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Investigational Drug Information for Darapladib
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What is the development status for investigational drug Darapladib?
Darapladib is an investigational drug.
There have been 19 clinical trials for Darapladib.
The most recent clinical trial was a Phase 3 trial, which was initiated on December 1st 2008.
The most common disease conditions in clinical trials are Atherosclerosis, Myocardial Ischemia, and Coronary Artery Disease. The leading clinical trial sponsors are GlaxoSmithKline, The TIMI Study Group, and National Heart, Lung, and Blood Institute (NHLBI).
Summary for Darapladib
| US Patents | 0 |
| International Patents | 0 |
| US Patent Applications | 421 |
| WIPO Patent Applications | 135 |
| Japanese Patent Applications | 7 |
| Clinical Trial Progress | Phase 3 (2008-12-01) |
| Vendors | 58 |
Recent Clinical Trials for Darapladib
| Title | Sponsor | Phase |
|---|---|---|
| Effect of Darapladib on Cantharidin-Induced Inflammatory Blisters in Subjects With Type 2 Diabetes Mellitus (T2DM) | GlaxoSmithKline | Phase 1 |
| Darapladib China PK | GlaxoSmithKline | Phase 1 |
| Pharmacokinetic Interaction of Darapladib and CYP 3A4 in Healthy Subjects | GlaxoSmithKline | Phase 1 |
Clinical Trial Summary for Darapladib
Top disease conditions for Darapladib
Top clinical trial sponsors for Darapladib
US Patents for Darapladib
| Drugname | Patent Number | Patent Title | Patent Assignee | Estimated Expiration |
|---|---|---|---|---|
| >Drugname | >Patent Number | >Patent Title | >Patent Assignee | >Estimated Expiration |
Darapladib Development Update, Patent Position, and Market Projection
Darapladib is a discontinued cardiovascular drug candidate that selectively inhibits lipoprotein-associated phospholipase A2, or Lp-PLA2. GlaxoSmithKline tested it in two large Phase III programs for secondary prevention in patients with coronary artery disease and acute coronary syndrome. Both programs failed their primary efficacy objectives. Darapladib has no FDA approval, no Orange Book listing, no established commercial revenue, and no active branded market as of 2025. Its realistic current market projection is zero unless another sponsor restarts development with a new clinical strategy.
What is darapladib and how does it work?
Darapladib, also known as SB-480848, is an oral small-molecule inhibitor of Lp-PLA2. The enzyme is associated with LDL particles and is expressed in atherosclerotic plaque. The development hypothesis was that reducing Lp-PLA2 activity would limit production of pro-inflammatory lipid mediators and reduce plaque-related cardiovascular events.
The candidate was developed primarily for:
- Coronary artery disease
- Atherosclerotic cardiovascular disease
- Acute coronary syndrome
- Secondary prevention of myocardial infarction and ischemic stroke
Darapladib was intended to complement, rather than replace, standard therapy such as statins, antiplatelet agents, beta blockers, and renin-angiotensin system inhibitors.
The mechanism generated strong biological interest because high Lp-PLA2 levels correlate with cardiovascular risk. The Phase III results showed that epidemiological association did not translate into a clinically effective treatment strategy.
What happened in the darapladib Phase III development program?
Darapladib failed two major Phase III cardiovascular outcomes trials.
| Trial | Population | Enrollment | Primary endpoint | Result |
|---|---|---|---|---|
| STABILITY | Stable coronary artery disease | 15,828 | Major cardiovascular events | Failed |
| SOLID-TIMI 52 | Recent acute coronary syndrome | 13,026 | Cardiovascular death, myocardial infarction, or urgent coronary revascularization | Failed |
What did the STABILITY trial show?
The STABILITY trial evaluated darapladib in patients with stable coronary artery disease. The study randomized 15,828 patients to darapladib or placebo on top of standard cardiovascular treatment.
Darapladib did not significantly reduce the primary composite endpoint of cardiovascular death, myocardial infarction, or stroke. The hazard ratio was approximately 1.00, indicating no meaningful treatment effect. The trial also reported adverse effects that affected tolerability, including diarrhea, nausea, and an odor-related effect associated with the compound.
The results were published in the New England Journal of Medicine in 2014 (White et al., 2014).
What did the SOLID-TIMI 52 trial show?
SOLID-TIMI 52 evaluated darapladib in 13,026 patients after an acute coronary syndrome event. Patients received darapladib or placebo in addition to contemporary standard care.
The primary endpoint was cardiovascular death, myocardial infarction, or urgent coronary revascularization. Darapladib did not reduce the endpoint. The hazard ratio was approximately 1.00, with no statistically significant efficacy signal.
The results were published in JAMA in 2014 (O'Donoghue et al., 2014).
When did darapladib lose its development opportunity?
Darapladib's commercial development opportunity effectively ended after the negative STABILITY and SOLID-TIMI 52 outcomes.
Darapladib development timeline
| Year | Event |
|---|---|
| Early 2000s | Lp-PLA2 inhibition program developed by GlaxoSmithKline and predecessor organizations |
| 2008-2012 | Phase II studies evaluated biomarker effects, safety, and vascular outcomes |
| 2013 | STABILITY completed and reported no primary endpoint benefit |
| 2014 | SOLID-TIMI 52 completed and reported no primary endpoint benefit |
| 2014-2015 | Cardiovascular development program was discontinued |
| 2016 onward | No meaningful clinical development or regulatory progression |
| 2025 | No approval, no commercial product, and no active late-stage program |
The failure was not caused by a marginal statistical miss. Both large outcome trials failed to demonstrate a clinically relevant reduction in cardiovascular events. That result sharply reduced the probability of a conventional resubmission or an approval based on the existing dataset.
What is the FDA regulatory status of darapladib?
Darapladib is not FDA approved.
The candidate has no New Drug Application approval, no FDA-approved indication, and no approved dosage form. It is not listed in the FDA Orange Book as an approved drug product. It therefore has no FDA statutory exclusivity period, no approved-label market protection, and no authorized generic or branded commercial market.
| Regulatory category | Darapladib status |
|---|---|
| FDA approval | None |
| Approved indication | None |
| Orange Book listing | None |
| New Chemical Entity exclusivity | Not granted because no approval occurred |
| Pediatric exclusivity | None |
| Orphan-drug exclusivity | None identified |
| Authorized generic | None |
| Biosimilar pathway | Not applicable |
The absence of approval is more important than any remaining patent term. A competitor would not need to wait for FDA regulatory exclusivity to expire because darapladib never obtained an approved product designation.
What patents protect darapladib?
Darapladib was covered by a historical patent estate directed to the compound, pharmaceutical compositions, Lp-PLA2 inhibition, and therapeutic use. The estate was associated principally with GlaxoSmithKline and predecessor entities.
The relevant protection likely included several patent families:
- Compound patents covering darapladib and related heterocyclic inhibitors.
- Composition patents covering pharmaceutical formulations and solid dosage forms.
- Method-of-use patents covering treatment or prevention of atherosclerotic and inflammatory cardiovascular disease.
- Manufacturing and intermediate patents covering chemical synthesis routes.
- International applications and national-phase rights in the United States, Europe, Japan, and other major pharmaceutical markets.
A precise live-claim assessment cannot be inferred from the clinical program alone. Patent term, terminal disclaimers, patent-term adjustment, maintenance fees, continuations, national validation, and claim scope must be evaluated family by family.
Is the darapladib patent estate commercially important?
The estate has limited commercial value in its current form for three reasons:
- Darapladib has no approved indication.
- The two principal cardiovascular outcome trials were negative.
- Any remaining composition or method claims would face substantial validity, enablement, obviousness, written-description, and clinical-utility challenges if asserted against a new development program.
Patent protection could still matter in a revival scenario if a sponsor identified a new disease setting, biomarker-selected population, formulation, or combination regimen. That use would require new clinical evidence and would not restore the failed broad cardiovascular opportunity automatically.
Are there Paragraph IV challenges or darapladib patent litigation?
No material Paragraph IV litigation or active generic-launch dispute is associated with darapladib as of 2025.
Paragraph IV litigation generally requires an approved reference-listed drug or an Abbreviated New Drug Application directed to a listed product. Darapladib has no Orange Book-listed reference product. That removes the standard Hatch-Waxman pathway for a conventional generic challenge.
No major commercial patent settlement is publicly associated with darapladib. The principal risk event was clinical failure, not a generic challenge or patent invalidity judgment.
What formulations are protected by darapladib patents?
The clinical program used oral darapladib formulations, generally administered as tablets. Historical patent protection would be expected to cover some combination of:
- Oral solid dosage forms
- Pharmaceutical compositions containing darapladib
- Excipients and stability systems
- Dose regimens
- Salt, polymorph, or solid-state forms, if separately claimed
- Manufacturing processes and intermediates
The formulation estate does not create a practical market barrier without an approved product. A formulation patent cannot generate commercial exclusivity where the underlying product has failed clinical development and has no FDA-approved label.
How strong is the darapladib patent estate?
The patent estate is weak as a standalone commercial asset and potentially stronger only as a component of a successful new clinical program.
| Asset characteristic | Assessment |
|---|---|
| Composition-of-matter value | Historically important, but likely aged and subject to term erosion |
| Regulatory exclusivity | None |
| Orange Book leverage | None |
| Method-of-use value | Low for the failed broad cardiovascular indications |
| Formulation value | Limited without approval or differentiated clinical performance |
| Manufacturing value | Potentially relevant to cost and supply, but unlikely to block independent development |
| Litigation leverage | Low |
| Repurposing value | Possible but unproven |
| Overall commercial strength | Low |
The central weakness is not simply patent age. It is the absence of evidence that Lp-PLA2 inhibition improves clinical outcomes in the populations tested.
What is the current market projection for darapladib?
Darapladib has no current market revenue because it is not approved or marketed.
Base-case market projection
| Period | Projected commercial status | Revenue outlook |
|---|---|---|
| 2025-2027 | No approved product; no active late-stage program | Approximately $0 |
| 2028-2030 | No market entry without a new sponsor and new trials | Approximately $0 |
| Beyond 2030 | Low probability of commercial revival | Highly speculative |
A conventional commercial forecast should not assign meaningful sales to darapladib. A drug cannot reach a cardiovascular market without demonstrating event reduction, obtaining regulatory approval, and establishing a differentiated position against low-cost generic standards of care.
What would be required for a revival?
A credible revival would require:
- A new target-population rationale
- A biomarker strategy that identifies patients more likely to respond
- New Phase II evidence tied to clinical outcomes or validated surrogate measures
- A clear safety and tolerability solution
- A new sponsor willing to fund a large cardiovascular outcomes program
- Patent or regulatory protection sufficient to justify development cost
The probability-adjusted value of such a program would remain low unless new biology materially changed the interpretation of the earlier trials.
How does darapladib compare with competing cardiovascular drugs?
Darapladib has no competitive commercial position against established cardiovascular therapies.
| Therapy class | Representative products | Clinical role | Darapladib comparison |
|---|---|---|---|
| Statins | Atorvastatin, rosuvastatin | LDL reduction and event prevention | Darapladib did not displace statin therapy |
| PCSK9 inhibitors | Evolocumab, alirocumab | Additional LDL reduction | Stronger outcomes evidence and approved use |
| Antiplatelet agents | Clopidogrel, ticagrelor | Prevention after acute coronary syndrome | Established benefit in defined populations |
| SGLT2 inhibitors | Dapagliflozin, empagliflozin | Cardiovascular and renal risk reduction | Broad approved indications |
| GLP-1 receptor agonists | Semaglutide and others | Metabolic and cardiovascular risk reduction | Active commercial market with outcomes data |
| Lp-PLA2 inhibition | Darapladib | Investigational | No demonstrated event reduction |
Darapladib also does not compete with biologics in the biosimilar sense. It is a small molecule, so biosimilar regulation is not applicable. Any future follow-on product would be treated as a generic or new drug product, depending on the regulatory pathway and whether an approved reference product existed.
What licensing deals and ownership issues affect darapladib?
GlaxoSmithKline controlled the major clinical development program. Publicly disclosed information does not indicate a current commercial license supporting an active darapladib development program.
The asset may retain residual value as:
- A research tool for Lp-PLA2 biology
- A chemical starting point for next-generation inhibitors
- A potential repurposing candidate
- A source of historical clinical and biomarker data
The negative Phase III trials reduce the value of an outright asset acquisition. A transaction would more likely be structured as an option, low upfront license, or research collaboration than as a conventional late-stage pharmaceutical license.
What generic launch scenarios exist for darapladib?
There is no near-term generic launch scenario because there is no approved reference product.
Three scenarios are possible in theory:
Scenario 1: No further development
This is the base case. The program remains discontinued, no NDA is filed, and commercial revenue remains zero.
Scenario 2: Sponsor-led repurposing
A sponsor could develop darapladib for a narrower population or different inflammatory disease. This would require new clinical trials and new intellectual-property positioning. The probability of success is low based on the cardiovascular outcomes record.
Scenario 3: New chemical entity derived from the program
A company could use darapladib data to develop a more selective or better-tolerated Lp-PLA2 inhibitor. That would be a new product opportunity, not a direct darapladib launch. New composition-of-matter protection could be available, but the failed target-validation history would remain a material investment risk.
What geographic coverage remains relevant?
Historical patent filings likely covered the United States, Europe, Japan, and other major pharmaceutical markets. The practical value of those rights depends on individual national status and expiry.
Geographic patent coverage does not create a global barrier because:
- Patent terms may have expired or be close to expiry.
- Some rights may have lapsed for nonpayment.
- Method claims may be difficult to enforce without an approved use.
- No country has an approved darapladib product supporting commercial exclusivity.
The United States remains the most important jurisdiction for any revival because of market size, FDA requirements, and patent litigation exposure. Europe and Japan would require separate regulatory and patent strategies.
Key Takeaways
- Darapladib is an oral Lp-PLA2 inhibitor developed by GlaxoSmithKline.
- The STABILITY trial in 15,828 patients failed to reduce major cardiovascular events.
- The SOLID-TIMI 52 trial in 13,026 patients also failed its primary endpoint.
- Darapladib is not FDA approved and has no Orange Book listing.
- No FDA exclusivity, biosimilar pathway, Paragraph IV dispute, or commercial generic challenge exists.
- Historical compound, formulation, method-of-use, and manufacturing patents may exist, but they have limited current commercial leverage.
- Darapladib has no current market revenue.
- The base-case 2025-2030 market projection is approximately zero.
- Any value would depend on a new indication, new clinical evidence, and a new sponsor.
- The asset is better characterized as a discontinued research program than as a near-commercial cardiovascular product.
FAQs About Darapladib Development and Commercial Potential
Why did darapladib fail despite Lp-PLA2 being associated with cardiovascular risk?
Association between elevated Lp-PLA2 and cardiovascular events did not establish that the enzyme was a causal treatment target. Inhibition lowered target-related biomarkers but did not reduce major cardiovascular outcomes.
Can darapladib still be approved for a different indication?
Theoretically, yes, but approval would require new clinical evidence in the proposed indication. The prior Phase III failures materially increase development risk and would not support approval by themselves.
Is darapladib available as a generic drug?
No. Darapladib is not commercially approved, so no FDA-approved generic version is available.
Does darapladib have biosimilar competition?
No. Darapladib is a small molecule, not a biologic. Biosimilar competition is therefore not applicable.
What is the investment case for acquiring darapladib rights?
The investment case is limited to low-cost access to historical chemistry, biomarker data, or a repurposing option. A conventional commercial acquisition case is weak because the candidate lacks approval, failed two major outcomes trials, and has no current revenue base.
References
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Food and Drug Administration. (n.d.). Orange Book: Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services. https://www.accessdata.fda.gov/scripts/cder/ob/
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O'Donoghue, M. L., Braunwald, E., White, H. D., Murphy, S. A., Steg, P. G., Patel, A., ... SOLID-TIMI 52 Investigators. (2014). Effect of darapladib on major coronary events after an acute coronary syndrome: The SOLID-TIMI 52 randomized clinical trial. JAMA, 312(10), 1006-1015.
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White, H. D., Held, C., Stewart, R., Tarka, E., Brown, R., Davies, R. Y., ... STABILITY Investigators. (2014). Darapladib for preventing ischemic events in stable coronary heart disease. New England Journal of Medicine, 370(18), 1702-1711.
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ClinicalTrials.gov. (n.d.). STABILITY: Stabilization of atherosclerotic plaque by initiation of darapladib therapy. U.S. National Library of Medicine. https://clinicaltrials.gov/
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ClinicalTrials.gov. (n.d.). SOLID-TIMI 52: Stabilization of plaque by darapladib: Lipoprotein-associated phospholipase A2 inhibitor treatment in patients with acute coronary syndrome. U.S. National Library of Medicine. https://clinicaltrials.gov/
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