In 2024, FDA Approved Innovative Treatments for Several Complex Diseases

Reprinted with AIS Health permission from the December 2024 issue of Radar on Specialty Pharmacy

While the FDA’s 44 novel drug approvals as of Dec. 11 may have been lower than 2023’s 55, the agency still green-lighted some impressive agents. Among those were the first agent for a liver disease that can have serious complications; the most expensive gene therapy ever, which was approved for a disease that shortens lifespans, particularly among children; and a first-in-class therapy for a solid tumor. The agency also granted additional indications to already-available treatments, including several chimeric antigen receptor T cell (CAR-T) therapies. Industry experts spoke with AIS Health about some of the top FDA approvals of 2024. (Editor’s note: These comments have been edited for length and clarity.)

AIS Health: What were the most important FDA specialty drug approvals in 2024 and why?

Renee Rayburg, R.Ph., vice president of specialty clinical consulting at Pharmaceutical Strategies Group (PSG), an EPIC company: To date, as of Dec. 9, there have been 44 novel drug approvals in the U.S. through the Center for Drug Evaluation and Research (CDER) of the FDA. These are new drugs that have never before been FDA-approved or marketed in the U.S. Of those, 70% (31) are specialty drugs, and 27% (12) are oncology drugs. As a comparison, there were 55 novel drug approvals in 2023. Some notable approvals include:

The first FDA-approved drug for the treatment of non-alcoholic steatohepatitis (NASH) /metabolic-dysfunction associated steatohepatitis (MASH), Rezdiffra [(resmetirom)]. Despite being the first and only FDA-approved drug for NASH, Rezdiffra, an oral medication manufactured by Madrigal Pharmaceuticals, initially had a slow uptake but outperformed expectations in [the third quarter]. Annual costs are estimated around $47,400 per patient. Weight-loss GLP-1s semaglutide and tirzepatide are also being studied for NASH with some positive results. Manufacturers are considering submission for NASH as an expanded indication, which may create some competition in the market, as the annual costs of GLP-1s are much lower than Rezdiffra. It is not clear exactly how these drugs will be used if approved, but future treatments for NASH seem promising.
The most expensive drug ever FDA-approved, Lenmeldy [(atidarsagene autotemcel) from Kyowa Kirin division Orchard Therapeutics plc], was approved in March at a list price of $4.25 million. This one-time treatment gene therapy is indicated for children with metachromatic leukodystrophy (MLD), an ultra-rare progressive genetic disease that affects the brain and nervous system. It is estimated that 40 to 100 babies are born with MLD in the U.S. each year, and it has an estimated mortality rate of 50% at 5 years for patients with late infantile disease and 44% at 10 years for those with juvenile disease.
The FDA fully approved Kisunla [(donanemab-azbt) from Lilly], making it the second disease-modifying anti-amyloid therapy to receive full FDA approval for the treatment of Alzheimer’s disease [after Eisai Inc. and Biogen’s Leqembi (lecanemab-irmb)]. It’s estimated these drugs slow disease progression by about 30%, but the drugs do have side effects that need to be considered. CMS does offer full coverage of these two drugs with utilization management.

Andy Szczotka, Pharm.D., chief pharmacy officer at AscellaHealth: Some notable approvals include:

Rezdiffra: Two types of nonalcoholic fatty liver disease (NAFLD) are nonalcoholic fatty liver (NAFL) and NASH. NAFLD is the most common chronic liver disease in the U.S., affecting roughly 25% of adults. Twenty percent of people with NAFLD develop NASH, with it being most common among people who are obese and/or have Type 2 diabetes. As these conditions become more prevalent, so does NASH.
Miplyffa (arimoclomol) [from Zevra Therapeutics, Inc.] and Aqneursa (levacetylleucine) [from IntraBio Inc.]: Prior to the approval of these agents in November, miglustat was the only available treatment option for Niemann-Pick disease type C (NPC). Both agents were approved for the treatment of neurological manifestations of NPC in adult and pediatric patients. Miplyffa is indicated for use in combination with miglustat in patients 2 years of age and older while Aqneursa is indicated for patients weighing at least 15 kg, without the requirement for miglustat. NPC is an ultra-rare progressive neurodegenerative disease caused by autosomal recessive mutations in the NPC1 or NPC2 genes that lead to premature death, with most individuals dying between 10 and 25 years of age. NPC can present at any age and many individuals with NPC may be misdiagnosed or undiagnosed. The estimated prevalence of NPC is approximately 2.9 per million lives.
Duvyzat (givinostat) [from Italfarmaco S.p.A. unit ITF Therapeutics LLC]: Duvyzat is the first oral treatment approved for Duchenne muscular dystrophy (DMD) to offer a novel mechanism of action of histone deacetylase inhibition. Duvyzat is the first nonsteroidal drug approved to treat patients with all genetic variants of DMD in patients 6 years of age and older. The inhibition of histone deacetylase may activate repair mechanisms that can prevent muscle degeneration and reduce inflammation.
Kisunla: Kisunla is approved for adults with early symptomatic Alzheimer's disease. It is administered as a once-monthly IV infusion and competes with Leqembi. Kisunla is the only approved amyloid plaque targeting therapy that uses a limited-duration treatment regimen based on amyloid plaque removal. The label for Kisunla includes a Boxed Warning regarding amyloid-related imaging abnormalities (ARIA), which is similar to Leqembi.
Winrevair (sotatercept-csrk) [from Merck & Co., Inc.]: Winrevair is the first treatment for pulmonary arterial hypertension that works through a mechanism of action that does not involve vasodilation and is the first treatment that may be disease-modifying by potentially halting or reversing PAH progression, but long-term studies will be needed to verify this.
Hympavzi (marstacimab-hncq) [from Pfizer Inc.]: Hympavzi is the first and only anti-tissue factor pathway inhibitor, which is a novel approach to hemophilia management, in the U.S. It can be given to patients once a week.
Beqvez (fidanacogene elaparvovec) [from Pfizer]: Beqvez, an adeno-associated virus (AAV) vector-based gene therapy, is indicated for the treatment of hemophilia B in adults. It is a one-time gene therapy for hemophilia B that contains a high-activity variant of human coagulation factor IX gene. It competes with Hemgenix, the other available gene therapy for hemophilia B.

Mesfin Tegenu, R.Ph., CEO and chairman of RxParadigm, Inc.: The FDA approved several specialty drugs in 2024, with notable approvals including Amtagvi [(lifileucel) from Iovance Biotherapeutics, Inc.], Hympavzi, Rezdiffra and Yorvipath [(palopegteriparatide) from Ascendis Pharma A/S]. Amtagvi is a one-time tumor-infiltrating lymphocyte (TIL) therapy for advanced melanoma, marking the first one-time cell therapy approved for treating a solid tumor. Hympavzi is the first anti-tissue factor pathway inhibitor approved for both hemophilia A and B and the first hemophilia medication administered using a prefilled, autoinjector pen. It is also the first nonfactor, subcutaneous prophylactic treatment for hemophilia B. Rezdiffra is the first FDA-approved treatment for NASH, also known as MASH. NASH is a liver disease with significant unmet needs, often leading to serious liver complications and becoming one of the leading causes of liver transplantation. Yorvipath is the first and only medication approved for hypoparathyroidism in adults. Yorvipath is a prodrug formulation of parathyroid that specifically targets the underlying cause of hypoparathyroidism. These approvals mark notable advancements in treating complex diseases with unmet needs.

AIS Health: What have been the most significant occurrences within oncology in 2024?

Rayburg: Science continues to advance in oncology with new drug approvals, expanded indications and improved dosage forms being studied to enhance the patient experience. Much of the focus is on immunotherapy, studying how these drugs can stimulate the body’s own immune cells to help fight the cancers. In addition, most of the therapies are very targeted to specific genetic mutations to match the right drugs to the right patients in terms of genetic makeup to achieve optimal benefit. Some of the advancements in 2024 have led to approvals for earlier use of some therapies, lessening some of the previous use requirements or trial/failure of treatments before use and moving the oncology drugs up to first-line use for some indications. In addition, one FDA approval stands out as it is the first cell therapy FDA-approved for solid tumors; Amtagvi is FDA-approved for the treatment of aggressive forms of melanoma using immune cells from the tumor. Breyanzi [(lisocabtagene maraleucel) from Juno Therapeutics, Inc., a Bristol Myers Squibb company] is also the first CAR-T cell therapy FDA-approved for the treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

Szczotka: Approximately one-quarter of the FDA novel drug approvals in 2024 were for oncology-related products. In addition to those approvals, additional cell therapies were approved for oncology in 2024. Some notable approvals and expanded labels in 2024 include:

Keytruda (pembrolizumab) [from Merck] is a human (programmed death receptor-1 [PD-1]) blocking antibody and has seen its FDA approved indications grow to 21 types of cancer. Used as an immunotherapy, it gained an additional three indications in 2024.
Opdivo (nivolumab) [from Bristol Myers Squibb] is a PD-1 blocking antibody and, similar to Keytruda, has seen its FDA-approved indications grow in 2024. Opdivo added two new indications in 2024, bringing its approved use to 11 types of cancer.
Kisqali (ribociclib) [from Novartis Pharmaceuticals Corp.] was approved with an aromatase inhibitor for the adjuvant treatment of adults with hormone receptor positive, human epidermal growth factor receptor 2 (HER2) negative stage II and III early breast cancer at high risk of recurrence. Additionally, the FDA also approved the combination product Kisqali Femara Co-Pack for the same indication.
Itovebi (inavolisib) [from Roche Group member Genentech USA., Inc.] was granted priority review and breakthrough designation and approved with palbociclib and fulvestrant for adults with endocrine-resistant, PIK3CA-mutated, hormone receptor positive, HER2 negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy.

For the CAR-T therapies:

Breyanzi gained additional FDA accelerated approval for the treatment of adult patients with relapsed or refractory follicular lymphoma who have received two or more prior lines of systemic therapy, as well as for relapsed or refractory CLL or SLL.
Carvykti (ciltacabtagene autoleucel) [from Legend Biotech USA, Inc. and Johnson & Johnson] gained an expansion for its indication to include treatment of adults with relapsed or refractory multiple myeloma who have received at least one prior line of therapy, moving it into an earlier line of treatment.
Abecma (idecabtagene vicleucel) [from Bristol Myers Squibb and 2seventy bio] gained an improved label for use in relapsed or refractory multiple myeloma after two or more prior lines of therapy, making it available in earlier lines of treatment to patients who have relapsed or become refractory.
Tecelra (afamitresgene autoleucel) was approved for the treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy. This was the first agent FDA approved for this use since Votrient [(pazopanib) from Novartis] in 2012.
Amtagvi became the first TIL therapy approved by the FDA for the treatment of unresectable or metastatic melanoma. This involves isolating and expanding T cells from the tumor, then reintroducing them to the body to attack cancer cells.

Tegenu: The growth of the oncology market, particularly with the advancements in antibody-drug conjugates (ADCs) and CAR-T cell therapies, was significant in oncology this past year. ADCs are expanding beyond hematologic cancers to include solid tumors such as lung and gastrointestinal cancers. According IQVIA’s Global Oncology Trends 2024 Report, ADC development in solid tumors has experienced an 80% growth over the past two years. Unlike conventional chemotherapies, which often lack specificity and show modest therapeutic effects, ADCs offer targeted treatments with reduced toxicity. This precision-targeted approach delivers cytotoxic agents directly to cancer cells while reducing systemic side effects associated with traditional treatments. ADCs are increasingly being used in combination therapies, including use as first-line treatment options in oncology.

Similarly, CAR-T cell therapies, previously limited to hematologic malignancies, are now advancing into solid tumors like gastric and pancreatic cancers. These therapies provide a highly targeted, personalized approach by reprogramming a patient’s T cells to specifically recognize and attack cancer cells, in contrast to conventional therapies, which can affect both healthy and malignant cells. IQVIA’s report mentions that clinical trials for CAR-T cell therapies targeting solid tumors have nearly doubled over the last five years, reflecting growing demand and confidence in their potential. The growth of the oncology market reflects a shift toward more personalized and innovative cancer care approaches, focused on improving outcomes and expanding treatment options for patients with complex cancers.

By Angela Maas