Top 5 Most Promising FDA New Drug Approvals Expected in the Second Half of 2024

Top 5 Most Promising FDA New Drug Approvals Expected in the Second Half of 2024

The FDA is reviewing applications for several highly anticipated drugs for approval in 2024. These include an innovative new treatment for schizophrenia, a heart disease drug and oncology drugs.

In 2023, the US Food and Drug Administration (FDA) approved a record-breaking 61 drugs, the most in history. While it isn’t known whether 2024 might beat that record, it will surely be a busy year for the agency.

Since January, the FDA has already signed off on more than a dozen novel drugs.

Among these are Madrigal Pharmaceuticals’ resmetirom (branded Rezdiffra), which secured FDA approval in March for the treatment of nonalcoholic steatohepatitis (NASH) and sotatercept (commercial name Winrevair) for pulmonary hypertension (PAH).

The agency is reviewing applications for several highly anticipated drugs for approval in 2024. These include an innovative new treatment for schizophrenia, a heart disease drug and oncology drugs.

Some treatments already on the market have grabbed additional approvals in 2024, including Novo Nordisk’s Wegovy (semaglutide) for cardiovascular risk reduction, Dupixent (dupilumab) for eosinophilic esophagitis (EoE) in young children and Xolair (omalizumab) for food allergies.

As the FDA accepts more new drug applications for review throughout the year, additional decision dates may be scheduled later in 2024.

The Prescription Drug User Fee Act (PDUFA) date is the deadline that the FDA sets for reviewing a New Drug Application (NDA) or Biologics License Application (BLA) and making a final decision on marketing approval.

The review period is typically ten months after the agency accepts a drug application. Applications accepted under the Priority Review pathway have a shortened review period of six months from the time of application acceptance.

According to pharma commercial intelligence and predictive analytics company Evaluate, which releases a list of the most highly anticipated drugs of the year, the top med on the list is an unexpected one that could make big waves.

Here are the top five FDA new drug approvals in the second half of 2024 to look out for based on Evaluate’s 2024 preview report. The top ten list included drugs already approved such as resmetirom and sotatercept.


1.   Schizophrenia Drug KarXT

Maker: Karuna Therapeutics

PDUFA: September 26, 2024

Estimated 2028 revenue: $2.8 billion

After Bristol Myers Squibb’s (BMS) blockbuster acquisition of neurology biotech Karuna Therapeutics in the last quarter of 2023, the company is awaiting for the deal to pay off with Karuna’s lead asset KarXT (xanomeline-trospium), which is currently under FDA review.

BMS made the deal, which was completed in March this year, to expand its neuroscience portfolio with KarXT along with Karuna’s early-stage and pre-clinical pipeline.

According to Evaluate, KarXT’s approval is the most anticipated new drug approval in 2024. The firm predicts sales of KarXT could reach $2.8 billion.

KarXT is an antipsychotic with a novel mechanism of action (MoA) and “differentiated efficacy and safety,” according to BMS. The drug is a first-in-class M1/M4 muscarinic receptor agonist that works to help reduce symptoms of psychosis and minimize or eliminate potential side effects. The drug’s novel MoA contrasts current drugs for schizophrenia and similar disorders, which focus on blocking dopamine or serotonin receptors.

Worldwide, approximately 24 million people suffer from schizophrenia. The condition has significant unmet need with only a handful of treatments available that have significant side effects such as drowsiness and weight gain. It is estimated that only 20 percent of schizophrenia patients are considered “well treated.”

Current drugs on the market for schizophrenia include Lundbeck and Otsuka’s Rexulti (brexpiprazole) and Eli Lilly’s Prozac (fluoxetine), but these drugs derive the majority of their sales from other conditions, including severe forms of depression or Alzheimer’s agitation.

Compared to existing medications, KarXT boasts a strong efficacy profile with minimal side effects. Karuna’s FDA submission, made in September 2023, included data from one Phase II and two Phase III placebo-controlled trials.

In the Phase III EMERGENT-3 trial, compared to placebo, KarXT led to a 9.6-point greater reduction in the Positive and Negative Syndrome Scale (PANSS), the clinical standard for measuring the severity of schizophrenia symptoms. The trial also met all of its secondary endpoints in favor of KarXT over placebo, with a lack of weight gain and drowsiness as side effects, which serves as a major advantage for BMS over current drugs. Results of the study are published in The Lancet. Karuna also has ongoing long-term extension trials.


2.   Alzheimer’s Hopeful Donanemab

Maker: Eli Lilly

PDUFA: Beyond first quarter of 2024

Estimated 2028 revenue: $2.2 billion

After Biogen and Eisai’s Aduhelm (aducanumab) and Leqembi (lecanemab), donanemab is Eli Lilly’s answer in the beta-amyloid-lowering class of monoclonal antibodies. The therapy is Evaluate’s second most anticipated drug approval for 2024. It is a top pick despite the controversies around Aduhelm, which was pulled by Biogen last month, and Leqembi due to questions about their clinical efficacies. And it’s also a top pick despite Lilly’s own bumpy three-years-and-counting path to a hopeful FDA nod.

Donanemab was rejected by the FDA in 2023 due to an insufficient number of patients that were treated with the drug for at least 12 months. Lilly didn’t back down and re-filed several months later in the summer. And now, Lilly is facing yet another setback. In March, the FDA told the company it wants more information about the safety and efficacy of the therapy. This includes the safety results in donanemab-treated patients and the efficacy implications of the “unique trial design of the TRAILBLAZER-ALZ 2 study, including its limited-duration dosing regimen,” according to Lilly. This treatment regimen allowed patients to complete treatment based on an assessment of amyloid plaque and the inclusion of participants based on tau levels.

Biogen’s shelving of Aduhelm and the continuing controversy around Leqembi are expected to impact the fate of donanemab, both pre- and post-approval.

Donanemab faces another challenge in the form of a higher rate of amyloid-related imaging abnormalities (ARIA), a known side effect of beta-amyloid targeting monoclonal antibodies, compared to Leqembi.

It is also entering late into the market. However, despite all of the odds stacked against it, Lilly remains hopeful. In May 2023, Lilly shared data that showed donanemab led to a 35 percent slowing of cognitive decline and a 39 percent lower risk of advancing to the next stage of Alzheimer’s compared to placebo. In comparison, Leqembi led to a 27 percent halting of cognitive decline.


3.   Moderna’s RSV Vaccine

Maker: Moderna

PDUFA: May 12, 2024

Estimated 2028 revenue: $913 million

After GSK won the first ever FDA approval for an RSV vaccine with Arexvy, closely followed by approval of Pfizer’s RSV shot Abrysvo last year, Moderna isn’t too far behind with its RSV vaccine.

Unlike Arexvy and Abrysvo, Moderna’s mRNA-1345 is mRNA-based, and if approved would be the first-in-class mRNA RSV vaccine. Moderna submitted its application for the shot in July last year.

Both Arexvy and Abrysvo are approved for adults 60 years of age and older, with Abrysvo having secured a second approval as a maternal vaccine for the prevention of RSV infection in infants (from birth to six months of age).

Despite Abrysvo’s two approvals, Arexvy took an early market lead last year. In the third quarter of 2023, Arexvy hit almost $900 million in sales and closed in at £1.2 billion ($1.5 billion) for the year. In comparison, Abrysvo only mustered $375 million in third quarter sales, but with an encouraging upward trend, largely due to its maternal indication, and an annual showing of $890 million for the year.

At the J.P. Morgan Healthcare Conference in January, James Mock, chief financial officer at Moderna, said the company is confident it can make a dent in the market due to the vaccine’s efficacy and favorable safety and tolerability.

He also cited the absence of cases of Guillain-Barré syndrome after dosing 37,000 people. The condition is an adverse event linked to competitor vaccines.

With only ten percent of Americans having received an RSV vaccine last year, the market is set for significant growth as uptake increases. Nevertheless, with Arexvy’s early lead, it may be tough for Moderna to play catch up. Despite the world having been introduced to mRNA vaccines through Pfizer and Moderna’s COVID-19 shots, there may still be some lingering hesitancy around mRNA vaccines, despite their high efficacies, that could impact reception to Moderna’s RSV shot.

Moreover, Moderna reported mRNA-1345 to have an efficacy of 84 percent at 3.3 months, which dropped to 63 percent after 8.6 months. In comparison, Arexvy’s efficacy fell from 83 percent to 77 percent at 14 months, while Abrysvo slid from 88.9 percent to 77.8 percent in year two. Experts are concerned that the efficacy of Moderna’s vaccine could have a steeper fall long term at a one year-plus follow-up.

All three companies are evaluating their RSV vaccines in individuals 18 to 59 years of age as well. Pfizer recently shared positive Phase III data from a trial in this age group, which showed the vaccine demonstrated an immune response that was non-inferior to adults 60 years of age and older.


4. Datopotamab deruxtecan for Lung and Breast Cancers

Makers: Daiichi Sankyo/AstraZeneca

PDUFA: Last quarter of 2024 for lung cancer; first quarter of 2025 for breast cancer

Estimated 2028 revenue: $1.8 billion

In February, the FDA accepted the BLA for AstraZeneca and Daiichi Sankyo’s jointly developed datopotamab deruxtecan (Dato-DXd) for the treatment of non-squamous non-small cell lung cancer (NSCLC), setting a PDUFA for the last quarter of 2024.

The companies followed it up with a second BLA submission in patients with HR+, HER2– breast cancer that has been previously treated with systemic therapy. The PDUFA target action date for the breast cancer submission has been set for the first quarter of 2025.

Since the BLA submissions, AstraZeneca and Daiichi shared new trial data that shows the antibody-drug conjugate (ADC) increased progression-free survival in HR+, HER2-low or HER2– breast cancer. The drug will be competing with Gilead’s Trodelvy (sacituzumab govitecan) in this disease subset.

Datopotamab deruxtecan is a TROP2-directed ADC, a next-gen ADC from the same production house that made Enhertu (trastuzumab deruxtecan). Enhertu, approved in certain breast and lung cancers, saw a doubling of total worldwide sales from $1.23 billion in 2022 to almost

While Evaluate predicts Dato-DXd sales to reach $1.8 billion by 2028 if launched this year, despite being second-gen to Enhertu, it isn’t anticipated to overtake the first-gen ADC.

According to GlobalData, Daiichi and AstraZeneca will lead in the ADC space, with revenues predicted to tip over $10 billion by 2029. Other ADC players in oncology include Seagen and Roche, which are estimated to pull in $5.8 billion and $3.6 billion, respectively, from their ADCs by the same year.


5. Heart Drug Acoramidis

Maker: BridgeBio Pharma

PDUFA: November 29, 2024

Estimated 2028 revenue: $1 billion

Acoramidis is a next-generation, highly potent, oral, small molecule transthyretin (TTR) stabilizer that the FDA is reviewing for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM). The FDA accepted BridgeBio’s NDA for the drug in February with a PDUFA of November 29, 2024.

ATTR-CM is a rare, progressive and fatal condition that leads to heart failure and high rates of fatality within four years from diagnosis. Both hereditary and non-hereditary (wild type) forms of the disease are caused by mutations in the TTR gene, which leads to the buildup of TTR protein as fibrils in tissues, such as the peripheral nerves and heart, gastrointestinal system, eyes, kidneys, central nervous system, thyroid and bone marrow. The toxic accumulation of TTR fibrils interferes with the normal functions of these tissues. As tissue damage increases and the disease worsens, quality of life worsens with eventual death.

Worldwide, there are an estimated 300,000 to 500,000 patients with ATTR-CM with many of patients remaining undiagnosed.

Latest Phase III data for the treatment showed that it led to a 30 percent reduction in cardiovascular-related death and hospitalization compared to placebo. Patients who took acoramidis had a 81 percent survival rate compared with 74 percent among patients who received placebo.

BridgeBio will be going up against Pfizer in the heart disease market and while a major uphill battle, analysts think it can capture a sizeable chunk of the market and make some good sales.

Alexion, AstraZeneca Rare Disease is serving as a licensing partner of BridgeBio’s affiliate, Eidos Therapeutics, Inc., to develop and commercialize acoramidis in Japan. Alexion is conducting the Phase III open-label trial in Japan.

Pfizer’s ATTR-CM medication tafamidis, sold under the brand names Vyndaqel and Vyndamax, will likely hold two-thirds of the market in the next several years, according to analysts.

Nevertheless, the ATTR-CM market is posited to experience rapid growth, which will allow space for other players to profit. Sales of tafamidis increased 34 percent to $2.4 billion over the first nine months of 2023.

Commenting at the J.P. Morgan Healthcare Conference in January, BridgeBio CEO Neil Kumar was confident about acoramidis’ faring in the market. He said he “pretty reliably” looks at a 25 percent to 40 percent stake for acoramidis. He believes the drug is “far and away the best reducer of toxic monomer.” He also believes the company can “commercialize effectively” because they know where the prescribers are across the 36,000 cardiovascular practices, of which approximately 1,100 heart failure specialty clinics and around “100 centers of excellence” are “driving growth of the market,” he said.

If you want your company to be featured on Xtalks.com, please email [email protected].