodes per month after receiving fitusiran treatment.

Fitusiran is administered via subcutaneous injection and works by binding to antithrombin and reducing its expression, a protein that inhibits blood coagulation.

This month, the FDA's drug approval decisions for numerous companies will have a significant impact on the treatment of rare diseases, cancer, cardiovascular diseases, infectious diseases, and other fields. Relevant companies and patients are closely watching these rulings.