바이오스펙테이터

바이오스펙테이터 Sungmin Kim 기자

Qurient presented the P2a trial results for Q301, a topical treatment for atopic dermatitis currently under Phase 2b, on the international stage, by delivering oral and poster presentations to the 77th Annual Meeting of the American Academy of Dermatology, AAD 2019 held in Washington D.C. from March 1st to 3th. Dr. Alan Fleischer of the Cincinnati Medical School, a medical adviser on Q301, delivered the oral presentation. The AAD, which is the largest dermatological society in the United States, holds an annual meeting, and has about 20,000 members.

A representative of Qurient said, “During this year’s annual meeting of the AAD, big pharmaceutical companies, dermatology pharmacists, and dermatologists showed keen interest in the progress of Phase 2b of Q301, as well as the results of Phase 2a.”

Qurient is currently conducting the P2b clinical trial for Q301 (NCT03571620) on 240 adolescents and adults (aged 12 years or older) with mild to severe symptoms (IGA 2–3) of atopic dermatitis, with the aim of targeting the topical treatment market. The clinical phase 2b is being carried out at 20 sites in North America, and the company serves as a key opinion leader (KOL) in the field of atopy treatment.

There are two aspects that differentiate Q301 from the existing drugs. First, Q301 was developed to have a different mechanism of action, when compared with the currently used drugs that include steroids, antibody drugs, and small molecule compound drugs. These characteristics are important, because doctors prescribe atopic dermatitis drugs with a mechanism of action that is different from the existing drugs, as they do not know exactly what causes atopic dermatitis. In other words, a drug with a different mechanism of action can secure marketability.

Second, the company implemented a strategy to enter the market with a lower production unit price than the existing drugs. Those drugs that have received good responses in the market include ‘Dupixent’, which is IL-14/IL-13 antibody, and ‘Eucrisa’, a PDE4 inhibitor and topical prescription treatment for mild-to-moderate atopic dermatitis. However, they are expensive; Dupixent sells at US $15,000 per syringe, and Eucalyptus at US $650 per 60 g tube. Atopic dermatitis may put a financial burden on patients, because it is not covered by insurance. In fact, when physicians prescribe drugs to patients with atopic dermatitis, they first prescribe cheaper medicines, before they switch to expensive medicines. Qurient, by developing a commercialized formulation of Q301, is likely to be able to lower the drug price to the level of steroid drugs.

Next, let's look at the mechanism by which Q301 acts as a nonsteroidal atopic dermatitis drug. Leukotriene B4 (Leukotriene, LTB4) attracts immune cells to cause itching (pruritus). LTB4 is known as a factor that exacerbates the symptoms of atopic dermatitis. In fact, a high level of LTB4 has been seen in tissues where atopic dermatitis occurs, and if injected into tissues, LTB4 can increase the tissue filtration of neutrophils, a main immune cell that causes inflammation in the atopic lesions. Therefore, by lowering LTB4 levels in the affected tissues with the drug, Qurient was able to resolve both inflammation and itching.

Qurient discovered a clue from Zileuton, an asthma drug developed by Abbot. Zileuton is a 5-a lipoxygenase inhibitor. Lipoxygenase is an enzyme that catalyzes the conversion of arachidonic acid into leukotrienes, a factor that causes inflammation, leading to atopic dermatitis. Zileuton is a substance whose patent has expired. Qurient transformed Zileuton into a cream formulation that can be directly applied to regions where atopic dermatitis occurs. As it can minimize the systemic exposure, the drug can also reduce side effects.

Last year, Qurient completed the patent registration for Q301 with the US and European authorities using a drug repositioning approach, which is the process of finding new uses of existing drugs.

The drug met the primary endpoint in the clinical trial on atopic patients with more severe symptoms than the targeted topical treatment market

In the phase 2a clinical trial, of which the results were announced at the AAD 2019 conference, the safety and efficacy tests were carried out on 52 patients with severe-to-serious symptoms (IGA 3–4) of atopic dermatitis (NCT02426359). The IGA is an indicator of atopic dermatitis symptoms. Because it was difficult to accurately evaluate the drug’s efficacy by conducting tests on patients with modest-to-severe dermatitis symptoms (IGA 2–3), the test was conducted on patients with severe-to-serious dermatitis symptoms.

In the phase 2a clinical trial, the patients applied 1.0 % Q301 cream twice a week or a control drug at the site of atopic dermatitis for 8 weeks. Of the 57 patients who participated in the study, 31 patients applied Q301, while the remaining 26 patients applied the control drug. Both the Q301 group and the control group showed the same median IGA score of 3.2 points.

As the primary endpoint, the number of each group’s patients whose IGA score was 0 (completely removed) or 1 (almost removed) was counted at 8 weeks. As the secondary endpoint, this study measured the Scoring Atopic Dermatitis (SCORAD) and the Eczema Area and Severity Index (EASI), which are indicators of the severity of atopic dermatitis, in addition to the Visual Analog Scale (VAS), an indicator of itching, and the Dermatology Life Quality Index (DLQI), an indicator of the life quality of patients.

Qurient confirmed positive clinical results. According to the results of the intent-to-treat analysis on all patients, the Q301 group showed the IGA cure rate of 29.6 %, compared to the 4.05 % of the control group (p = 0.02). In respect to changes in the EASI90 change, which is the second endpoint, the Q301 group EAS190 change rate was 22.2 %, compared to the 4.0 % of the control group. In other indicators, such as the VAS and EASI, the efficacy of the drug was found to be high.

In respect of the common side effects of the drug, 10.3 % (3/29) patients of the Q301 group complained of itching, while 7.7 % (2/26) patients of the control group had coughs and erythema on the site of application. There was only one case in which all these symptoms appeared at the same time, but they were not serious.

As a result, Qurient said that the phase 2a clinical trial confirmed Q301, a non-steroidal anti-inflammatory drug, to be effective in reducing the symptoms of atopic dermatitis trial.