InnoCare's TYK2 Allosteric Inhibitor Succeeds in Phase II Trial; Keytruda Shows Positive Perioperative Phase III Results in Head and Neck Cancer; Qilu Pharmaceutical's Riociguat Approved for Market

Oct 10, 2024 17:02 CST Updated 17:02

InnoCare

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Qilu Pharmaceutical

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InnoCare's TYK2 Allosteric Inhibitor Successfully Completes Phase II Study for Psoriasis Treatment, Phase III Clinical Trial Imminent

On October 9, InnoCare announced that its novel Tyrosine Kinase 2 (TYK2) inhibitor ICP-488 reached the primary endpoint in a Phase II clinical trial for the treatment of moderate to severe plaque psoriasis.

ICP-488 is an orally administered, highly selective TYK2 allosteric inhibitor that specifically binds to the TYK2 JH2 domain, blocking the signal transduction of inflammatory cytokines such as IL-23, IL-12, and type I interferons, thereby inhibiting the pathological processes of autoimmune and inflammatory diseases.

This study is a multi-center, randomized, double-blind, placebo-controlled Phase II clinical trial aimed at evaluating the efficacy and safety of ICP-488 in Chinese adult patients with moderate to severe plaque psoriasis. A total of 129 patients were enrolled and randomly assigned to three treatment groups in a 1:1:1 ratio, including a once-daily 6mg group, a once-daily 9mg group, and a placebo group, for continuous administration over 12 weeks. The primary endpoint of the study is the proportion of patients achieving at least a 75% reduction in the Psoriasis Area and Severity Index (PASI 75) score at week 12.

Study results showed that ICP-488 demonstrated significant efficacy and safety in patients receiving the treatment. ICP-488 achieved multiple efficacy endpoints in the 6mg once daily and 9mg once daily dose groups, including Psoriasis Area and Severity Index (PASI) 75, PASI 90, PASI 100 (improvement in PASI score from baseline ≥75%, ≥90%, and ≥100%, respectively), as well as Static Physician's Global Assessment (sPGA) 0/1 (indicating complete or near-complete clearance of skin lesions).

In the once-daily 6mg and 9mg dose groups, the response rates for PASI 75 reached 77.3% and 78.6%, respectively, showing a statistically significant difference compared to 11.6% in the placebo group (p<0.0001). The response rates for PASI 90 in these two dose groups reached 36.4% and 50.0%, respectively, while the placebo group had 0% (p<0.0001); the response rates for PASI 100 reached 11.4% and 11.9%, respectively, while the placebo group had 0% (p<0.05); the response rates for sPGA 0/1 reached 70.5% and 71.4%, respectively, while the placebo group had 9.3% (p<0.0001).

ICP-488 demonstrated good tolerability and safety, with treatment-emergent adverse events (TEAE) and treatment-related adverse events (TRAE) being mild or moderate during the treatment period.

InnoCare will continue to evaluate the efficacy of ICP-488 in treating patients with plaque psoriasis in Phase III studies, while continuing to explore the application of ICP-488 in other autoimmune diseases.

K Drug Perioperative Immunotherapy for Head and Neck Cancer Reaches Primary Endpoint in Phase III Study

On October 8, Merck announced that its anti-PD-1 therapy Keytruda (pembrolizumab) as a perioperative treatment regimen for untreated, resectable stage III or IVA locally advanced head and neck squamous cell carcinoma (LA-HNSCC) patients in the phase III KEYNOTE-689 study met the primary endpoint of event-free survival (EFS).

KEYNOTE-689 is a randomized, open-label Phase III clinical trial (NCT03765918) designed to evaluate the efficacy and safety of pembrolizumab monotherapy as neoadjuvant treatment, followed by continuation with standard radiotherapy (± cisplatin) as adjuvant and maintenance therapy post-surgery, compared with adjuvant radiotherapy alone (± cisplatin) without neoadjuvant treatment, in previously untreated patients with resectable Stage III or IVA LA-HNSCC.

In the pre-specified first interim analysis conducted by the independent Data Monitoring Committee (iDMC), patients receiving perioperative pembrolizumab showed a statistically significant and clinically meaningful improvement in EFS. The study also demonstrated a statistically significant improvement in major pathological response (mPR, a key secondary endpoint) in patients treated with pembrolizumab compared to adjuvant chemoradiotherapy alone. The safety profile of pembrolizumab was consistent with that observed in previously reported studies; no new safety signals were identified.

In patients receiving neoadjuvant pembrolizumab followed by adjuvant and maintenance treatment with standard radiotherapy (± cisplatin) post-surgery, an improvement trend in overall survival (OS) was observed, which is another key secondary endpoint of the study. At the first interim analysis, the OS results for PD-L1 patients with CPS≥10 did not reach statistical significance. Due to the hierarchical relationship of statistical testing, no formal tests were conducted for patients with CPS≥1 or the intention-to-treat (ITT) population. OS will be evaluated at the next interim analysis.

Merck stated that it would announce these research results at the upcoming medical conference and submit them to regulatory authorities.

Qilu Pharmaceutical's Riociguat Approved for Marketing in China

On October 8, the official website of the National Medical Products Administration (NMPA) announced that Qilu Pharmaceutical's Riociguat Tablets have been approved for marketing. This is the first domestically produced generic Riociguat to be approved for marketing in China.

The original research drug Riociguat, developed jointly by Bayer and Merck, is a soluble guanylate cyclase (sGC) activator with a short half-life, requiring three doses per day. Its application in other cardiovascular indications, such as heart failure, is limited. In October 2013, Riociguat was launched in the United States (brand name: Adempas) and entered the Chinese market in September 2017, used for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) and arterial pulmonary hypertension (PAH).

Pulmonary hypertension (PH) is caused by various etiologies and pathogenic mechanisms, with clinical characteristics showing increased pulmonary vascular resistance and pulmonary artery pressure, which can easily lead to right heart failure or even death. PH can be divided into five types based on etiology: Pulmonary arterial hypertension (WHO Group I) can be treated with targeted therapy, WHO Groups II and III can benefit from treating the underlying diseases, and chronic thromboembolic pulmonary hypertension (WHO Group IV) can be treated surgically to remove thrombi or with targeted therapy. Riociguat is the first drug approved for use in both WHO Group I and Group IV pulmonary hypertension.

The compound patent for Riociguat in China expired in 2023, and the PharmaCube database shows that three companies in China have developed generic versions of Riociguat, including Qilu Pharmaceutical, Zhengzhou Deep Blue Sea Biomedical Technology, and Huawei Medicine. Among them, Qilu Pharmaceutical is the fastest, taking the lead in securing the first generic approval.

Editor: Cheng Lin