HUTCHMED Initiates Registration Stage of the ESLIM-02 Phase II/III Trial of Sovleplenib for Warm Antibody Autoimmune Hemolytic Anemia in China
HUTCHMED initiates Phase II/III clinical trial for sovleplenib in wAIHA patients in China, following positive Phase II data. The trial aims to confirm safety and efficacy, with the first patient dosed on March 20, 2024.
The initiation of a Phase II/III clinical trial for sovleplenib by HUTCHMED marks a significant milestone in the development of treatments for warm antibody autoimmune hemolytic anemia (wAIHA), a condition with currently limited therapeutic options. The progression to a registration-stage trial reflects confidence in the preliminary data and suggests a potential for the drug to meet an unmet medical need, which could translate into a substantial market opportunity. Given the rarity of wAIHA, the treatment's success could also pave the way for sovleplenib's application in other autoimmune diseases, potentially expanding its commercial viability.
From a safety and efficacy standpoint, the primary endpoint—durable hemoglobin response—is a direct measure of the drug's impact on the disease's clinical manifestation. A positive outcome here would not only be promising for patient health outcomes but could also strengthen investor confidence in HUTCHMED's pipeline. However, investors should consider the inherent risks of clinical trials, including the possibility of adverse effects or failure to meet the primary endpoint, which could affect the company's stock performance.
Within the healthcare sector, the advancement of sovleplenib into late-stage clinical trials is a noteworthy event, particularly for a specialized area like wAIHA. The disease's low prevalence means that the potential patient population is small, which could limit the drug's revenue potential. However, orphan drugs for rare diseases often benefit from regulatory incentives, such as extended market exclusivity and tax credits, which can enhance profitability.
The collaboration with notable Chinese medical institutions and principal investigators adds credibility to the study and could facilitate faster patient recruitment and trial execution. The involvement of the China National Medical Products Administration (NMPA) in the consultation process also indicates regulatory engagement, which could streamline the NDA filing and approval process if the trial data is positive. It's important for stakeholders to monitor patient enrollment rates and interim data releases, as these can provide early indications of the trial's progress and potential outcome.
For investors, the initiation of the registration stage of the Phase II/III clinical trial for sovleplenib represents a key inflection point in HUTCHMED's valuation. The trial's success could lead to a new drug application, which would be a major catalyst for the company's stock. The market often responds favorably to positive clinical trial outcomes, especially for drugs targeting diseases with high unmet needs. Conversely, delays or negative results could pose significant risks to the company's projected earnings and growth trajectory.
Given the specifics of the trial, such as the randomized, double-blind, placebo-controlled design, the results will have a high level of scientific validity, which is important for regulatory approval and market acceptance. Investors should assess the potential impact of sovleplenib on HUTCHMED's revenue, considering both the size of the wAIHA market and the possibility of premium pricing for orphan drugs. Additionally, the strategic implications of the drug's success for HUTCHMED's overall pipeline and future R&D directions should be considered in investment analyses.
03/21/2024 - 08:00 PM
HONG KONG and SHANGHAI, China and FLORHAM PARK, N.J., March 22, 2024 (GLOBE NEWSWIRE) -- HUTCHMED (China) Limited (“HUTCHMED ”) (Nasdaq/AIM:HCM; HKEX:13) today announces that it has initiated the registration stage of the Phase II/III clinical trial of sovleplenib in adult patients with warm antibody autoimmune hemolytic anemia (“wAIHA”) in China.
This follows positive data from the proof-of-concept Phase II stage of the trial and subsequent consultation with the China National Medical Products Administration (“NMPA”). If positive, the data from the trial may be used to support a future New Drug Application (“NDA”) filing. wAIHA is an autoimmune disorder that can lead to anemia and has limited treatment options. The first Phase III patient received their initial dose on March 20, 2024.
ESLIM-02 is a randomized, double blind, placebo-controlled Phase II/III clinical trial. The objective of the registration stage of the study is to confirm the safety and efficacy of sovleplenib in adult patients with wAIHA. The primary endpoint for the study is the proportion of patients who achieve a durable hemoglobin (Hb) response by Week 24. 21 patients have been enrolled in the study so far and approximately 90 more patients are expected to be enrolled to this registration stage. The lead principal investigators are Dr. Fengkui Zhang of Chinese Academy of Medical Sciences Blood Diseases Hospital, Dr. Bing Han of Chinese Academy of Medical Sciences Peking Union Medical College Hospital and Dr. Liansheng Zhang of Lanzhou University Second Hospital. Additional details may be found at clinicaltrials.gov , using identifier NCT05535933 .
About Sovleplenib
Sovleplenib is a novel, investigational, selective small molecule inhibitor for oral administration targeting the spleen tyrosine kinase, also known as Syk. Syk is a major component in B-cell receptor and Fc receptor signaling and is an established target for the treatment of multiple subtypes of B-cell lymphomas and autoimmune disorders. HUTCHMED currently retains all rights to sovleplenib worldwide.
In addition to wAIHA, sovleplenib is also being studied in immune thrombocytopenia (“ITP”). ESLIM-01 (NCT05029635 ) is a randomized, double-blinded, placebo-controlled Phase III trial in China of sovleplenib in patients with primary ITP that met all its endpoints . ITP is an autoimmune disorder that can lead to increased risk of bleeding. The NMPA granted Breakthrough Therapy designation for this indication and accepted the New Drug Application (NDA) for review with Priority Review in January 2024. A dose-finding study in the U.S. is in planning (NCT06291415 ).
About wAIHA and Syk
AIHA is an autoimmune disorder characterized by the destruction of red blood cells (“RBCs”) due to the production of antibodies against RBC. The incidence of AIHA is estimated to be 0.8-3.0/100,000 adults per year with an estimated prevalence of 17 per 100,000 adults and a death rate of 8% -11% .1 , 2 wAIHA is the most common form of the autoimmune hemolytic diseases,3 accounting for about 75-80% of all adult AIHA cases.4
The accelerated clearance of antibody-coated RBCs by immunoglobulin Fc receptor (“FcR”) bearing macrophages is thought to be the pathogenic mechanism in wAIHA.5 Activation of the FcR is associated with a signaling subunit, FcRγ, whose phosphorylation subsequent to receptor binding results in the recruitment and activation of Syk.6 Activated Syk mediates downstream signaling of the activated FcRs in phagocytic cells, resulting in phagocytosis of RBCs.7 In addition, activation of Syk through the B-cell receptor mediates activation and differentiation of B-lymphocytes into antibody secreting plasma cells.8 Therefore, inhibition of Syk may have potential effects in the treatment of wAIHA through inhibition of phagocytosis and reduction of antibody production.
About HUTCHMED
HUTCHMED (Nasdaq/AIM: HCM; HKEX: 13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three oncology medicines now marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch-med.com or follow us on LinkedIn .
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of sovleplenib for the treatment of patients with wAIHA and the further development of sovleplenib in this and other indications. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the timing and outcome of clinical studies and the sufficiency of clinical data to support an NDA submission of sovleplenib for the treatment of patients with wAIHA or other indications in China or other jurisdictions, its potential to gain approvals from regulatory authorities on an expedited basis or at all, the efficacy and safety profile of sovleplenib, HUTCHMED’s ability to fund, implement and complete its further clinical development and commercialization plans for sovleplenib and the timing of these events. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, The Stock Exchange of Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.
Medical Information
This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.
CONTACTS
Investor Enquiries +852 2121 8200 / ir@hutch-med.com Media Enquiries Ben Atwell / Alex Shaw, FTI Consulting +44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) / HUTCHMED@fticonsulting.com Zhou Yi, Brunswick +852 9783 6894 (Mobile) / HUTCHMED@brunswickgroup.com Nominated Advisor Atholl Tweedie / Freddy Crossley / Daphne Zhang, Panmure Gordon +44 (20) 7886 2500
_____________________REFERENCES
1 Eaton WW, Rose NR, Kalaydjian A, Pedersen MG, Mortensen PB. Epidemiology of autoimmune diseases in Denmark. J Autoimmun. 2007; 29 (1):1-9. doi: 10.1016/j.jaut.2007.05.002. 2 Roumier M, Loustau V, Guillaud C, et al. Characteristics and outcome of warm autoimmune hemolytic anemia in adults: new insights based on a single-center experience with 60 patients. Am J Hematol. 2014; 89 (9):E150-5. doi: 10.1002/ajh.23767. 3 Cotran Ramzi S, Kumar Vinay, Fausto Nelson, Nelso Fausto, Robbins Stanley L, Abbas Abul K. Robbins and Cotran pathologic basis of disease. St. Louis, Mo: Elsevier Saunders; 2005. p. 637. 4 Gehrs BC, Friedberg RC. Autoimmune haemolytic anemia. Am J Hematol. 2002; 69:258–271. doi: 10.1002/ajh.10062. 5 Barros MM, Blajchman MA, Bordin JO. Warm autoimmune hemolytic anemia: recent progress in understanding the immunobiology and the treatment. Transfus Med Rev. 2010; 24(3):195‐210. doi: 10.1016/j.tmrv.2010.03.002. 6 Braselmann S, Taylor V, Zhao H, et al. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex‐mediated inflammation. J Pharmacol Exp Ther. 2006; 319(3):998‐1008. doi: 10.1124/jpet.106.109058. 7 Barcellini W, Fattizzo B, Zaninoni A. Current and emerging treatment options for autoimmune hemolytic anemia. Expert Rev Clin Immunol. 2018; 14(10):857‐872. doi: 10.1080/1744666x.2018.1521722. 8 Davidzohn N, Biram A, Stoler‐Barak L, Grenov A, Dassa B, Shulman Z. SYK degradation restrains plasma cell formation and promotes zonal transitions in germinal centers. J Exp Med. 2020; 217(3):e20191043. doi: 10.1084/jem.20191043.
What is HUTCHMED initiating in China?
HUTCHMED is initiating the registration stage of the Phase II/III clinical trial for sovleplenib in adult patients with wAIHA in China.
What is the primary endpoint of the study?
The primary endpoint of the study is the proportion of patients who achieve a durable hemoglobin (Hb) response by Week 24.
Who are the lead principal investigators for the trial?
The lead principal investigators are Dr. Fengkui Zhang, Dr. Bing Han, and Dr. Liansheng Zhang.
What is the identifier for additional details on the trial?
Additional details may be found at clinicaltrials.gov, using identifier NCT05535933.
