FDA approves second highest number of novel therapies in 30 years!

The FDA greenlit 55 new drugs in 2023, an impressive surge of nearly 50% compared to the previous year. This included a substantial uptick in both small molecules and biologics, and featured several groundbreaking first-in-class or disease-specific approvals. The drug approval landscape witnessed notable strides being made across major therapeutic areas, orphan diseases, and emerging modalities. This overview reflects on the noteworthy developments and key highlights of 2023. But we'll also explore potential trends and pivotal events to anticipate in the dynamic landscape of drug approvals, as we look ahead at 2024.

30 Years of New Approvals by the FDA

Excludes vaccines and gene therapies. Adapted from Muller A, 2023 FDA approvals, Nature Reviews in Drug Discovery, Jan 2024.

Oncology maintains its lead by securing the highest number of approvals.

In 2023, the FDA granted approval to 13 new cancer therapies, accounting for 24% of all approvals. Neurology followed closely with nine approvals, representing 16% of the total, while Infectious diseases and haematology shared the third position with five approvals each (both contributing 9% each of total approvals).

FDA Approvals by Therapeutic Area

Adapted from Muller A, 2023 FDA approvals Nature Reviews in Drug Discovery, Jan 2024.

By modality, the diversity of the medical toolbox continues to expand.

2023 saw an increase in approvals of nucleotide-based therapeutics, including a second RNA-aptamer drug, as well as four T cell bispecific antibodies, capable of simultaneously binding a cancer antigen and a T cell.

Adapted from Muller A, 2023 FDA approvals Nature Reviews in Drug Discovery, Jan 2024.

Here, FDA approvals are displayed by modality: including small molecules, or peptides of up to 40 amino acids in length, and oligonucleotides, which are approved as New Molecular Entities. Protein-based candidates are approved through biologics licence applications, including mAbs (monoclonal antibodies) and siRNA (small interfering RNA).

Orphan Drugs

In the realm of orphan drugs, which target indications affecting fewer than 200,000 people, pharmaceutical developers continue to capitalise on the reduced market competition and relatively favourable regulatory environments associated with addressing 'orphan diseases.' Notably, 52% of total approvals in 2023 were granted in this domain.

Firsts in 2023

Cancer discovery saw a number of first in class approvals. For example, AstraZeneca's capivasertib (Truqap) achieved a significant milestone in becoming the first AKT inhibitor approved – in this case when used in combination with the estrogen receptor antagonist fulvestrant for hormone-receptor-positive, HER2-negative metastatic breast cancer exhibiting biomarker alterations in PIK3CA, AKT1, or PTEN. AKT is a key component of the PI3K–AKT–mTOR signaling pathway, and while inhibitors targeting PI3K and mTOR have previously gained approval, capivasertib represents a novel approach. The drug's approval is also accompanied by a companion diagnostic tool that assesses the status of PIK3CA, AKT1, and PTEN. This diagnostic aids in identifying patients most likely to respond to the treatment, narrowing the number of patients that would receive the treatment by approximately half.

The FDA's approval of Astellas’ fezolinetant (Veozah) to alleviate hot flushes associated with menopause also represents a significant step forward - especially considering that a substantial number of menopausal women either cannot undergo the standard hormone therapy recommended for managing this condition, or opt not to receive it. By targeting the neurokinin 3 receptor, fezolinetant offers an alternative and effective approach for addressing this prevalent menopausal symptom.

Approvals to watch out for in 2024

Expect significant additions to the pharmacopeia and some standout new entrants in 2024. For example, the non-profit Multidisciplinary Association for Psychedelic Studies (MAPS) organisation is aiming to secure approval for the use of MDMA in treating post-traumatic stress disorder (PTSD) - setting a precedent for the broader application of hallucinogens in various psychiatric indications.

Meanwhile, Eli Lilly’s Alzheimer’s targeting monoclonal antibody donanemab was denied accelerated approval in January 2022, but could be soon approved on the basis of the phase III Trailblazer-ALZ 2 trial, which showed a significant benefit for the mAb over placebo in Alzheimer’s patients over 18 months.

Adapted from Muller A, FDA approvals, Nature Reviews in Drug Discovery, Jan 2024.