Galderma / Aklief
TRIFAROTENE CREAM 0.005%
The same trial reports irritation in 7.5% of users and in 65% of users, depending on whether anyone asked. Both numbers are on the label, and the gap between them is the most useful thing in this review.
Worth buying for a specific person with a specific problem. Read who.
ASSESSED ON 75% OF THE MODEL. 2 CRITERIA LEFT UNSCORED — SEE SCORING FOR WHY.
We earn nothing on this link. Read the two irritation figures below before you decide — the 7.5% and the 65% describe the same trial.
The verdict
Trifarotene is the first new topical retinoid molecule approved in decades and the first selective for the RARγ receptor, which is the receptor most abundant in skin. It is also the only acne retinoid trialled on the trunk as a co-primary endpoint rather than an afterthought, in 2,420 subjects — the largest programme in this register.
The efficacy is solid and consistent with the class. Facial IGA success at twelve weeks reached 29.4% and 42.3% against 19.5% and 25.7% on vehicle, with truncal PGA success of 35.7% and 42.6% against 25.0% and 29.9%. Lesion reductions ran around 55% to 66% on inflammatory lesions. Nothing here is disappointing.
The reason to read this review is a methodological one that applies to every product in this register. The adverse reactions table reports application site irritation in 7.5% of subjects. A second table, from the same trials, reports actively assessed erythema worse than baseline in 65.2% of subjects and scaling worse than baseline in 69.5%. Same drug, same people, same twelve weeks — 7.5% when reactions were volunteered, and roughly two-thirds when investigators looked for them.
Two practical conclusions follow. Aklief is a more irritating retinoid than the tretinoin lotion at R-36, which reported 4% dryness against vehicle, and anyone choosing between them should know that. And more generally: an adverse-reaction percentage on any label is a floor, not an estimate. Very few products publish the actively-assessed version. This one does, at 45 g for around $693, which is the other reason it is conditional rather than recommended.
- Publishes an actively assessed tolerability table alongside the volunteered adverse reactions — almost no label does this.
- The largest registration programme in this register: 2,420 subjects.
- The only acne retinoid here with truncal efficacy measured as a formal endpoint.
- Facial and truncal results published separately, both trials.
- A one-year open-label safety trial in 453 subjects, with the discontinuation rate published at 2.9%.
- States that the frequency of adverse reactions decreased over time.
- Publishes sunburn incidence against vehicle — 2.6% against 0.5% — which most retinoid labels omit.
- Concentration stated in per cent and micrograms per gram, with the pack size published.
- First RARγ-selective retinoid, a genuinely new molecule rather than a reformulation.
- Actively assessed erythema worse than baseline in 65.2% of subjects and scaling in 69.5%.
- Severe erythema in 6.2% and severe scaling in 4.9%.
- The volunteered adverse reaction rate of 7.5% understates that by roughly ninefold.
- More irritating than the tretinoin lotion at R-36, which reported 4% dryness.
- Around $693 to $927 for a single 45 g pump, with no generic.
- Intended for face and trunk, which consumes product far faster than a facial-only retinoid.
- The two pivotal trials differ by thirteen points on the facial endpoint.
- 87% of subjects were Caucasian and 48% were under eighteen.
- Indicated for acne only — photoageing use is off-label.
- Pregnancy: retinoid class.
Every active, assessed
- Trifarotene0.005% — 50 mcg/g
Fourth-generation retinoid, selective for the RARγ receptor — the dominant retinoic acid receptor in skin
- BENCHMARK
- The lowest approved topical retinoid concentration; tretinoin runs 0.02% to 0.1%, tazarotene 0.045% to 0.1%
- ASSESSMENT
- A hundredth of a per cent, which sounds negligible and is not — receptor selectivity means potency does not track concentration across molecules. Comparing 0.005% trifarotene with 0.05% tretinoin as though the smaller number meant a milder drug is exactly the mistake this register keeps warning about, and the tolerability tables settle it: this is the more irritating of the two.
| ACTIVE | CONC. | BENCHMARK | ASSESSMENT |
|---|---|---|---|
| TrifaroteneFourth-generation retinoid, selective for the RARγ receptor — the dominant retinoic acid receptor in skin | 0.005% — 50 mcg/g | The lowest approved topical retinoid concentration; tretinoin runs 0.02% to 0.1%, tazarotene 0.045% to 0.1% | A hundredth of a per cent, which sounds negligible and is not — receptor selectivity means potency does not track concentration across molecules. Comparing 0.005% trifarotene with 0.05% tretinoin as though the smaller number meant a milder drug is exactly the mistake this register keeps warning about, and the tolerability tables settle it: this is the more irritating of the two. |
Scoring
- EVIDENCE FOR THE ACTIVEWEIGHT 30%74/100
Two identically designed vehicle-controlled trials in 2,420 subjects with co-primary facial endpoints and co-secondary truncal endpoints, plus a one-year open-label safety trial in 453 subjects. The largest programme here. Marked down because the effect size is ordinary for the class, because the two trials differ by thirteen points on the facial endpoint, and because 87% of subjects were Caucasian and 48% were under eighteen.
- FORMULATION INTEGRITYWEIGHT 20%62/100
A conventional cream in a 45 g pump at the trialled strength, with a published excipient list. Marked down because the formulation does nothing to address the tolerability its own actively-assessed tables record — roughly two-thirds of subjects with worse erythema and scaling than baseline, and 6.2% with severe erythema — at a time when competing retinoids are being reformulated specifically to solve that.
- DISCLOSUREWEIGHT 15%92/100
Publishes the actively assessed tolerability table alongside the volunteered adverse reactions, which almost nothing else does and which makes its own product look considerably worse. Also publishes facial and truncal results separately, both trials, the one-year open-label discontinuation rate of 2.9%, sunburn incidence against vehicle, and full demographics. Held back only because the two irritation figures are never reconciled for the reader.
- TOLERANCE IN USEWEIGHT 15%NOT ASSESSED
Not assessed by us, and uniquely for this register the label has done the work: erythema worse than baseline in 65.2% of facial subjects and scaling in 69.5%, against 28.6% and 29.9% on vehicle. A panel would add whether that is survivable in practice, which the 2.9% one-year discontinuation rate suggests it often is.
- TEXTURE & WEARWEIGHT 10%NOT ASSESSED
Not assessed. A cream in a metered pump, applied to face and trunk, which is a larger surface area than anything else in this register.
- COST PER APPLICATIONWEIGHT 10%24/100
Around $693 for a single 45 g pump against an average retail near $927, with no generic, for a product intended to cover face and trunk daily. The fill weight is published so the arithmetic is possible, and covering the trunk consumes product several times faster than a facial-only retinoid. The worst value in the retinoid class here.
What it is
Trifarotene 0.005% in a cream, applied once daily in the evening, approved for acne vulgaris of the face and trunk from age nine. A 45 g pump, around $693. It is the first RARγ-selective retinoid and the first approved for truncal acne on the strength of trials that actually measured it.
Two irritation figures from one trial
Section 6.1 of this label contains two tables. The first lists adverse reactions occurring in at least 1% of subjects — the reactions people reported, unprompted, when asked how they were getting on.
The second table reports the same signs, in the same subjects, in the same trials — but actively assessed by investigators at every visit, scored against each subject's own baseline.
N=1,214 on Aklief against 1,194 on vehicle. Bars show the total percentage of subjects recording each sign at any severity worse than their own baseline; the notes give the severity split. Against a volunteered irritation rate of 7.5%.
Nothing here is dishonest — both tables are on the label, correctly captioned, and publishing the second one is to Galderma's considerable credit, because it makes the product look far worse. But the gap is roughly ninefold, and it exists for a mundane reason: people do not spontaneously report expected side effects, and trials only capture what they are designed to capture. Every adverse-reaction percentage in this register, on every label we have quoted, is a floor rather than an estimate. This is the one label that lets you see by how much.
The other side of it is the one-year open-label trial: 12.6% of 453 subjects had at least one adverse reaction across the whole year, 2.9% discontinued because of one, and the frequency of reactions decreased over time. So two-thirds of people get visibly worse erythema at some point, and 97% of them carry on anyway. Both facts are true and neither is the whole picture.
What it does
Success required clear or almost clear plus a two-grade improvement. Face: N=612 and 602 on drug against 596 and 610 on vehicle. Trunk: N=600 and 598 against 585 and 609. The truncal endpoint is the distinguishing feature — no other retinoid here has one.
Inflammatory lesions fell 54.4% and 66.2% on the face against 44.8% and 51.2% on vehicle. Truncal inflammatory lesions fell 57.4% and 65.4% against 50.0% and 51.1%. The truncal vehicle response is high, which is worth noticing: half the improvement on the back and chest came from applying a cream consistently.
The truncal indication is the genuine differentiator. Acne on the back and shoulders is common, distressing and routinely undertreated because most topicals are studied on faces and sold in facial quantities. This one was trialled on both and its pump is sized accordingly — which also explains why it runs out faster.
Five thousandths of a per cent
0.005% is the lowest concentration of any approved retinoid, and it would be easy to read it as the gentlest. The tolerability tables say otherwise. Receptor selectivity and binding affinity determine potency; concentration only tells you how much molecule is in the tube.
That matters well beyond this product. This register has repeatedly found compounded formulas quoting tretinoin at 0.006%, 0.015% or 0.018% as though a smaller number meant a milder experience, and has criticised several for sitting below the trial range. Both things can be true at once: a concentration below the evidence base for its own molecule is a real problem, and a low number across different molecules means nothing at all. Aklief at 0.005% is more irritating than Altreno at 0.05%.
If you are considering it
- If your acne is facial only and you are paying cash, R-36 is better tolerated at a fifth of the price.
- If you have truncal acne, this is the one retinoid with a formal endpoint for it.
- Check coverage first. Cash and covered prices differ by hundreds of dollars.
- Expect visible erythema and scaling. Two-thirds of trial subjects had both, worse than their baseline, at some point.
- Start every other night if your prescriber agrees, and build up.
- Moisturise, and expect the reactions to ease — the one-year data show frequency falling over time.
- Sunscreen daily. The sunburn signal on this label is explicit and it is five times the vehicle rate.
- Give it twelve weeks. Both trials read out then.
- Do not read 0.005% as gentle.
Where we stand
At 68 this is a good drug with a bad price and an honest label, and the honesty is what makes it worth the space. Galderma published a table showing its own product produced worse erythema in nearly two-thirds of users. Almost nobody does that, and the entire register is better calibrated for having seen it.
The lesson to carry forward is simple. When any product — approved, compounded, prescription or cosmetic — quotes an irritation rate, ask whether anyone was asked or whether anyone looked. On the one label in this register that did both, the answers differed by a factor of nine.
4% dryness on a vehicle-controlled table — and a fifth of the price.
The other expensive branded retinoid, with a published discontinuation rate.
Why 0.005% and 0.05% cannot be compared across molecules.
What two-thirds of subjects with worse erythema does and does not mean.
Who this is for
- Someone with acne on the back, chest or shoulders as well as the face, where this is the only retinoid formally trialled for both.
- Someone with insurance coverage, without which the price is very hard to justify.
- Someone who has tolerated retinoids well before and wants a newer molecule.
- Anyone who wants to understand what a published adverse-reaction percentage does and does not mean.
- You are pregnant, trying to conceive or breastfeeding.
- Irritation is what stopped you on previous retinoids — R-36 is the better-tolerated and far cheaper option.
- You are paying cash and only need facial treatment.
- You spend a lot of time in strong sun and cannot commit to daily photoprotection — the sunburn signal here is explicit.
- You want data in an adult population; nearly half of these subjects were children or adolescents.
We earn nothing on this link. Read the two irritation figures below before you decide — the 7.5% and the 65% describe the same trial.
This is an editorial assessment of published information about a prescription product. It is not a diagnosis, not a prescription and not a substitute for your own prescriber. Hydroquinone and tretinoin are drugs. Decisions about them belong with a clinician who has seen your skin.
Sources
- S-01FDA-approved labelling — AKLIEF (trifarotene) cream, 0.005%, Galderma Laboratories, L.P. The 0.005% strength stated as 50 mcg per gram in a 45 g pump; the two 12-week trials (NCT02566369, NCT02556788) in 2,420 subjects with facial IGA success of 29.4% against 19.5% and 42.3% against 25.7%, truncal PGA success of 35.7% against 25.0% and 42.6% against 29.9%, and the inflammatory and non-inflammatory lesion reductions; Table 1 adverse reactions of application site irritation 7.5%, sunburn 2.6% and pruritus 2.4%; Table 2 actively assessed facial tolerability showing erythema mild 30.6%, moderate 28.4%, severe 6.2% and scaling mild 37.5%, moderate 27.1%, severe 4.9% against vehicle; the one-year open-label trial in 453 subjects with 12.6% experiencing an adverse reaction and 2.9% discontinuing; and the demographics of 87% Caucasian with 48% of subjects under eighteen. Read 2 August 2026.
- S-02GoodRx — Aklief pricing An average cost of about $693.04 for a 45 g pump with a discount card, against an average retail price near $927. Retrieved 2 August 2026.