HMPL-004 / Hutchmed - LARVOL DELTA

Perspectives of international multi-center clinical trials on traditional Chinese herbal medicine. (PubMed, Front Pharmacol) - "Since, a variety of drug products in China have been approved for marketing in other countries, and approximately 10 products have submitted the IND application to FDA of United States, of which various Chinese herbal preparations such as compound Danshen dripping pills, Xingling granules, and HMPL-004 have been approved to be investigated in phase III clinical trials...In addition, it is also required to further improve the evaluation techniques and methods that not only meet the international standards but also meet the characteristics of TCHM. Furthermore, we should also focus on the TCHM specific clinical values and scientific reports."

Journal • Review • Infectious Disease • Novel Coronavirus Disease

Andrographis paniculata extract (HMPL-004) for active ulcerative colitis (Am J Gastroenterol) - P2, N=224; NCT00659802; 45% of pts receiving HMPL-004 1,200mg (p=0.5924) & 60% of pts receiving 1,800mg HMPL-004 (p=0.0183) daily, were in clinical response at wk 8 vs. 40% of pts receiving PBO; 34% of pts receiving HMPL-004 1,200mg (p=0.2582) & 38% of pts receiving 1,800mg (p=0.1011) daily dose were in clinical remission at wk 8 vs. 25% pts receiving PBO

P2 data • Immunology • Inflammatory Bowel Disease

A phase III trial of HMPL-004 in patients with mild to moderate active ulcerative colitis (clinicaltrials.gov) - P3, N=420; Sponsor: Hutchison Medipharma Limited; Not yet recruiting; New P3 trial; Pipeline shift: P2 -> P3.

New P3 trial • Phase shift • Immunology • Inflammatory Bowel Disease

Hutchison China MediTech: FY 2014 Results (Hutchison China MediTech) - "Interim analysis on HMPL-004 NATRUL-3 Phase III study showed, despite a solid safety profile, no overall efficacy benefit was observed so the study was terminated. Subsequent sub-group analysis shows a strong trend to efficacy in remission in the high-dose 2,400mg/day treatment arm among 5-ASA refractory patients. Nestlé Health Science and Chi-Med are currently reviewing data. Decision on next steps to be made in 2015"

Trial termination • Immunology • Inflammatory Bowel Disease

Hutchison China MediTech: Q2 2014 Results (Hutchison China MediTech) - "HMPL-004"; "Ulcerative Colitis Phase III Interim Analysis"; "Strong HMPL-004 Phase IIb data in UC...but high placebo,(historically common in IBD)"; "Baseline patient: 7-9 Modified Mayo Score (out of 12): 3+ stools/day (last 5-7 days), Blood w/stool. Serious abnormalities"; "Remission patient: 0-2 Modified Mayo Score (out of 12): Normal stools/day (last 5-7 days), No blood seen. Mild symptoms" 

P2 data • Immunology • Inflammatory Bowel Disease

Hutchison China MediTech: Q2 2014 Results (Hutchison China MediTech) - Anticipated launch for ulcerative colitis in 2017

Anticipated launch • Inflammatory Bowel Disease

HMPL-004 NATRUL-3 interim analysis result (Hutchison China MediTech Press release) - P3, N=420; NATRUL-3 (NCT01805791); "Nutrition Science Partners Limited (“NSP”)...announces that a planned interim analysis was conducted on NATRUL-3...An independent Data Safety and Monitoring Committee (“DSMC”) evaluated the unblinded data of two doses of HMPL-004 vs. placebo, and has recommended that NSP terminate the study. No meaningful safety signals or risks for patients were identified, and further analysis and review of the data will be conducted. The NSP Board will continue to evaluate the potential opportunities of HMPL-004 in new indication areas and alternative regulatory pathways."

Anticipated new indication • P3 data • Trial termination • Immunology • Inflammatory Bowel Disease

HMPL-004 sales projection: $300M peak per year in 2022; HMPL-004 launch estimate: After 2016 (Charles Stanley and Co Ltd) - A subscription to Thomson One is required to gain full access to Report 20065152

Financial analyst: Commercial • Immunology • Inflammatory Bowel Disease

Hutchison China MediTech Limited (“Chi-Med”) (AIM: HCM) interim results for the six months ended 30 June 2014 (Hutchison China MediTech Press release) - P3, N=460, NATRUL-4 (NCT01882764); Sponsor: Hutchison Medipharma; P3, N=420; NATRUL-3 (NCT01805791); Anticipated P3 interim data for NATRUL-3 study in mid-August; "The HMPL-004 clinical programme is a major investment for NSP, with spending of $11.4 million in the first half of 2014..."

Anticipated P3 data • Commercial • Immunology • Inflammatory Bowel Disease

HMPL004-6599 Phase I Dose-escalating Study (clinicaltrials.gov) - P1; N=32; Terminated; Sponsor: Nutrition Science Partners Limited; N=56 ➔ 32; Recruiting ➔ Terminated; Sponsor decision

Clinical • Enrollment change • Trial termination

In the event of "Chinese medicine going to sea", Chinese medicine companies such as Tasly and Kanglaite may have deviated [Google Translation] (Eastmoney.com) - "According to the FDA clinical trial website...three Chinese medicine preparations were allowed to enter the final phase III clinical trial phase, namely...HMPL-004 of Hutchison Whampoa....Clinical trials Andrographis preparations HMPL-004 due to the ineffectiveness of interim results have already been terminated....The above mentioned andrographis preparation HMPL-004 of Hutchison Whampoa was discontinued because of the results of the interim ineffectiveness analysis....At the time of the interim analysis, endpoint events may have occurred before randomized trials have shown efficacy."

Discontinued