On the agenda for the FDA this month are two RNA-based treatments for rare diseases.
March is shaping up to be a busy month for the FDA, with nearly ten target action dates across a wide variety of disease areas. The more highly anticipated verdicts due this month include a next-generation antibiotic for urinary tract infection and two RNA interference therapies.
Read below for more.
Scienture Targets First Liquid Losartan Approval
Scienture is advancing a liquid formulation of the popular blood pressure drug losartan, for which the FDA has a target action date of March 17.
The asset, dubbed SCN-102, is being proposed for the treatment of hypertension and to lower blood pressure both in adults and in children aged 6 and older. Scienture’s New Drug Application also covers the use of SCN-102 to reduce the likelihood of stroke in patients with hypertension and left ventricular hypertrophy, and to treat diabetic nephropathy in type 2 diabetes.
To back its application, Scienture filed Phase I pharmacokinetic data demonstrating that SCN-102 achieves “close comparability” to immediate-release tablets in terms of losartan exposure. Additionally, compared with the pill form of losartan, SCN-102 achieved peak concentration earlier, an outcome that is “expected” due to its liquid formulation, as per the company’s SEC document.
If approved, SCN-102 will be the first liquid formulation of losartan to hit the market, according to Scienture.
Elevar Eyes First-Line Nod in Liver Cancer
By March 20, the FDA is set to release its verdict on Elevar Therapeutics’ investigational VEGF tyrosine kinase inhibitor rivoceranib, which the biotech is proposing for the first-line treatment of unresectable or metastatic hepatocellular carcinoma. Elevar is combining rivoceranib with the PD-1 inhibitor camrelizumab.
Rivoceranib’s data package includes findings from the Phase III CARES-310 trial, a May 2024 readout that showed the rivoceranib combo resulted in significantly longer median overall survival than sorafenib alone. The study also noted progression-free survival, treatment response and duration of response benefits in patients treated with camrelizumab plus rivoceranib.
Elevar first tried to secure approval for rivoceranib in 2023, which ended in a rejection in May 2024. In its Complete Response Letter, the FDA pointed to manufacturing problems at a third-party provider, as well as incomplete clinical site inspections brought about by FDA travel restrictions. Elevar resubmitted its application in September 2024.
Alnylam’s RNAi Therapy for ATTR-CM Nears Judgment Day
One of the most highly anticipated FDA decisions this month is for Alnylam Pharmaceuticals, which is seeking to expand the label of its RNAi therapy vutrisiran to include transthyretin amyloidosis (ATTR) with cardiomyopathy. The FDA’s decision is due on March 23.
Vutrisiran is approved under the brand name Amvuttra, though its use is limited to the treatment of polyneuropathy of hereditary ATTR. The drug works by targeting and knocking down both the wildtype and mutant forms of the transthyretin RNA, in turn lowering the expression of the protein. As per Alynlam, this mechanism of action allows vutrisiran to address the underlying pathological cascade of ATTR and its cardiomyopathy manifestations.
Alnylam’s bid for label expansion is backed by the HELIOS-B study, data from which were published in the New England Journal of Medicine in August 2024. Results showed a 28% and 33% drop in the risk of death from any cause and recurrent cardiovascular events, respectively, after vutrisiran treatment.
If approved, vutrisiran will be the first treatment cleared for both the polyneuropathy and cardiomyopathy manifestations of ATTR, according to Alnylam.
Theratechnologies Tries Again for HIV Lipodystrophy Drug
After suffering a rejection last year, Theratechnologies is once again awaiting the FDA’s verdict for its F8 formulation of tesamorelin, a peptide therapy that the biotech is proposing for the reduction of stomach fat in people with HIV and lipodystrophy. The regulator’s decision is expected on March 25.
In its Complete Response Letter, the FDA pointed to problems related to tesamorelin’s chemistry, manufacturing and controls, particularly with impurities and the stability of the drug. In its resubmission, filed in November 2024, Theratechnologies said it had addressed the FDA’s concerns and provided additional data regarding tesamorelin’s immunogenicity risk.
Tesamorelin works by mimicking the growth hormone-releasing factor, promoting the secretion of growth hormone and, in turn, facilitating the breakdown of abdominal fat. The drug was first approved in 2010 and an F4 formulation, which is four times as concentrated as the original product, was given the go-ahead in 2018. Theratechnologies’ drug application is seeking approval for a formulation that is eight times stronger than the initial product.
GSK Pushes First-in-Class Antibiotic for Uncomplicated UTI
By March 26, the FDA is scheduled to release its verdict on GSK’s investigational antibiotic gepotidacin for the treatment of uncomplicated urinary tract infections in adult women and adolescents 12 years and up weighing at least 40 kg.
Gepotidacin is a first-in-class triazaacenaphthylene antibiotic that works by targeting and preventing the replication of bacterial DNA by binding to a unique site. Because gepotidacin utilizes a novel mechanism to target bacteria, it has shown activity against most uropathogens such as E. coli and S. saprophyticus, as well as N. gonorrhoeae, including strains that have become resistant to currently available treatments.
GSK is backing its application with data from the Phase III EAGLE-2 and EAGLE-3 studies, which in April 2023 found gepotidacin to be non-inferior to a current first-line treatment option, nitrofurantoin. EAGLE-2, for instance, demonstrated a 50.6% treatment success rate in patients given gepotidacin versus 47% in nitrofurantoin counterparts. The respective success rates in EAGLE-3 were 58.5% and 43.6%.
Milestone Proposes Tachycardia Nasal Spray
Milestone Pharmaceuticals’ lead pipeline asset is Cardamyst, an etripamil nasal spray the biotech is developing for the treatment of paroxysmal supraventricular tachycardia (PSVT). The FDA is expected to release its decision on Cardamyst by March 27.
In October 2023, when the FDA accepted Milestone’s first new drug application for Cardamyst, the biotech said it had submitted “the largest data package ever studied in PSVT.” The company at the time had filed what it called a “comprehensive data package” suggesting that its investigational calcium channel blocker was “twice as effective and three times as fast as placebo” in normalizing heart rhythm.
Despite an extensive evidence base, however, the FDA in December 2023 hit Milestone with a Refusal to File letter for Cardamyst, noting that the company’s filing was not sufficient to a warrant a full review. Milestone refiled its drug application in March 2024, which the FDA accepted in May of the same year.
After Delay, Soleno’s Prader-Willi Drug Nears Regulatory Decision
The FDA is scheduled to release its verdict on Soleno Therapeutics’ investigational Prader-Willi syndrome (PWS) drug diazoxide choline by March 27.
Soleno’s diazoxide choline drug is an extended-release formulation of diazoxide, which has long been used to treat various rare diseases, though the molecule has yet to be cleared for PWS, according to the biotech. Soleno’s drug application, which it filed in June 2024, is supported by Phase III data pointing to the candidate’s potential in addressing hyperphagia and other hallmark symptoms of PWS, including aggressive behaviors and fat buildup.
Soleno also submitted findings from five Phase I studies in healthy volunteers and three Phase III trials.
In November 2024, the biotech announced that the FDA needed more time to review its application for diazoxide choline, especially following the company’s responses to certain information requests. The regulator considered these additional submissions as major amendments to the drug application and pushed its deadline back by three months.
Sanofi, Alnylam Hope for Hemophilia Approval for RNAi Therapy
Alnylam’s second showing on this list is for its Sanofi-partnered siRNA therapy fitusiran, which the companies proposed for the treatment of hemophilia A and B. The FDA’s verdict is expected on March 28.
To back the RNAi therapy, Sanofi and Alnylam ran the ATLAS clinical development program, publications from which went live in The Lancet and The Lancet Hematology in April 2023. In one study, dubbed ATLAS-INH, fitusiran treatment resulted in zero monthly bleeding episodes in 66% of patients who were also on factor VIII inhibitors. The other study, called ATLAS A/B, found that in patients without inhibitors, 51% achieved zero monthly bleeds after fitusiran.
Fitusiran is given via an injection under the skin and works by binding to and lowering the expression of antithrombin, a protein that inhibits clotting.
