Takeda Presents Late-Breaking Data from Phase 2b Study of Mezagitamab, Demonstrating Potential to Transform Treatment of Primary Immune Thrombocytopenia

Rhea-AI Summary

Takeda unveiled positive results from its Phase 2b study of mezagitamab (TAK-079) in treating persistent or chronic primary immune thrombocytopenia (ITP). The study showed rapid and sustained platelet increases among patients receiving mezagitamab, with effects persisting for eight weeks post-treatment.

Among patients treated with the 600mg dose, 81.8% achieved complete platelet response, 90.9% achieved clinically meaningful platelet response, and 100% achieved hemostatic platelet response. Adverse events (AEs) were lower in the mezagitamab group compared to placebo. Takeda plans to initiate a Phase 3 trial in the second half of FY2024.

Positive

• Rapid and sustained platelet increases in patients treated with mezagitamab.
• 81.8% of patients achieved complete platelet response at the 600mg dose.
• 90.9% of patients achieved clinically meaningful platelet response at the 600mg dose.
• 100% of patients achieved hemostatic platelet response at the 600mg dose.
• Fewer disease activity-related bleeding AEs in mezagitamab-treated patients (17.9%) compared to placebo (46.2%).
• No new safety signals; favorable safety profile consistent with prior studies.

Negative

• 17.9% of mezagitamab-treated patients experienced Grade >3 TEAEs compared to 23.1% in the placebo group.
• 14.3% of mezagitamab-treated patients faced serious adverse events (SAEs) compared to 7.7% in the placebo group.
• TEAEs led to discontinuation in 14.3% of mezagitamab-treated patients compared to 0% in the placebo group.

Insights

Medical Research Analyst

Takeda's Phase 2b results for mezagitamab in treating primary immune thrombocytopenia (ITP) appear promising. The trial demonstrated long-lasting platelet count increases post-treatment, a key indicator of efficacy since ITP patients suffer from low platelet counts leading to dangerous bleeding risks. By showing sustained efficacy even 8 weeks after the last dose, mezagitamab distinguishes itself from existing treatments.

Moreover, the high percentages of response in various platelet count criteria (up to 100% in hemostatic platelet response) at the highest dose (600mg) indicate robust therapeutic potential. This is particularly significant as it addresses a current gap in effective ITP treatments, potentially setting a new standard for managing the disease.

Regarding safety, the reported rates of adverse events were comparable to or slightly better than the placebo. The lack of new safety signals reinforces the drug's potential for a positive Phase 3 trial outcome. The development of new treatments that patients can tolerate well is critical in chronic conditions like ITP.

Understanding the detailed mechanisms and long-term impacts of mezagitamab will be essential. The transition to a Phase 3 trial reflects confidence in the drug's profile, suggesting significant advancement toward regulatory approval and market introduction.

Market Research Analyst

The announcement of positive Phase 2b results for mezagitamab impacts Takeda's market position and investor sentiment positively. With the plan to initiate a Phase 3 trial in FY2024, Takeda is signaling confidence in its pipeline, specifically targeting the niche market of ITP where there is high unmet need. This positions Takeda as a potential leader in this therapeutic area if the drug receives regulatory approval.

The market for ITP treatments is relatively small but growing due to increased diagnosis rates and longer lifespans of patients. By bringing a potentially best-in-class treatment to market, Takeda could capture significant market share. Furthermore, the favorable safety profile and efficacy data support possible premium pricing and strong adoption by healthcare providers.

Financially, investors should note the potential revenue streams from mezagitamab. Positive Phase 3 outcomes and eventual market entry could lead to substantial revenue growth. However, the development phase includes inherent risks and any setbacks in trial results or regulatory hurdles could negatively impact Takeda’s stock.

Additionally, competition from existing treatments and other pipeline drugs in ITP must be considered. Takeda’s ability to demonstrate superior efficacy and safety will be important in securing a competitive edge.

• Mezagitamab-Treated Patients Showed Rapid and Sustained Increases in Platelet Counts That Persisted 8 Weeks After the Last Dose Through to Week 16¹
  
  
  
  

• Mezagitamab Had a Favorable Safety Profile, with No New Safety Signals¹
  
  
  
  

• Takeda Plans to Initiate Global Phase 3 Trial of Mezagitamab in ITP in the Second Half of FY2024

OSAKA, Japan & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Takeda (TSE:4502/NYSE:TAK) today presented positive results from its Phase 2b, randomized, double-blind, placebo-controlled study evaluating the safety, tolerability and efficacy of mezagitamab (TAK-079) in patients with persistent or chronic primary immune thrombocytopenia (ITP), a rare immune-mediated bleeding disorder. ITP is characterized by the accelerated destruction of platelets in blood, resulting in a decreased platelet count and an increase of bleeding that can be debilitating. These data (Abstract #LB 01.1) were presented at the oral Late-Breakthrough Session at the 32^nd Congress of the International Society on Thrombosis and Haemostasis (ISTH) in Bangkok, Thailand. Takeda plans to initiate a global Phase 3 trial of mezagitamab in patients with ITP in the second half of FY2024.

The TAK-079-1004 trial (NCT04278924) evaluated three different doses of subcutaneous mezagitamab (100mg, 300mg and 600mg) versus placebo, given once weekly for eight weeks in patients with chronic or persistent primary ITP, followed by >8 weeks of safety follow-up. The primary endpoint is the percentage of patients with at least one Grade 3 or higher treatment emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events (AEs) leading to mezagitamab discontinuation.² Secondary endpoints included platelet response, complete platelet response, clinically meaningful platelet response, and hemostatic platelet response.^1,2

The Phase 2b trial results demonstrated that mezagitamab treatment improved platelet response compared to placebo, across all three dose levels of mezagitamab tested. Patients treated with mezagitamab showed rapid and sustained increases in platelet counts (above the 50,000/μL therapeutic threshold)⁴, that persisted eight weeks after the last dose through to Week 16, illustrating the rapid and post-therapy effects of mezagitamab on platelet response.¹

• All the different measures of platelet response evaluated were highest among patients treated with the mezagitamab 600mg dose, specifically 81.8% achieved complete platelet response, 90.9% clinically meaningful platelet response, and 100% hemostatic platelet response.¹
• Fewer mezagitamab-treated patients compared to placebo had ≥1 disease activity-related bleeding AE (17.9% vs 46.2%, respectively).¹

“Despite treatment with currently available therapies, there is still a significant disease burden and need for a disease modifying treatment that people living with ITP can tolerate,” said David Kuter, M.D., D.Phil., a leading expert in ITP and study presenter at the ISTH oral Late-Breakthrough Session. “These Phase 2b trial results are especially encouraging because they show mezagitamab’s favorable efficacy and safety profile – setting the stage for the generation of additional clinical evidence for this anti-CD38 monoclonal antibody with best-in-class potential for efficacy in ITP.”

In this study, mezagitamab had a favorable safety profile in patients with ITP, with no new safety signals and consistent with prior studies of mezagitamab.¹ The rates of TEAEs leading to discontinuation, Grade >3 TEAEs, and SAEs, between the mezagitamab dose groups combined versus placebo were 14.3% versus 0%, 17.9% versus 23.1%, and 14.3% versus 7.7% respectively.¹

“It is a privilege to have these Phase 2b mezagitamab results selected for presentation as a late-breaking abstract at the ISTH Congress,” said Obi Umeh, M.D., M.Sc., Vice President, Franchise Global Program Leader at Takeda. “Based on these results, we plan to initiate a Phase 3 study of mezagitamab in ITP in the second half of FY2024, further underscoring our goal to develop transformative treatments in therapeutic areas with high unmet patient needs.”

About Mezagitamab

Mezagitamab is a fully human immunoglobulin IgG1 monoclonal antibody (mAb), with high affinity for CD38 expressing cells (including plasmablasts, plasma cells, natural killer cells), resulting in their depletion. Therapy with mezagitamab is designed to deliver rapid and sustained improvement in platelet response and to restore platelet counts to functional levels.

Mezagitamab previously received Orphan Drug Designation for the treatment of ITP and Fast Track Designation for treatment of chronic/persistent ITP from the U.S. Food and Drug Administration. Mezagitamab is an investigational compound that has not been approved for use by any regulatory authority.

About the Mezagitamab Phase 2b Trial in ITP

The data presented at the ISTH oral Late-Breakthrough Session are from a pre-specified interim analysis of the Phase 2b trial, a randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, and efficacy of mezagitamab in patients with persistent or chronic primary ITP. The trial had two parts: 25 participants were randomized (1:1:1) to mezagitamab 100mg or 300mg, or placebo in Part A while 16 participants were randomized (2:1) to mezagitamab 600mg or placebo in Part B. Participants received once weekly subcutaneous mezagitamab or placebo for 8 doses, followed by ≥8 weeks of safety follow-up.¹

The primary endpoint is the percentage of patients with TEAEs including Grade 3 or higher events, SAEs and AEs leading to mezagitamab discontinuation. Secondary efficacy endpoints include and are defined as: platelet response (a platelet count ≥50,000/μL and ≥20,000/μL above baseline); complete platelet response (a platelet count ≥100,000/μL); clinically meaningful platelet response (a platelet count ≥20,000/μL above baseline); and hemostatic platelet response (participants with a baseline platelet count of <15,000/μL who achieve a platelet count of ≥30,000/μL and ≥20,000/μL above baseline).² For all secondary efficacy endpoints, platelet counts must be achieved on at least two visits without a dosing period-permitted rescue treatment in the previous four weeks and without any other previous rescue therapy.²

About ITP

ITP is a rare, IgG mediated autoimmune disease caused, in part, by the development of autoantibodies to platelets (and/or megakaryocytes), which are blood components responsible for preventing or stopping bleeding. It is characterized by the accelerated destruction of platelets (with or without impaired production), resulting in a decreased platelet count and an increased risk of bleeding, which can be debilitating (including fatigue and impaired quality of life), and in severe cases may be life-threatening.

The precedent for approval of new drugs in this indication requires that platelet counts be maintained at 50,000/uL or more for a sustained period. Approximately 20 percent of patients with ITP do not achieve a platelet count above 50,000/uL following treatment with available first- and second-line therapies creating significant patient burden and unmet need for a disease modifying treatment that is also tolerable.^3,4

About Takeda

Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit www.takeda.com.

Important Notice

For the purposes of this notice, “press release” means this document, any oral presentation, any question and answer session and any written or oral material discussed or distributed by Takeda Pharmaceutical Company Limited (“Takeda”) regarding this release. This press release (including any oral briefing and any question-and-answer in connection with it) is not intended to, and does not constitute, represent or form part of any offer, invitation or solicitation of any offer to purchase, otherwise acquire, subscribe for, exchange, sell or otherwise dispose of, any securities or the solicitation of any vote or approval in any jurisdiction. No shares or other securities are being offered to the public by means of this press release. No offering of securities shall be made in the United States except pursuant to registration under the U.S. Securities Act of 1933, as amended, or an exemption therefrom. This press release is being given (together with any further information which may be provided to the recipient) on the condition that it is for use by the recipient for information purposes only (and not for the evaluation of any investment, acquisition, disposal or any other transaction). Any failure to comply with these restrictions may constitute a violation of applicable securities laws.

The companies in which Takeda directly and indirectly owns investments are separate entities. In this press release, “Takeda” is sometimes used for convenience where references are made to Takeda and its subsidiaries in general. Likewise, the words “we”, “us” and “our” are also used to refer to subsidiaries in general or to those who work for them. These expressions are also used where no useful purpose is served by identifying the particular company or companies.

Forward-Looking Statements

This press release and any materials distributed in connection with this press release may contain forward-looking statements, beliefs or opinions regarding Takeda’s future business, future position and results of operations, including estimates, forecasts, targets and plans for Takeda. Without limitation, forward-looking statements often include words such as “targets”, “plans”, “believes”, “hopes”, “continues”, “expects”, “aims”, “intends”, “ensures”, “will”, “may”, “should”, “would”, “could”, “anticipates”, “estimates”, “projects” or similar expressions or the negative thereof. These forward-looking statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those expressed or implied by the forward-looking statements: the economic circumstances surrounding Takeda’s global business, including general economic conditions in Japan and the United States; competitive pressures and developments; changes to applicable laws and regulations, including global health care reforms; challenges inherent in new product development, including uncertainty of clinical success and decisions of regulatory authorities and the timing thereof; uncertainty of commercial success for new and existing products; manufacturing difficulties or delays; fluctuations in interest and currency exchange rates; claims or concerns regarding the safety or efficacy of marketed products or product candidates; the impact of health crises, like the novel coronavirus pandemic, on Takeda and its customers and suppliers, including foreign governments in countries in which Takeda operates, or on other facets of its business; the timing and impact of post-merger integration efforts with acquired companies; the ability to divest assets that are not core to Takeda’s operations and the timing of any such divestment(s); and other factors identified in Takeda’s most recent Annual Report on Form 20-F and Takeda’s other reports filed with the U.S. Securities and Exchange Commission, available on Takeda’s website at: https://www.takeda.com/investors/sec-filings-and-security-reports/ or at https://www.sec.gov/. Takeda does not undertake to update any of the forward-looking statements contained in this press release or any other forward-looking statements it may make, except as required by law or stock exchange rule. Past performance is not an indicator of future results and the results or statements of Takeda in this press release may not be indicative of, and are not an estimate, forecast, guarantee or projection of Takeda’s future results.

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.

References:

1. Kuter D, Pulanic D, et al. Safety, tolerability, and efficacy of mezagitamab (TAK-079) in chronic or persistent primary immune thrombocytopenia: Interim results from a phase 2, randomized, double-blind, placebo-controlled study. In: International Society on Thrombosis and Haemostasis (ISTH) Congress; June 22-26, 2024; Bangkok, Thailand. Abstract LB 01.1.
2. https://clinicaltrials.gov/study/NCT04278924. Accessed June 2024.
3. Provan D, Donald A, et al. Blood Advances. 2019;26;3(22):3780-3817.
4. Rodeghiero F. International Journal of Hematology. 2023;117:316–33.

View source version on businesswire.com: https://www.businesswire.com/news/home/20240622463950/en/

Japanese Media

Yuko Yoneyama

yuko.yoneyama@takeda.com

U.S. and International Media

Mark Dole

mark.dole@takeda.com

Source: Takeda Pharmaceutical Company Limited

FAQ

What were the results of Takeda's Phase 2b study of mezagitamab for ITP?

The study showed that mezagitamab led to rapid and sustained increases in platelet counts, with significant responses in patients treated with the 600mg dose.

When did Takeda present the mezagitamab study results?

Takeda presented the results at the 32nd Congress of the International Society on Thrombosis and Haemostasis (ISTH) in Bangkok, Thailand.

What is the next step for Takeda's mezagitamab in treating ITP?

Takeda plans to initiate a global Phase 3 trial of mezagitamab in patients with ITP in the second half of FY2024.

How did mezagitamab perform in terms of adverse events compared to placebo?

Mezagitamab had lower disease activity-related bleeding adverse events (17.9% vs 46.2%), but higher rates of TEAEs leading to discontinuation (14.3% vs 0%) and serious adverse events (14.3% vs 7.7%) compared to placebo.

What were the primary and secondary endpoints of the Phase 2b mezagitamab study?

The primary endpoint was the percentage of patients with Grade 3 or higher treatment-emergent adverse events (TEAEs). Secondary endpoints included various platelet response measures.