5 Novel FDA Approvals Notched in 2024

 

Among the 55 novel drugs that crossed the regulatory finish line last year were notable new mechanisms of action, coming particularly in the oncology and neurosciences spaces.

The FDA approved 55 novel medicines in 2024—some first-in-class and others representing the first new mechanism of action for an indication in decades.

Novel approvals last year ran the therapeutic gamut from cardiovascular and hematological to infectious diseases, with some of the most significant new mechanisms of action found in oncology and neuroscience.

Top of mind is Bristol Myers Squibb’s Cobenfy, which the FDA greenlit in September as the first novel schizophrenia treatment in 35 years. Going back to February, we saw the approval of Iovance’s Amtagvi, the first one-time cell therapy for a solid tumor and the first tumor-infiltrating lymphocytes (TIL) therapy. Amtagvi is indicated for advanced melanoma, which has been notoriously difficult to treat. Another notable milestone was the March approval of Madrigal Pharmaceuticals’ Rezdiffra, the first therapy to get the FDA’s nod for metabolic dysfunction-associated steatohepatitis (MASH).

Here’s a look at five of the year’s most notable novel approvals.

Iovance’s Amtagvi Jumpstarts TIL Space

In February 2024, the FDA granted accelerated approval to Iovance Biotherapeutics for Amtagvi to treat patients with advanced melanoma. Forty years in the making, TIL therapies take advantage of the patient’s own immune cells—lymphocytes—which tend to be suppressed in the tumor environment. These cells are extracted from tumor biopsies, expanded in numbers or revamped for better efficacy, then transfused back into the patient, leading to antitumor activity.

Iovance supported its Biologics License Application for Amtagvi with clinical data showing a 31% objective response rate with a median duration of response not reached at 18.6 months of follow-up; 42% of responses lasted for two years or longer.

While CAR T therapies have transformed treatment for blood cancers, their performance hasn’t been as impressive against solid tumors. Part of the attraction of TIL therapies is their ability to recognize multiple antigens simultaneously, something CAR Ts are unable to do. Conventional CAR Ts can only recognize a small number of proteins on the surface of tumor cells, while TILs can identify tumor targets derived from intra- or extracellular tumor proteins, Sammy Farah, CEO of Turnstone Biologics, told BioSpace in February. Because solid tumors are known to be heterogeneous, TILs are likely to be successful as a treatment modality, Farah said.

With more than 75 TIL immunotherapies in preclinical or clinical studies for various indications, numerous players are coming up behind Iovance. Turnstone Biologics is developing TIL therapies for colorectal cancers, head and neck squamous cell carcinoma and uveal melanoma, while Instil Bio is working on TILs for non-small cell lung cancer and other solid tumors. Bristol Myers Squibb and Incyte Corporation are also active in this space.

Adaptimmune’s Tecelra Succeeds Against Synovial Sarcoma

Also in the cell therapy space, Adaptimmune Therapeutics in August 2024 secured FDA approval for the first engineered T cell therapy for solid tumor cancers in the U.S. Tecelra is also the first new therapeutic option for synovial sarcoma—a rare soft tissue cancer—in more than 10 years. Like Amtagvi, Tecelra was approved under the FDA’s accelerated pathway.

Also similar to Amtagvi, Tecelra leverages the patient’s immune cells and modifies them to be able to target cancer cells. Tecelra is specifically designed to recognize and attack the melanoma-associated antigen A4 (MAGE-A4) protein, which is crucial to preventing cell cycle arrest and cell death. MAGE-A4 is commonly overexpressed in solid tumors, especially synovial sarcoma.

The FDA’s approval was based on results of the SPEARHEAD-1 study, in which treatment with Tecelra led to an overall response rate of 43%. A complete response was reported in 4.5% of patients. Treatment response lasted for at least 12 months in 39% of study participants who were responsive to the therapy.

Bristol Myers Squibb’s Cobenfy Breaks Through Against Schizophrenia

On the neuro front was the FDA’s approval of Bristol Myers Squibb’s Cobenfy in September. A first-in-class muscarinic agonist, Cobenfy comprises two separate drugs with distinct mechanisms of action: xanomeline activates M1 and M4 muscarinic receptors to reduce schizophrenia symptoms, while trospium reduces potential side effects of such activation, such as cardiovascular issues and increased production of saliva and tears. Dopamine-based drugs come with side effects such as weight gain and drowsiness. Targeting the muscarinic pathway may avoid such issues because these receptors are not expressed in key brain regions, Carlos Dortrait, SVP and general manager of U.S. immunology and neuroscience at BMS, told BioSpace in September.

BMS supported Cobenfy’s application with data from three registrational studies. EMERGENT-1 and EMERGENT-2 established the drug’s efficacy in treating schizophrenia on the Positive and Negative Syndrome Scale, and EMERGENT-3 showed that the therapy, then called KarXT, could significantly reduce overall symptom severity.

While Cobenfy proved the potential of targeting the muscarinic pathway in schizophrenia, the mechanism was called into question not two months later when AbbVie’s emraclidine failed to show efficacy in two Phase II clinical trials for the neuropsychiatric disease. The difference might lay in the M1 receptor, Stifel analysts suggested in November. While Cobenfy acts on both the M1 and M4 receptors, emraclidine only targets M4. “There’s been a longstanding thesis that M1 may contribute to efficacy on cognition,” the analysts wrote.

If true, this would be bad news for Neurocrine Biosciences, which is developing a muscarinic M4 selective agonist, NBI-1117568. The San Diego–based company announced results from a mid-stage trial of the candidate in August 2024, showing that the lowest dose of NBI-1117568 improved symptoms of schizophrenia. All other doses failed to meet the study’s primary endpoint.

Roche’s Tecentriq Hybreza Provides Flexible Treatment Option

Also in September, the FDA greenlit the first subcutaneous PD-(L)1 blocker in the U.S., Roche’s Tecentriq Hybreza. Approved for the same indications as intravenous Tecentriq—including skin, liver, lung and soft-tissue cancers—the subcutaneous formulation leverages Halozyme Therapeutics’ Enhanze technology, which uses a recombinant enzyme to digest hyaluronan proteins beneath the skin to improve fluid flow in the subcutaneous space. This effect allows large volumes of the liquid Tecentriq to be injected under the skin, while also boosting the medicine’s dispersion and absorption.

Tecentriq Hybreza “can treat patients faster and in more accessible settings” and “offers patients with multiple cancer types and their physicians greater flexibility and choice of treatment administration,” Roche CMO Levi Garraway said in a statement following the approval.

The subcutaneous formulation is administered in approximately seven minutes, while an intravenous infusion of Tecentriq usually takes 30 minutes to 60 minutes, according to Roche.

Approval of Tecentriq Hybreza was based partly on the Phase Ib/III IMscin001 study, in which the subcutaneous injection reached comparable levels of the drug in the blood as its intravenous formulation, with similar safety and efficacy profiles.

ARS Pharmaceuticals’ Neffy First Nasal Spray for Severe Allergies

People living with severe allergic reactions that could lead to anaphylaxis got a new, more palatable treatment option in August when the FDA approved ARS Pharmaceuticals’ Neffy as the first nasal spray for the condition. The first epinephrine product for the treatment of anaphylaxis that is not administered by injection, Neffy is a single-dose nasal spray administered into one nostril. A second dose may be administered if there is no improvement in symptoms or symptoms worsen, according to the FDA’s approval announcement.

“Anaphylaxis is life-threatening and some people, particularly children, may delay or avoid treatment due to fear of injections,” Kelly Stone, associate director of the Division of Pulmonology, Allergy and Critical Care in the FDA’s Center for Drug Evaluation and Research, said in a statement. “The availability of epinephrine nasal spray may reduce barriers to rapid treatment of anaphylaxis.”

Neffy’s approval was supported by four studies in 175 healthy adults without anaphylaxis, which showed comparable epinephrine blood concentrations between the nasal spray and approved epinephrine injection products. Neffy also led to similar increases in blood pressure and heart rate as epinephrine injection products did. These physiological changes are critical effects of epinephrine in the treatment of anaphylaxis, according to the FDA.

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