Sufferers with recessive X-linked and autosomal recessive lamellar congenital ichthyosis (CI) achieved therapy success with a novel topical isotretinoin ointment often known as TMB-001, outcomes from a section 2b examine demonstrated.
“Sufferers with these deficiencies have typically had very restricted therapy choices, together with lifelong use of emollients and keratolytics, and in extreme instances, systemic retinoids,” Christopher G. Bunick, MD, PhD, affiliate professor of dermatology at Yale College, New Haven, Conn., mentioned at a late-breaking summary session on the annual assembly of the American Academy of Dermatology. “There may be at present no [Food and Drug Administration]-approved drug for CI. So, think about your sufferers and their dad and mom, and the frustration they need to really feel.”
In a examine often known as CONTROL, he and his colleagues evaluated the impact of TMB-001 on two subtypes of congenital ichthyosis: X-linked recessive ichthyosis (XLRI) and autosomal recessive congenital ichthyosis–lamellar ichthyosis (ARCI-LI). Of the 2, the commonest is XLRI, which has an estimated incidence of 1:3,000 and is brought on by a deficiency of steroid sulfatase, leading to ldl cholesterol sulfate accumulation within the stratum corneum, retained corneodesmosomes, and diminished corneocyte desquamation, Bunick mentioned.
ARCI-LI is rarer, with a prevalence of 1:100,000, and has been linked to mutations in six genes, mostly TGM1, leading to enzyme inactivation and poor cross-linking of cornified cell envelope proteins.
TMB-001 is a proprietary, novel, topical isotretinoin formulation to deal with CI that’s being developed by Timber Prescription drugs. It makes use of a patented “IPEG” expertise isotretinoin supply system designed particularly for sufferers with CI. In a previous section 2a examine, TMB-001 0.1% and 0.2% ointment twice a day demonstrated larger enchancment in ≥ 1 and ≥ 2 Investigator International Evaluation (IGA) scores in contrast with car. Scaling in all sufferers handled with TMB-001 was thought of clear, nearly clear, or delicate at 8 weeks, and no regarding security alerts have been noticed.
For the present trial, 33 sufferers 9 years of age and older with genetically confirmed XLRI/ARCI-LI and ≥ 2 (out of 4) Visible Index for Ichthyosis Severity (VIIS) evaluation areas with a ≥ 3 scaling rating have been randomized 1:1:1 to TMB-001 0.05%, TMB-001 0.1%, or car twice day by day for 12 weeks. Main and secondary efficacy endpoints have been discount of ≥ 50% in contrast with baseline in VIIS-scaling (VIIS-50) and a ≥ 2-grade discount within the Investigator International Evaluation (IGA)–scaling rating in contrast with baseline. The sufferers ranged in age from 23 to 41 years, the bulk have been White, and their baseline physique floor space (BSA) affected ranged from 28% to 38%.
Of the 33 sufferers, 11 sufferers obtained TMB-001 0.05%, 10 obtained TMB-001 0.1%, and 12 obtained the car.
Amongst all sufferers, 55% had ARCI-LI and 45% had XLRI subtypes, and people with ARCI-LI had larger prior use of corticosteroid, emollient, and oral/topical retinoids. Total, 100%, 33%, and 75% of sufferers with XLRI and 50%, 50%, and 17% of sufferers with ARCI-LI achieved VIIS-50 after receiving TMB-001 0.05%, TMB-001 0.1%, and car, respectively.
An enchancment of a ≥ 2-grade IGA rating was noticed in 80%, 33%, and 25% of sufferers with XLRI and 50%, 50%, and none of sufferers with ARCI-LI who obtained TMB-001 0.05%, TMB-001 0.1%, and car, respectively (P =.018 for TMB-001 0.05% vs. car).
Bunick reported that there have been no critical opposed occasions, no hospitalizations, and no affected person deaths. Six sufferers discontinued therapy, 5 due to participant withdrawal and one due to doctor withdrawal. The 4 commonest treatment-emergent opposed occasions have been erythema (21%), pruritus (21%), ache (15%) and dermatitis (12%).
“These outcomes assist ongoing investigation of TMB-001 as a promising various to systemic retinoids for members with CI,” Bunick concluded. He famous that whereas he isn’t aware about particulars of TMB-001’s IPEG supply system, “the way in which they’ve used polyethylene glycol to encapsulate the isotretinoin permits for larger barrier penetration and reduces a whole lot of the tolerability points which are seen with different topical retinoids.” In his view, “that’s offering this retinoid a larger likelihood of success. The patented supply system is just not solely designed to assist the isotretinoin do its job, but in addition to supply that stability and the flexibility to compound it, which have been boundaries to success up to now.”
Part 3 trials of the agent are scheduled to start in June of 2022.
Amy S. Paller, MD, professor and chair of the division of dermatology at Northwestern College, Chicago, who was requested to touch upon the examine, mentioned that she was impressed that no important adjustments from baseline laboratory medical assessments have been noticed. “If that is true, then we do not have to be monitoring these sufferers in the identical method as with systemic brokers,” mentioned Paller, who was concerned within the section 2a proof-of-concept trial of TMB-001. “I feel that deserves extra investigation. Hopefully that will likely be checked out within the section 3 trial.”
Bunick reported having no disclosures associated to his presentation. Paller disclosed that she is marketing consultant to and/or an investigator for quite a few pharmaceutical corporations.
This text initially appeared on MDedge.com, a part of the Medscape Skilled Community.