Jeune Aesthetics Announces Efficacy Results for KB301

Jenue Aesthetics, a wholly owned subsidiary of Krystal Biotech, announced positive proof-of-concept efficacy data from the PEARL-1 study (NCT04540900) on KB301.

There are intrinsic and extrinsic factors to skin which leads to the loss of dermal collagen and other proteins. KB301 aims to increase these declining levels of collagen by delivering the human COL3A1 gene, prompting the production of normal type 3 collagen at administration site, according to the press release. KB301 uses Krystal Biotech’s proprietary gene delivery platform to restore protein production and rebuild the underlying extracellular matrix structure.

The phase 1 PEARL-1 study is a dose ranging trial that investigated the safety, efficacy, and tolerability of intradermal injections of KB301 in patients aged 18 to 75. The results from the first cohort, Cohort 1, were presented at the 2021 Society for Investigative Dermatology (SID) Annual Meeting.

In this cohort, 3 different levels of KB301 doses were tested in 7 patients who received 2 intradermal injections into healthy buttock tissue at day 0 and day 30. These treated areas were then compared to undetected of saline injected control tissue on the same patient. Both sites were biopsied at day 2 or day 32. It was found that KB was well-tolerated for COL3A1 supplementation, supporting clinical progression of KB301 for the treatment of aesthetic skin conditions, the release explained.

For the second cohort, Cohort 2, a randomized, double-blind, placebo-controlled clinical trial was conducted evaluating the safety and efficacy of KB301 for the improvement of fine lines and skin texture in the lower and upper cheek and for improvement in skin thickness in the knee.

There were 27 subjects across 2 trial sites included in this cohort that had bilateral treatments conducted. These areas included the neck behind the ear to assess initial safety and on the cheek below and above the zygomatic arch (lower and upper cheek), and around the knee. The patients were randomized 2:1 to receive low dose KB301, or placebo in the upper cheek and knee as multiple micro depot injections over the selected treatment area with a 33G needle. Those who received KB301 in the lower cheek were randomized 2:1 to receive either low dose KB301, high dose KB301, or placebo.

Overall, 4 patients dropped out of the Cohort 2 study. One subject following the initial safety assessment behind the ear, 2 for unspecified reasons, and 1 due to unevenness in face between active and placebo during the study.

Above the Knee Safety and Efficacy Results:

The low dose of KB301 was well-tolerated by patients and the high dose was not administered above the knee. The adverse events (AEs) found were injection site reactions (ISRs) with 100% categorized as mild. The AEs were transitory and dramatically reduced during follow-on injections. There was clinically meaningful efficacy at visit 6, according to Subject Satisfaction Scores, Blinded Independent Reviewer Assessment, and Mean Change in Skin Thickness:

• Subject Satisfaction Scores showed a 21.9% responder rate difference between KB301 and placebo (41.9% for KB301 and 20% for placebo, odds ratio: 2.95);
• Blinded Independent Reviewer Assessment showed a 21.5% response rate difference (54.8% for KB301 and 33.3% for placebo, odds ratio 2.47); and
• The mean change in skin thickness was 1.07mm between KB301 and placebo (KB301: 1.74mm, placebo: 0.67mm).

Lower Cheek (below zygomatic arch) Safety and Efficacy Results:

Both the high and the low dose of KB301 were well-tolerated with the main AE being injection site reactions with 91% categorized as mild and 9% moderate. Efficacy at visit 6 was clinically meaningful across Subject Satisfaction Scores and pictures:

• Subject Satisfaction Scores demonstrated a mean clinical score change of 1.0 between active and placebo for KB301 high dose. The mean score change from baseline to visit 6 was 1.9 for KB301 and 0.9 for placebo;
• Before and after picture evaluations showed clear improvement in both fine lines and skin texture in patients administered with high dose KB301; and
• Blinded independent reviewer assessments using Jeune’s Skin Roughness Score (JASRS) and Fine Lines Score (JAFLS) did not show clinical separation between active and placebo. These scales, developed specifically for this skin area, will be adapted specifically for KB301 by Jeune Aesthetics prior to advancing development.

Upper Cheek (above zygomatic arch) Results:

Low dose KB301 was well-tolerated, and the high dose was not administered. AEs were injection site reactions with 98% mild and 2% moderate. Efficacy at visit 6 was clinically meaningful across Subject Satisfaction Scores and before and after pictures:

• Subject Satisfaction Scores demonstrated a mean clinical score change of 0.6 between active and placebo for KB301 low dose. The mean score change from baseline to visit 6 was 1.3 for KB301 and 0.7 for placebo;
• Before and after picture evaluations showed clear improvement in both fine lines and texture in patients administered with low dose of KB301; and
• Blinded independent reviewer assessments using JASRS and JAFLS did not show clinical separation between active and placebo. These scales, developed specifically for this skin area, will be further developed, validated, and adapted by Jeune Aesthetics specifically for KB301 prior to advancing development.

The patients from the PEARL-1 Cohort 2 trial will be enrolled in a durability trial to look for duration of effect, reduction of the unevenness in placebo treated sites, and for long-term safety monitoring. From the above data, Jeune Aesthetics is currently planning for 2 phase 2a trials to investigate improved skin quality attributes in the lower cheek and to evaluate the potential of improving the aesthetic appearance in a subject’s hand by increasing skin thickness on the back of the subject’s hands. A third phase 2 trial, to evaluate the improvement of skin quality attributes of KB301 in the upper cheek will be initiated following development and validation of Jeune Aesthetics’ scales in the upper cheek, specific to KB301, according to the release.

Reference:

Jeune aesthetics announces positive clinical phase 1 (PEARL-1 Study) efficacy results for kb301, an investigational gene-based treatment designed to address the underlying biology of aging skin. GlobeNewswire News Room. Press release. Published March 22, 2022. Accessed March 29, 2022. https://www.globenewswire.com/news-release/2022/03/22/2407410/0/en/Jeune-Aesthetics-Announces-Positive-Clinical-Phase-1-PEARL-1-Study-Efficacy-Results-for-KB301-an-Investigational-Gene-based-Treatment-Designed-to-Address-the-Underlying-Biology-of-.html