Are small-molecule drugs having their big moment?

With a global market size estimated at $1.64 trillion, pharmaceuticals are a massive business built on miniscule molecules.

And when it comes to those molecules, smaller is increasingly seen as preferable.

Small-molecule drugs—that is, chemically synthesized drugs with a molecular weight under 1,000 daltons—represent a growing portion of treatments being developed across the industry and approved by the Food and Drug Administration (FDA).

Biopharmaceuticals, or biologics, are the newer drug class, more molecularly complex and more heavily funded than their older, smaller sibling. But the small-molecule drug has several advantages over the biologic that could be driving a resurgence in recent years.

Let’s dig into the trends, then take a look at what’s behind them.

Despite gains from biologics, small molecules lead FDA approvals

From 2012 to 2022, small-molecule drugs made up around 57% of new FDA approvals overall. While biologics’ year-to-year performance varied considerably, ranging from 20% in 2013 to 50% in 2022, they still saw a relative gain in share across that period.

But recent years have shown a stronger preference for the compact compounds. In 2024, small-molecule therapies made up 27 of the 50 novel drugs (62%) approved by the FDA. And of the 25 drugs approved by the FDA in 2025 so far, 18 (or 72%) are small-molecule drugs.

These are some of the most noteworthy small-molecule drugs to receive FDA approval this summer:

• Brensocatib (marketed as Brinsupri), the first oral treatment for non-cystic fibrosis bronchiectasis
• Zongertinib (marketed as Hernexeos), an oral kinase inhibitor developed to treat certain non-squamous non-small cell lung cancers
• Dordaviprone (marketed as Modeyso), an anti-cancer medication for patients with diffuse midline glioma tumors
• Delgocitinib (marketed as Anzupgo), a topical cream that treats chronic eczema in patients who can’t use corticosteroids
• Sebetralstat (marketed as Ekterly), the first oral therapy for hereditary angioedema attacks that result in severe swelling throughout the body

Some major players in the pharmaceuticals space are making big moves around small-molecule development in 2025, too:

• Eli Lily and Superluminal Medicines are partnering in a $1.3 billion collaboration to develop small-molecule therapeutics targeting G protein-coupled receptors (GPCR) that could treat cardiometabolic diseases and obesity.
• The Icahn School of Medicine at Mount Sinai in New York City launched the AI Small Molecule Drug Discovery Center in April, leveraging machine learning and traditional discovery methods to accelerate small-molecule drug development.
• The Merck Group announced they would spend up to $2 billion on small-molecule RNA-targeting drugs in a deal with Massachusetts-based Skyhawk Therapeutics.

So what is it about these little molecules that’s earning attention from developers?

It comes down to efficacy, cost-effectiveness, and technological advancements.

Small-molecule drugs are more versatile and cost-effective than biologics

For most of the history of modern medicine, “medication” meant a small-molecule drug: Aspirin, antihistamines, penicillin, to name a few. They are usually chemically synthesized (but can be obtained from organic sources) and are relatively simple in structure, with applications across a wide range of therapy areas.

Measuring only about 1 nanometer wide, small-molecule drugs can easily penetrate cell membranes and cross the blood-brain barrier. Their light weight and small size makes them suitable for most forms of administration, but they are most often administered orally—the method most preferred by patients, and thus the method most likely to support adherence.

But in the past few decades, biopharmaceuticals derived from living cells have enabled new treatments for conditions ranging from diabetes (insulin) to arthritis (adalimumab) to TMJ (Botox).

Biologics tend to be hundreds of times larger than small-molecule drugs and must therefore be administered through injection. This raises the cost of treatment and can lead to diminishing adherence rates.

The organic molecules from which biologics are derived can be sensitive to light, temperature, and other environmental factors, requiring specialized equipment and training to manufacture and store these medications. These conditions contribute to the expenses associated with the development, delivery, and application of biologics.

Evolving regulations could even the playing field

For pharmaceutical companies, however, biologics do have one considerable earnings advantage: Under current law, biologics are exempt from being identified for Medicare price negotiation for 11 years, while small-molecule drugs are exempt for only seven. (Negotiated prices generally go into effect two years after selection, giving pharma developers freedom from price controls for nine and 13 years, respectively.)

In April 2025, President Trump issued an executive order calling for HHS to equalize the negotiation identification exemption period, setting it to 11 years for both categories. The order refers to the discrepancy between categories as a ‘pill penalty’ that “threatens to distort innovation by pushing investment towards expensive biological products, which are often indicated to treat rarer diseases, and away from small molecule prescription drugs, which are generally cheaper and treat larger patient populations.”

If passed into law, this move could make small-molecule drugs more expensive for patients and public payors—but could also bolster pharmaceutical developers’ revenue streams at a time when funding cuts and slowing approvals are straining budgets.

The right tech at the right time

Several emerging technologies are also contributing to the small molecule’s momentum.

Artificial intelligence (AI) tech like machine learning and deep learning support faster, more accurate discovery of drug-like molecular structures that can be selectively optimized for safety, potency, and bioavailability. Generative AI is in the mix, too, making de novo drug design faster and more affordable.

Similarly, predictive modeling techniques can help developers forecast chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET), a critical model for evaluating drug candidates beyond therapeutic efficacy. Assessing these factors earlier in the development process can help developers avoid costly late-stage failures.

New high-throughput screening methods incorporating technologies like affinity selection mass spectrometry allow millions of compounds to be tested rapidly against disease targets and produce massive amounts of data that can then feed AI models for further study. Paired with advancements in molecular glues and targeted protein degraders, developers can more easily identify and modify cellular machinery to induce novel protein-to-protein interactions that could treat cancers and other rare diseases.

Get the Definitive picture of the small-molecule drug market

The small-molecule drug market is rife with opportunities. Whether you’re a developer or selling into the space, data, analytics, and AI can help you find, engage, and win the business opportunities you’re looking for.

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