10 Years of FDA Approvals: Six Designations, 459 Drugs

Every year, the FDA's Center for Drug Evaluation and Research (CDER) publishes an annual report listing every novel drug it approved that year, along with which regulatory designations each drug received. Novel means the active ingredient has never been approved in the US before.

Designations are labels the FDA assigns to drugs during development and review. They signal how the FDA categorizes a drug's novelty, the urgency of the medical need, and the speed of its review. There are six: first-in-class (new mechanism), orphan drug (rare disease), breakthrough therapy (substantial improvement over existing treatments), accelerated approval (approved on surrogate endpoints), priority review (6-month review instead of 10), and fast track (rolling review for unmet needs).

We analyzed 10 years of these reports, matched every drug to our database, and tagged each one with all six designations. The result is a structured dataset covering a decade of FDA novel drug approvals - 459 drugs, each with a full designation profile.

Here is what a decade of designations reveals.

Half of all new drugs target rare diseases

Of the 459 novel drugs approved from 2016 to 2025, 233 (51%) received orphan drug designation - meaning they target diseases that affect fewer than 200,000 people in the US.

This is the most stable number in the entire dataset. The orphan drug share has never dropped below 36% and has stayed above 50% in seven of the last eight years. It is not a trend. It is the baseline.

These are not obscure conditions. Spinraza (2016) treats spinal muscular atrophy - a genetic disease that destroys motor neurons in infants. Hemlibra (2017) prevents bleeding in hemophilia A patients who developed antibodies against their existing treatment. Evrysdi (2020) became the first oral treatment for SMA, making it accessible to patients who couldn't reach an infusion center. Skyclarys (2023) is the first treatment ever approved for Friedreich's ataxia, a degenerative disease that damages the nervous system and has no cure.

Why does half the pipeline target rare diseases? The Orphan Drug Act of 1983 offers powerful incentives: seven years of market exclusivity, tax credits for clinical trial costs, and waived FDA filing fees. For small biotechs, these incentives can make the difference between a viable program and an abandoned one. The result is that rare disease drug development is not a niche corner of pharma. It is the largest single category of novel drug approvals.

42% of new drugs have genuinely new mechanisms

Of the 459 novel drugs, 192 (42%) were designated first-in-class by the FDA. That means they work through a mechanism of action that no previously approved drug uses.

Some of the most important drugs of the last decade are first-in-class: Tecentriq (2016) was the first PD-L1 checkpoint inhibitor for cancer. Dupixent (2017) introduced IL-4/IL-13 blockade for atopic dermatitis - now a $14B/year drug treating four diseases. Onpattro (2018) was the first RNA interference (RNAi) therapy ever approved - an entirely new modality. Aimovig (2018) was the first CGRP antibody for migraine, creating a drug class that now serves millions. Mounjaro (2022) was the first dual GIP/GLP-1 receptor agonist - now one of the fastest-growing drugs in history.

What first-in-class does not mean: it does not mean the drug is better than existing treatments. A first-in-class drug might be less effective than an established therapy in the same disease. The designation tells you the mechanism is novel, not that the outcome is superior. But the fact that 42% of novel approvals over a decade are genuinely new mechanisms - not me-too drugs - is a measure of real innovation in the pipeline.

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Breakthrough therapy doubled - then held

Breakthrough therapy designation went from 24% in 2018 to 43% in 2020, then settled around 33-36% from 2023 onward. It is the designation with the most movement over the decade.

The FDA grants breakthrough therapy when preliminary clinical evidence shows a drug may offer substantial improvement over existing treatments for a serious condition. It is not just about novelty - the FDA needs to see early data suggesting the drug could meaningfully change outcomes. In return, the company gets intensive FDA guidance during development, rolling review, and senior management involvement.

The drugs that earned this designation are some of the most impactful of the decade. Trikafta (2019) achieved a 90% response rate in cystic fibrosis - transforming a fatal childhood disease into a manageable condition. Dupixent (2017) showed dramatic improvement in severe eczema patients who had failed every other therapy. Enhertu (2019) demonstrated tumor shrinkage in breast cancer patients whose tumors were considered too low in HER2 to treat - rewriting the definition of HER2-positive cancer. Hemlibra (2017) reduced bleeding episodes by 87% in hemophilia patients with inhibitors, an area with very limited options.

Accelerated approval peaked in 2021 - and the Aduhelm effect

In 2021, 27% of novel drugs (13 of 49) were approved via the accelerated approval pathway - the highest rate in our dataset. By 2024, that number had dropped to 14%.

Accelerated approval lets the FDA approve a drug based on a surrogate endpoint - a biomarker or intermediate measure that is "reasonably likely" to predict clinical benefit, rather than requiring proof that the drug actually makes patients live longer or feel better. The trade-off: the company must run confirmatory trials after approval, and the FDA can withdraw the drug if those trials fail.

Some of the most important cancer drugs of the decade came through this pathway. Tecentriq (2016) was approved for bladder cancer based on tumor response rate, then confirmed in later trials. Venclexta (2016) reached CLL patients based on overall response rate. Lumakras (2021) was the first drug to target KRAS G12C - approved on response rate after decades of KRAS being considered undruggable. Trodelvy (2020) reached triple-negative breast cancer patients based on response rate, later confirmed with overall survival data.

But the 2021 spike also included Aduhelm (aducanumab) for Alzheimer's disease - one of the most controversial FDA approvals in recent history. Approved on amyloid plaque reduction (the surrogate) despite an advisory committee voting against it, Aduhelm became a lightning rod for debate about whether the accelerated approval pathway was being stretched too far. CMS ultimately restricted coverage. The rate dropped to 14-16% in 2022-2024 - then rebounded to 24% in 2025 (11 of 46 drugs). The pathway isn't shrinking. After a period of recalibration, the FDA appears to be using it as actively as before, but with drugs where the surrogate endpoints are better validated.

The FDA is getting more predictable

Priority review rates have actually declined over the decade - from 68% in 2016 to 46% in 2025. This does not mean fewer drugs are important. It means more drugs are using the standard 10-month review timeline and still getting approved on schedule.

The FDA met its PDUFA goal dates for 100% of novel drugs in 2017 and 2018, and has stayed above 89% every year since. For companies planning a drug launch, this predictability is enormously valuable. If the FDA gives you a PDUFA date, you can book your sales force, line up your supply chain, and brief your investors with high confidence that the decision will come on time.

All six designations, side by side

What the heatmap shows: orphan drug and priority review are consistently the darkest columns - rare disease and expedited review are the FDA's default mode for novel drugs, not the exception. Accelerated approval stays light - it remains a selective pathway even after 2025's rebound. And first-in-class holds steady in the middle, showing that roughly four in ten novel drugs bring a genuinely new mechanism to patients every year.

Once you know what each designation signals, you read every FDA approval differently. Orphan drug tells you the economics worked because of the Orphan Drug Act. First-in-class tells you the science is genuinely new. Breakthrough therapy tells you the FDA saw something remarkable in the early data. Accelerated approval tells you the unmet need was urgent enough to accept a surrogate endpoint. Priority review tells you the agency moved fast.

459 drugs. Ten years. The data is now searchable, filterable, and explorable.