High-power short-pulsed laser treatment in selective photothermolysis of sebaceous glands

Description

TITLEHIGH-POWER SHORT-PULSED LASER TREATMENT IN SELECTIVE PHOTOTHERMOLYSIS OF SEBACEOUS GLANDSRELATED APPLICATION

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 634,784, filed on April 16, 2024, the entire contents of which are incorporated herein by reference.FIELD

[0002] The present disclosure relates to a method of treating acne using a 1726 nm laser pulse that selectively targets and destroys sebocytes while sparing the epidermis.BACKGROUND

[0003] This invention relates generally to electromagnetic radiation-based medical treatment systems, and more specifically to delivering a laser pulse selectively to a target skin area in the treatment of dermatological conditions, such as acne.

[0004] Acne vulgaris, more commonly referred to simply as acne, is the most common reason for office visits to dermatologists in the United States. Acne vulgaris, a common inflammatory condition with a multifactorial pathogenesis, can occur at any life stage and profoundly impacts quality of life.

[0005] Over 60 million Americans suffer from acne. Treatment options include topical applications such as disinfectants (e.g., benzoyl peroxide), retinoids (e.g., Retin-A), and antibiotics (e.g., clindamycin and erythromycin), as well as ingested compounds such as antibiotics (e.g., tetracycline), hormonal treatments (e.g., birth control pills), isotretinoin (Accutane, which has significant side effects), and optical treatments such as laser treatments, which have the benefit of avoiding the side effects and inconvenience of pharmaceuticals and topical treatments but which, at present, have limited effectiveness for a variety of reasons including the previously noted problems of skin tissue complexity and the limitations of existing laser systems. More recently, nanosphere particles have been deposited into skin pores and / or follicles, followed by heating of the nanoparticles with laser light to treat acne.

[0006] In U.S. Pat. No. 8,474,463, a treatment system for acne vulgaris is described that uses a pulsed laser to damage sebaceous gland tissue. The system uses alaser having a wavelength in the range of 800 nm and 1200 nm, with pulses having a peak power of 10-14 kW for pulses in the range of 100-3000 psec, a pulse repetition rate of 2-12 Hz, and a fluence of at least 8 J / cm2, typically 10-20 J / cm2. The system of the ‘463 patent, however, lacks the precise control of temperature necessary to achieve with consistency both a desired damage level to the target structure and avoid or limit damage to overlying structures.

[0007] While offering substantial improvement to many patients, current topical and systemic therapies are not effective or tolerated in all cases. (Goldberg D, Kothare A, Doucette M, Kaur A, et al. Selective photothermolysis with a novel 1726 nm laser beam: A safe and effective solution for acne vulgaris. J Cosmet. Dermatol., 2023;22(2):486-496).

[0008] Lack of early effective treatment raises the risk of lasting erythema, post- inflammatory hyperpigmentation (PIH), and scarring. (Tan J, Kang S, Leyden J. Prevalence and risk factors of acne scarring among patients consulting dermatologists in the United States. J Drugs Dermatol. 2017;16(2):97-102).

[0009] There is a need for a treatment method that is selective for sebaceous glands and be able to treat acne ensuring effectiveness, durable response and safety.SUMMARY

[0010] The embodiments of the present disclosure provide a method of treating acne in a patient comprising irradiating a sebum or a sebaceous gland within a target skin area with a spot of a therapeutic laser pulse having a wavelength of about 1726 nm, and continuing said treatment until the acne has subsided or cleared, wherein at least half of the acne was resolved after treatment, wherein the patient showed an Investigator’s Global Assessment (IGA) score of either +1 or +2, and wherein the treatment resulted in a reduction of inflammatory lesion count and a reduction of nodule count.

[0011] In the methods of the disclosure, the patient received at least three treatment sessions that are spaced about 4 weeks apart.

[0012] The treatment in the said methods of the disclosure resulted in a reduction of inflammatory lesion count (ILC) and nodule count.

[0013] In some aspects, the treatment resulted in about 80% reduction of inflammatory lesion count. In some aspects, the treatment resulted in about 85% reduction of inflammatory lesion count. In some aspects, the treatment resulted inabout 90% reduction of inflammatory lesion count. In some aspects, the treatment resulted in about 95% reduction of inflammatory lesion count.

[0014] In some aspects, the treatment resulted in about 70% reduction of nodule count. In some aspects, the treatment resulted in about 75% reduction of nodule count. In some aspects, the treatment resulted in about 80% reduction of nodule count. In some aspects, the treatment resulted in about 85% reduction of nodule count. In some aspects, the treatment resulted in about 90% reduction of nodule count. In some aspects, the treatment resulted in about 95% reduction of nodule count.

[0015] In one aspect of the disclosure, the treatment inhibited sebum production and the treatment destroyed sebocytes.

[0016] The mean pain score of the patient was from about 5.0 to about 5.6 following the treatment of the disclosure.

[0017] The median pain score of the patient was from about 5.2 to about 5.7 following the treatment of the disclosure.

[0018] The treatment disclosed herein did not result in hyperpigmentation or hypopigmentation in the patient.

[0019] The treatment disclosed herein applies to patients with Fitzpatrick skin types.

[0020] The acne treated by the said method of the disclosure is selected from acne vulgaris, truncal acne, hormonal acne, or acne rosacea. In specific aspects, the acne is acne vulgaris.

[0021] The acne treated by the said method of the disclosure is mild, moderate or severe.

[0022] In the methods of treating acne in a patient, the sebum or a sebaceous gland within a target skin area is irradiated. The target skin area of the patient is said to include forehead, face, lip area, chin, cheeks, and nose.

[0023] The patient undergong the treatment disclosed herein is atleast 16 years of age or older.

[0024] In one aspect of the disclosure, the treatment can further comprise a combination therapy. The combination therapy comprises concomitant administration of topical acne medications to the patient in need thereof. In some aspect, the topical acne medications comprises retinoids, antibiotics, hormonal agents, benozyl peroxide (BPO), or any combination thereof.BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Fig. 1A shows the histology staining of healthy sebaceous gland with nucleated sebocytes (pre-treatment). Fig. 1 B shows the magnified histology staining of the damaged sebaceous gland. Fig. 1 C shows the histology staining 5 days posttreatment.

[0026] Fig. 2 is a plot showing the percentage improvement in Inflammatory Lesion Count (ILC) in subjects at 3, 6, and 12-months of treatment.

[0027] Fig. 3A is a plot showing the mean % change from baseline in ILC for patients taking sarecycline compared with placebo (ITT population). Fig. 3B is a plot showing the mean % change from baseline in ILC for patients taking sarecycline compared with placebo (ITT population).

[0028] Fig. 4 is a comparison of ILC reduction and shows the mean % change in ILC with leading tropicals, leading oral AB, Aviclear and Isotretinoin respectively.

[0029] Fig. 5 is a plot showing the percentage improvement in Comedonal Count in subjects at 3, 6, and 12-months of treatment.

[0030] Fig. 6 is a plot showing the percentage improvement of Investigator’s Global Assessment (IGA) score of +1 at 3, 6, and 12-months of treatment.

[0031] Fig. 7 is a plot showing the percentage improvement of Investigator’s Global Assessment (IGA) score of +2 at 3, 6, and 12-months of treatment.

[0032] Fig. 8 is a plot showing the percentage reduction in Nodule Count Reduction at 3, 6, and 12-months of treatment.

[0033] Fig. 9 is a plot showing the treatment efficacy at 3, 6, and 12-months of treatment.

[0034] Fig. 10 is a plot showing the mean patient score per patient at 3, 6, and 12- months of treatment.

[0035] Fig. 11 is a plot showing the percentage acneiform flare-up (purging) over a time period in which the purging takes place.

[0036] Fig. 12 shows the VAS numeric pain scale.

[0037] Fig. 13A shows that over 80% of patients saw visual improvement in their skin at 6- and 12-months post three 1726 nm treatments and were satisfied that their skin looks better. Fig. 13B shows that over 80% of patients saw visual improvement in their skin at 6- and 12-months post three treatments and were satisfied that their skin is smoother.

[0038] Fig. 14 is a plot of satisfaction with results at 3, 6 and 12-months of treatment.

[0039] Fig. 15A is a plot that shows the selective absorption of sebum at 1726 nm when compared to water. Fig. 15B is a plot that shows the laser optimized selectivity at 1726 nm.

[0040] Fig. 16 shows the differentiation of 1726 nm from other energy based devices (EBD).

[0041] FIG. 17 is a schematic depiciting the design of a 3-month follow-up study that includes topical therapies while undergoing acne therapy with a 1726 nm laser.

[0042] FIG. 18 is a pie chart that shows the distribution of patients on concomitant medications (N=21 ).

[0043] FIG. 19A is a baseline picture of a subject with moderate IGA. FIG. 19B is a picture of the treated subject showing clear IGA at 3 months after the third treatment.

[0044] FIG. 20A is a baseline picture of a subject with severe IGA. FIG. 20B is a picture of the treated subject showing almost clear IGA at 3 months after the third treatment.

[0045] FIG. 21 is a schematic depicting the design of the pivotal efficacy study.

[0046] FIG. 22A shows the age distribution of male and female patients of the pivotal study. FIG. 22B shows the distribution of acne seventy (mild, moderate and severe) in patients of the pivotal study. FIG. 22C shows the distribution of Fitzpatrick skin types (l-IV) of the patients in the pivotal study.

[0047] FIG. 23 is a plot showing the patient satisfaction of the one-year outcome study at 3-month, 6-month and 12-month period of time.

[0048] FIG. 24 shows the absolute median inflammatory acne lesion counts and percent change from baseline (PP cohort) at week 4, week 12, week 26 and week 52 respectively.

[0049] FIG. 25A is a baseline picture of a subject with moderate IGA. FIG. 25B is a picture of the treated subject showing clear IGA at 6 months after the third treatment. FIG. 25C is a picture of the treated subject showing clear IGA at 12 months after the third treatment.

[0050] FIG. 26A is a baseline picture of a subject with moderate IGA. FIG. 26B is a picture of the treated subject showing mild IGA at 6 months after the third treatment. FIG. 26C is a picture of the treated subject showing almost clear IGA at 12 months after the third treatment.

[0051] FIG. 27A is a baseline picture of a subject with moderate IGA. FIG. 27B is a picture of the treated subject, satisfied and showing mild IGA at 12 week follow-up.FIG. 27C is a picture of the treated subject, satisfied and showing mild IGA at 26 week follow-up. FIG. 27D is a picture of the treated subject, extremely satisfied and showing almost clear IGA at 52 week follow-up.

[0052] FIG. 28A is a baseline picture of a subject. FIG. 28B is a picture of the treated subject at 6 months after the third treatment. FIG. 28C is a picture of the treated subject at 12 months (1 year) after the third treatment. FIG. 28D is a picture of the treated subject at 33 months (about 2.75 years) after the third treatment.DETAILED DESCRIPTION

[0053] Exemplary embodiments of the present disclosure are illustrated in the drawings, which are illustrative rather than restrictive. No limitation on the scope of the technology, or on the claims that follow, is to be implied or inferred from the examples shown in the drawings and discussed herein.

[0054] This disclosure relates to treatment of acne, more specifically, acne vulgaris in a patient. It involves using a laser light pulse of about 1726 nm to irradiate and heat a target skin area to thermally damage a selected structure within the target skin area. The treatment with 1726 nm laser is continued until acne has subsided or cleared.

[0055] The lack of selectivity for sebaceous glands has limited the value of laser therapy for acne, with most laser treatments focusing on temporary reduction of lesions. Selective photothermolysis with AviClear ensures effectiveness, durable response, and safety. The high-powered contact cooling system not only improves the safety margin but also helps to manage discomfort during the treatments.Bhatia, AC et al. provides a practical guidance to optimize outcomes with AviClear, a novel laser treatment for acne that will help clinicians gain comfort with the modality and use. (Bhatia, AC et al. The Dermatology Digest, March 2024, pgs. 36- 37, incorporated by reference in its entirety).

[0056] The laser energy is selected such that it minimizes damage to non-target tissues and depends upon factors such as the laser power, fluence, spot size, etc. used in a treatement. The laser energy is delivered with the perfect convergence of spot size and pulse duration to reach the sebaceous glands at the nominal wavelength of about 1726 nm. In aspects of this disclosure, the duration of the laser treatment pulse can be up to about 50 ms. In other aspects, the maximum output power of the laser is about 100 W. In yet another aspect, the maximum energyfluence is about 30 J / cm2. The spot size can be a 3 mm single spot or a 10 mm 7- spot hexagonal array.

[0057] The patients or subjects saw at least half of their acne resolved after treatment. The patients also showed an Investigator’s Global Assessment (IGA) score of either +1 or +2.

[0058] The treatment methods of the disclosure resulted in a reduction of inflammatory lesion count and a reduction of nodule count.

[0059] In aspects of the disclosure, the patients receive at least three treatments that are spaced about 4 weeks apart. In some aspects, the patients are also evaluated in their follow-up visits at about 1 , about 3, about 6, and about 12 months post final treatment.

[0060] In aspects of the disclosure, the endpoints of this treatment include a primary endpoint (% of patients achieving at least a 50% reduction in inflammatory acne lesion (ILC) counts). Secondary endpoints include IGA improvement, reduction in comedonal acne lesion counts, and subject satisfaction.

[0061] In one such aspect, the patient getting treated for acne showed a visible improvement at the end of their treatment.

[0062] In one specific aspect, the patient saw at least half of their acne resolved at about 3 months after the final treatment. In another specific aspect, the patient saw at least half of their acne resolved at about 6 months after the final treatment. In another specific aspect, the patient saw at least half of their acne resolved at about 12 months after the final treatment and were assessed as clear or almost-clear of acne.

[0063] In one such aspect, the patient getting treated for acne showed +1 Investigator’s Global Assessment (IGA) improvement score at about 3 months after the final treatment.

[0064] In one such aspect, the patient getting treated for acne showed +2 Investigator’s Global Assessment (IGA) improvement score at about 3 months after the final treatment.

[0065] In one such aspect, the patient getting treated for acne showed +1 Investigator’s Global Assessment (IGA) improvement score at about 6 months after the final treatment.

[0066] In one such aspect, the patient getting treated for acne showed +2 Investigator’s Global Assessment (IGA) improvement score at about 6 months after the final treatment.

[0067] In one such aspect, the patient getting treated for acne showed +1 Investigator’s Global Assessment (IGA) improvement score at about 12 months after the final treatment.

[0068] In one such aspect, the patient getting treated for acne showed +2 Investigator’s Global Assessment (IGA) improvement score at about 12 months after the final treatment.

[0069] In one aspect, the treatment resulted in a reduction in inflammatory lesion count (ILC) and also a reduction in nodule count in a patient.

[0070] In one aspect, the treatment resulted in a reduction of about 80% to about 95% of inflammatory lesion count in a patient.

[0071] In one aspect, the treatment resulted in a reduction of about 70% to about 95% of nodule count in a patient during the treatment.

[0072] In one aspect, moderate and severe acne patients showed about 93% reduction in mean nodule count at about six months after the final treatment.

[0073] In one aspect, the treatment inhibited sebum production and destroyed sebocytes, while sparing the epidermis. No treatment related hyperpigmentation or hypopigmentation were observed.

[0074] In one aspect, the treatment is effective on all Fitzpatrick skin types.

[0075] In one aspect, the acne that is treated by the said method of treatment is selected from acne vulgaris, truncal acne, hormonal acne, or acne rosacea.

[0076] In specific aspects, the acne is acne vulgaris.

[0077] Without wishing to be bound by any theory, the treatment methods disclosed herein can be applied for treating acne that may be noninflammatory or inflammatory. Sub-types of acne that can be treated, can include, but not limited to, whiteheads, blackheads, papules, pustules, nodules, cysts, acne excoriee, acne mechanica, acne as a medication side effect, nodulocystic acne and acne conglobate. One embodiment is the treatment of inflammatory acne.

[0078] In some aspects, the methods provides for alleviation of the acne symptoms as well as preventing acne recurrence and new acne from occurring.

[0079] In one aspect, the treatment can be applied to patients with all acne seventies (mild, moderate, severe) with a high safety margin.

[0080] The treatment disclosed herein is a monotherapy. Patients undergoing this treatment tolerated discomfort without the need for a topical anesthetic.

[0081] In aspects of the disclosure, the patients getting treated for acne are at least 16 years of age or older.

[0082] Definitions

[0083] Applicant specifically incorporates the entire contents of all cited references in this disclosure. Further, when an amount, concentration, or other value or parameter is given as either a range or a list of upper values and lower values, this is to be understood as specifically disclosing all ranges formed from any pair of any upper range limit or value and any lower range limit or value, regardless of whether ranges are separately disclosed. Where a range of numerical values is recited herein, unless otherwise stated, the range is intended to include the endpoints thereof, and all integers and fractions within the range. It is not intended that the scope of the present disclosure be limited to the specific values recited when defining a range.

[0084] The indefinite articles “a” and “an”, as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to mean “at least one”.

[0085] The phrase “and / or”, as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Other elements may optionally be present other than the elements specifically identified by the “and / or” clause, whether related or unrelated to those elements specifically identified unless clearly indicated to the contrary. Thus, as a non-limiting example, a reference to “A and / or B”, when used in conjunction with open- ended language such as “comprising” can refer, in one embodiment, to A without B (optionally including elements other than B); in another embodiment, to B without A (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.

[0086] As used herein in the specification and in the claims, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating items in a list, “or” or “and / or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of’ or “exactly one of’, or, when used in the claims,“consisting of”, will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e., “one or the other but not both”) when preceded by terms of exclusivity, “either”, “one of’, “only one of”, “exactly one of”. “Consisting essentially of”, when used in the claims, shall have its ordinary meaning as used in the field of patent law.

[0087] The term “about” as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20%, ±10%, ±5%, ±1 %, or ±0.1 % from the specified value, as such variations are appropriate to perform the disclosed methods.

[0088] As used herein, “target skin area” refers to the skin receiving the energy of a laser pulse. The target skin area may include the surface skin area illuminated by the laser pulse, as well as deeper structures beneath the surface skin that receive at least a portion of the energy from the laser pulse. As such, “target skin areas” treated by a laser pulse may refer to a volume of skin as opposed to a true area of an outer surface of the epidermis.

[0089] As used herein, “Fitzpatrick skin type” also referred as “Fitzpatrick scale” is a numerical classification scheme for human skin color and is a well-recognized tool for dermatological research.

[0090] As used herein, the terms “treat,” “treating” or “treatment” refer to an action to obtain a beneficial or desired clinical result including, but not limited to, alleviation or amelioration of one or more signs or symptoms of acne (e.g., scars, pigmentation), diminishing the extent of acne (i.e., clearance of acne post treatment), diminishing rate of spreading of acne. In certain embodiments, the efficacy of the treatment by a qualified individual, e.g., a dermatologist, can be evaluated using accepted assessment tools of pain and quality of life (QOL) such as, but not limited to Global Acne Grading System (GAGS), and Investigator Global Assessment of Acne (IGA).

[0091] Dermatological systems and methods for providing a therapeutic laser treatment are disclosed in US 10,864,380 B1 , US 11 ,253,720 B2, US 11 ,400,308 B2, US 11 ,738,206 B2, US 2022 / 0168590 A1 , US 2022 / 0212026 A1 , US 2022 / 0212027 A1 , and US 2023 / 0302294 A1 ; each of which incorporated by reference herein in its entirety.EXAMPLES

[0092] Example 1

[0093] Histology Evalutation. Fig. 1A shows the histology staining of healthy sebaceous gland with nucleated sebocytes (pre-treatment). Fig. 1 B shows the magnified histology staining of the damaged sebaceous gland. Fig. 1 C shows the histology staining 5 days post-treatment. As seen from Fig. 1 C, the treatment stopped sebaceous glands from producing sebum without compromising the epidermis and destroys nucleated sebocytes. The damage through the length of the sebaceous gland shown in Fig. 1 C indicates sebocytes cell death.

[0094] Example 2

[0095] Inflammatory Lesion Count Improvement. Fig. 2 is a plot showing the % improvement in Inflammatory Lesion Count (ILC) in subjects at 3, 6, and 12-months of treatment. The ILC improvement of 50% and above was observed at the end of treatment. Fig. 2 shows that 80% of patients saw at least half of their acne resolved at three months after the final treatment. 87% of patients saw at least half of their acne resolved at six months after the final treatment. 92% of patients saw at least half of their acne resolved at twelve months after the final treatment.

[0096] Fig. 3A is a plot showing the mean % change from baseline in ILC for patients taking sarecycline compared with placebo (ITT population). Fig. 3B is a plot showing the mean % change from baseline in ILC for patients taking sarecycline compared with placebo (ITT population).

[0097] Fig. 4 is a comparison of ILC reduction and shows the mean % change in ILC with leading tropicals, leading oral AB, Aviclear and Isotretinoin respectively.

[0098] Example 3

[0099] Comedonal Count Improvement. Fig. 5 is a plot showing the percentage improvement in Comedonal Count in subjects at 3, 6, and 12-months of treatment. The Comedonal Count improvement of 50% and above was observed at the end of treatment. Fig. 5 shows that 13% of patients saw improvement in Comedonal Count at three months after the final treatment. 22% of patients saw improvement in Comedonal Count at six months after the final treatment. 39% of patients saw improvement in Comedonal Count at twelve months after the final treatment.F01001 Example 4

[0101] IGA Improvement +1 at 3, 6, and 12-months. Fig. 6 is a plot showing the percentage improvement of Investigator’s Global Assessment (IGA) score of +1 at 3,6, and 12-months of treatment. Fig. 6 shows that 87% of patients showed a +1 IGA improvement score at at three months after the final treatment. 90% of patients showed a +1 IGA improvement score at six months after the final treatment. 93% of patients showed a +1 IGA improvement score at twelve months after the final treatment.

[0102] Example 5

[0103] IGA Improvement +2 at 3, 6, and 12-months. Fig. 7 is a plot showing the percentage improvement of Investigator’s Global Assessment (IGA) score of +2 at 3, 6, and 12-months of treatment. Fig. 7 shows that 46% of patients showed a +2 IGA improvement score at at three months after the final treatment. 52% of patients showed a +2 IGA improvement score at six months after the final treatment. 73% of patients showed a +2 IGA improvement score at twelve months after the final treatment.

[0104] Example 6

[0105] Nodule Count Reduction at 3, 6, and 12-months. Fig. 8 is a plot showing the percentage reduction in Nodule Count Reduction at 3, 6, and 12-months of treatment. Fig. 8 shows that 71 % of nodules were reduced in patients at three months after the final treatment. 98% of nodules were reduced in patients at six months after the final treatment. 88% of nodules were reduced in patients at twelve months after the final treatment.F01061 Example 7

[0107] Efficacy of Treatment at 3, 6, and 12-months. Fig. 9 is a plot showing the treatment efficacy at 3, 6, and 12-months of treatment. Fig. 9 shows that 90% of patients showed visible improvement at six months after the final treatment. Moderate and severe acne patients had a 93% reduction in mean nodule count at six months after the final treatment. 2 out of 3 patients were assessed as clear or almost-clear at twelve months after the treatment. The procedure efficacy is presented in Table 1 . The patient experience is summarized in Table 2.

[0108] Table 1 : Procedure Efficacy at 3, 6, and 12-months of treatment.

[0109] Table 2: Patient Experience at 3 and 6-months of treatment.F01101 Example 8

[0111] Treatment-related Discomfort. Fig. 10 is a plot showing the mean patient score per patient at 3, 6, and 12-months of treatment. All patients tolerated treatment well without the need for topical anesthetic. No treatment sessions ended prematrurely due to discomfort. The mean pain score and median pain score are presented in Table 3.

[0112] Table 3: Pain score at 3, 6, and 12-months of treatment.F01131 Example 9

[0114] Treatment Response: Erythema and Edema. Erythema and edema lasted from one hour to two days with no prolonged patient downtime. No unexpected or serious treatment response or side effects were observed. No treatment related hyperpigmentation or hypopigmentation were observed. The laser-related adverse events are presented in Table 4.

[0115] Table 4: Laser device related adverse events >1 % (n=104).

[0116] Fig. 11 is a plot showing the percentage acneiform flare-up (purging) over a time period in which the purging takes place. The treatment sessions are spaced a few weeks apart. Tx1-Tx2 denotes the time period between treatments 1 and 2. Tx2-Tx3 denotes the time period between treatments 2 and 3. Tx3-4wkfu denotes the time period between the 3rdand the 4thweek follow-up after treatment 3. Transient acneiform flare-ups were a mild one-time event for most patients with a little over half of the flare-ups occurring post treatment 1 . A strong majority of acneiform flare-ups typically resolved within 6-weeks of treatment.

[0117] Example 10

[0118] Efficacy Improvement at 12 and 18-months. The improvement in efficacy at 12 months and 18 months is presented in Table 5. Patients at 18 months stay on acne medications 1-2 months into treatment. One patient did not respond. Two patients treated a second time at 18-month.

[0119] Table 5: Efficacy Improvement at 12 and 18-months.F01201 Example 11

[0121] Patient Comfort. The treatment disclosed herein maintain patient comfort and spare the epidermis. No topical anesthetic was used. Pain mitigation was not necessary in the patients. Average VAS score during treatment was 5.2 out of 10. No patient dropped out of treatment. No treatments ended prematurely due to discomfort. Fig. 12 shows the VAS numeric pain scale.F01221 Example 12

[0123] Patient Satisfaction. Fig. 13A shows that over 80% of patients saw visual improvement in their skin at 6- and 12-months post three 1726 nm treatments and were satisfied that their skin looks better. Fig. 13B shows that over 80% of patients saw visual improvement in their skin at 6- and 12-months post three treatments and were satisfied that their skin is smoother.

[0124] Fig. 14 is a plot of satisfaction with results at 3, 6 and 12 months of treatment. Satisfaction, defined as being “satisfied” or “very satisfied” with improvement after 3 treatments, was maintained through 1 year after last 1726 nm treatment. The satisfaction with results is further emphasized by the large number of subjects completing the study with no additional acne therapies utilized during the 1-year follow-up period post last 1726 nm treatment.F01251 Example 13

[0126] Therapeutic Laser. The method of treating acne disclosed herein employs a therapeutic laser having a wavelength of about 1726 nm to irradiate a sebum or a sebaceous gland within a target skin area with a spot of a laser pulse.

[0127] The wavelength of 1726 nm selectively targets sebum with at least twice the energy absorption of water to destroy sebocytes and suppress sebum production (Sakamoto FH, et al. Selective photothermolysis to target sebaceous glands: theoretical estimation of parameters and preliminary results using a free electron laser. Lasers Surg Med. 2012;44(2): 175-183; Scopelleti M, et al. A Novel 1726-nm Laser System for Safe and Effective Treatment of Acne Vulgaris. Lasers in Medical Science. 2022, the contents of which is incorporated by reference).

[0128] Fig. 15A is a plot that shows the selective absorption of sebum at 1726 nm when compared to water. Fig. 15B is a plot that shows the laser optimized selectivity at 1726 nm.

[0129] The wavelength of 1726 nm selectively targets and damages sebocytes.

[0130] The 100W power enables the perfect convergence of spot size and pulse duration at the proper wavelength to specifically target the sebaceous glands.

[0131] The sapphire cooling technology maintains the temperatue fo the skin during treatment to increase comfort while sparing the epidermis. (Scopelleti M, et al. A Novel 1726-nm Laser System for Safe and Effective Treatment of Acne Vulgaris. Lasers in Medical Science. 2022, the contents of which is incorporated by reference).

[0132] After treatment, sebaceous glands shrink and sebum production decreases.

[0133] The 1726 nm laser demonstrates durable therapeutic coutcomes and tolerability for moderate-to-severe acne across skin types (Alexiades M, et al.Journal of American Academy of Dermatology, 2023), the entire contents of which is incorporated by reference.

[0134] The use of 1726 nm laser as a safe alternative to to treat acne was disclosed by Goldberg DJ et al. in Journal of Cosmetic Dermatology, 2023, 00:1-7 and in Journal of Cosmetic Dermatology, 2022, 00:1-11 , the entire contents of which are incorporated by reference.

[0135] Fig. 16 shows the differentiation of 1726 nm from other energy based devices (EBD). Fig. 16 is a venn diagram showing a subset of patients that could benefit the most from the treatment of the disclosure. All patients can benefit and some patients can have all the issues.

[0136] The technical specifications of 1726 nm laser is given in Table 6.

[0137] Table 6: 1726 nm Laser Specifications.F01381 Example 14

[0139] 3-Month Follow-up Study-Treatment of Acne Vulgaris. Acne is a disease of the pilosebaceous unit. It involves abnormalities in sebum production, follicular epithelial desquamation, bacterial proliferation, and inflammation. Several classes of therapeutic agents such as, but not limited to, topical and systemic retinoids, topical and oral hormonal drugs, topical and oral antibiotic have been used in combination therapies for the treatment of moderate and severe acne (Zaenglein AL, et al. J. American Academy of Dermatol. 2016;74(5):945-973.e33).

[0140] The safety and efficacy of additional treatment in conjunction with the 1726 nm laser treatment for patients with severe acne are unknown.

[0141] This study evaluates the combination therapies that may serve beneficial in a subject while undergoing treatment of acne vulgaris with the seboselective 1726 nm laser.

[0142] In some aspects, the method of treatment of the disclosure can further comprise a combination therapy. For instance, the patients undergoing the 1726 nm laser treatment can concomitantly be administered with topical acne medications to treat acne vulgaris. The choice of topical agent is based on patient age, acne sites and seventy, and patient preference. The topical therapies can include, but notlimited to, retinoids, antibiotics, hormonal agents, benzoyl peroxide (BPO) or a combination thereof.

[0143] The study design included 45 subjects who received three treatments with the 1726 nm laser at 3-5 week intervals. 22 of 45 subjects were on an acne regimen at baseline, and remained on the same routine throughout the study. The subjects were assessed at 12 weeks post third treatment via the Investigator Global Assessment Scale (IGA). FIG. 17 schematically depicts the study design of 3-month follow-up study.

[0144] The study data for the 3-month outcome included 50 patients with Fitzpatrick skin type l-V. The average age of patients in this study were about 22 years. The age range of patients in this study were from about 16 years to about 43 years.About 70% of patients had moderate acne and about 30% of the patients had severe acne.

[0145] The endpoints and safety aspects of this 3-month outcome study is presented in Table 7. The distribution of patients on concomitant medications is shown in FIG. 18.

[0146] Table 7: Study Data: 3-Month Outcomes.

[0147] FIG. 19 shows the treatment results of a subject administered with Dapsone (a sulfone antibiotic), a combination of clindamycin and benzoyl peroxide (topical antibiotics) and spironolactone (a hormonal agent). FIG. 19A is a baseline picture of a subject with moderate IGA. FIG. 19B is a picture of the treated subject showing clear IGA at 3 months after the third treatment.

[0148] FIG. 20 shows the treatment results of a subject administered with a monotherapy. FIG. 20A is a baseline picture of a subject with severe IGA. FIG. 20B is a picture of the treated subject showing almost clear IGA at 3 months after the third treatment.

[0149] The interim analysis of the results from the 12-week follow up study show that combination therapy treatment with the 1726 nm laser in conjunction with other acne mediactions is safe and an effective approach to treat acne vulgaris.

[0150] Example 15

[0151] One Year Follow-up Study-Treatment of Acne Vulgaris. This is a pivotal study that is aimed to understand the efficacy of the 1726 nm phototherapy laser device in treating acne vulgaris. FIG. 21 schematically depicts the study design of this one year follow-up study.

[0152] The primary endpoint of this study included responser rate which is the percentage with > 50% ILC reduction. The secondary endpoints are Investigators Global Assessment (IGA) Improvement (% clear / almost clear), inflammatory lesion count (ILC) reduction, non-inflammatory lesion count (NILC) reduction and patient satisfaction. The study also monitors adverse events for safety measures.

[0153] The patient demographics (Alexiades M. et al. Journal of American Academy of Dermatology, 2023) for this pivotal study is shown in FIG. 22. FIG. 22A shows the age distribution of male and female patients of the pivotal study. FIG. 22B shows the distribution of acne seventy (mild, moderate and severe) in patients of the pivotal study. FIG. 22C shows the distribution of Fitzpatrick skin types ( l-IV) of the patients in the pivotal study.

[0154] The endpoints and safety aspects of this 1-year outcome study is presented in Table 8.

[0155] Table 8: Study Data: 1-Year Outcomes.

[0156] FIG. 23 shows the patient satisfaction of the one-year outcome study at the 3- month, 6-month and 12-month period of time.

[0157] FIG. 24 shows the absolute median inflammatory acne lesion counts and percent change from baseline (PP cohort) at week 4, week 12, week 26 and week 52 respectively.

[0158] FIG. 25A is a baseline picture of a subject with moderate IGA. FIG. 25B is a picture of the treated subject showing clear IGA at 6 months after the third treatment. FIG. 25C is a picture of the treated subject showing clear IGA at 12 months after the third treatment.

[0159] FIG. 26A is a baseline picture of a subject with moderate IGA. FIG. 26B is a picture of the treated subject showing mild IGA at 6 months after the third treatment. FIG. 26C is a picture of the treated subject showing almost clear IGA at 12 months after the third treatment.

[0160] FIG. 27 shows the IGA improvement and patient satisfaction over time. FIG. 27A is a baseline picture of a subject with moderate IGA. FIG. 27B is a picture of the treated subject, satisfied and showing mild IGA at 12 week follow-up. FIG. 27C is a picture of the treated subject, satisfied and showing mild IGA at 26 week followup. FIG. 27D is a picture of the treated subject, extremely satisfied and showing almost clear IGA at 52 week follow-up.

[0161] FIG. 28 shows the long term results of a subject at 33 months. FIG. 28A is a baseline picture of a subject. FIG. 28B is a picture of the treated subject at 6 months after the third treatment. FIG. 28C is a picture of the treated subject at 12 months (1 year) after the third treatment. FIG. 28D is a picture of the treated subject at 33 months (about 2.75 years) after the third treatment.

[0162] The results of this long term efficacy study shows the improvement in lesion count, acne seventy, and self-reported patient confidence that continued to improve over time. This study also demonstrates the safety and efficacy without the use of systemic medications. Further, this study provides evidence supporting the selective 1726 nm laser as a durable solution for managing acne vulgaris.

Claims

CLAIMSWhat is claimed is:1 . A method of treating acne in a patient comprising: irradiating a sebum or a sebaceous gland within a target skin area with a spot of a therapeutic laser pulse having a wavelength of about 1726 nm, and continuing said treatment until the acne has subsided or cleared, wherein at least half of the acne was resolved after treatment, wherein the patient showed an Investigator’s Global Assessment (IGA) score of either +1 or +2, and wherein the treatment resulted in a reduction of inflammatory lesion count and a reduction of nodule count.

2. The method of claim 1 , wherein the patient received at least three treatment sessions that are spaced about 4 weeks apart.

3. The method of claim 1 , wherein the treatment resulted in about 80% reduction of inflammatory lesion count.

4. The method of claim 1 , wherein the treatment resulted in about 85% reduction of inflammatory lesion count.

5. The method of claim 1 , wherein the treatment resulted in about 90% reduction of inflammatory lesion count.

6. The method of claim 1 , wherein the treatment resulted in about 95% reduction of inflammatory lesion count.

7. The method of claim 1 , wherein the treatment resulted in about 70% reduction of nodule count.

8. The method of claim 1 , wherein the treatment resulted in about 75% reduction of nodule count.

9. The method of claim 1 , wherein the treatment resulted in about 80% reduction of nodule count.

10. The method of claim 1 , wherein the treatment resulted in about 85% reduction of nodule count.11 . The method of claim 1 , wherein the treatment resulted in about 90% reduction of nodule count.

12. The method of claim 1 , wherein the treatment resulted in about 95% reduction of nodule count.

13. The method of claim 1 , wherein the treatment inhibited sebum production.

14. The method of claim 1 , wherein the treatment destroyed sebocytes.

15. The method of claim 1 , wherein mean pain score of the patient was from about 5.0 to about 5.6 following the treatment.

16. The method of claim 1 , wherein median pain score of the patient was from about 5.2 to about 5.7 following the treatment.

17. The method of claim 1 , wherein the treatment did not result in hyperpigmentation or hypopigmentation in the patient.

18. The method of claim 1 , wherein the treatment applies to Fitzpatrick skin types.

19. The method of claim 1 , wherein the acne is selected from acne vulgaris, truncal acne, hormonal acne, or acne rosacea.

20. The method of claim 1 , wherein the acne is acne vulgaris.21 . The method of claim 1 , wherein the acne is mild, moderate or severe.

22. The method of claim 1 , wherein the target skin area include forehead, face, lip area, chin, cheeks, and nose.

23. The method of claim 1 , wherein the patient is at least 16 years of age or older.

24. The method of claim 1 , wherein the treatment can further comprise a combination therapy.

25. The method of claim 24, wherein the combination therapy comprises concomitant administration of topical acne medications to the patient in need thereof.

26. The method of claim 25, wherein the topical acne medications comprises retinoids, antibiotics, hormonal agents, benzoyl peroxide (BPO), or any combination thereof.

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