Takeda Receives European Commission Approval for ADZYNMA®▼ (Recombinant ADAMTS13) as the First and Only Recombinant ADAMTS13 Replacement Therapy for Congenital Thrombotic Thrombocytopenic Purpura (cTTP)

Rhea-AI Summary

Takeda has received European Commission approval for ADZYNMA, the first and only recombinant ADAMTS13 replacement therapy for congenital thrombotic thrombocytopenic purpura (cTTP). cTTP is an ultra-rare, potentially fatal blood-clotting disorder with treatment options. The approval is based on the totality of evidence, including results from the first randomized, controlled, open-label, crossover Phase 3 cTTP trial.

Key points:

• ADZYNMA is now approved for treating ADAMTS13 deficiency in children and adult patients with cTTP in the EU
• The Phase 3 trial showed no acute TTP events in patients receiving ADZYNMA prophylactic treatment
• ADZYNMA demonstrated a favorable safety profile compared to plasma-based therapies
• Takeda is also investigating recombinant ADAMTS13 for immune-mediated TTP in an ongoing Phase 2b trial

Positive

• First and only enzyme replacement therapy approved in the EU for cTTP treatment
• No acute TTP events observed in patients receiving ADZYNMA prophylactic treatment in Phase 3 trial
• Favorable safety profile compared to plasma-based therapies
• Potential for expanded use in immune-mediated TTP (ongoing Phase 2b trial)

Negative

• None.

Insights

Medical Research Analyst

The EC approval of ADZYNMA for cTTP treatment is a significant breakthrough in rare disease therapeutics. As the first enzyme replacement therapy for cTTP, it addresses the root cause - ADAMTS13 deficiency. The Phase 3 trial results are promising: no acute TTP events in ADZYNMA-treated patients (n=45) vs. one event with plasma-based therapies (n=46). Moreover, only one subacute TTP event with ADZYNMA compared to seven with plasma-based treatments. The safety profile appears favorable, with common side effects being manageable. This approval could dramatically improve patient outcomes for an ultra-rare disease with a >90% mortality rate if left untreated.

Financial Analyst

Takeda's ADZYNMA approval is a strategic win in the orphan drug market. While it won't impact FY2024 forecasts, it positions Takeda as a leader in rare blood disorders. The ultra-rare nature of cTTP suggests a small but high-value market. Orphan drug designations often come with premium pricing and extended market exclusivity, potentially leading to high profit margins. Moreover, Takeda's ongoing Phase 2b trial for iTTP could expand the drug's market. Investors should note that while rare disease treatments may not generate blockbuster revenues, they often have lower marketing costs and face less competition, contributing positively to long-term profitability.

Market Research Analyst

ADZYNMA's approval marks a paradigm shift in cTTP treatment. As the first-in-class therapy, it has a significant first-mover advantage in an underserved market. The unmet medical need and potential life-saving benefits could drive rapid adoption among specialists. However, the ultra-rare nature of cTTP means a patient pool, which could impact market size. The ongoing iTTP trial is crucial, as expanding indications could substantially increase the target market. Takeda's 70-year legacy in rare blood disorders provides a strong foundation for market penetration. The company's ability to leverage its existing relationships with hematologists and rare disease centers will be key to ADZYNMA's commercial success.

− cTTP is an Ultra-rare, Potentially Fatal Blood-Clotting Disorder with Limited Treatment Options; Untreated, Acute TTP Events Have a Mortality Rate of >90%^1,2

− Approval Based on Totality of Evidence, Including Results from the First Randomized, Controlled, Open-label, Crossover Phase 3 cTTP Trial

OSAKA, Japan & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Takeda (TSE:4502/NYSE:TAK) today announced that the European Commission (EC) approved ADZYNMA^®▼ (recombinant ADAMTS13) for the treatment of ADAMTS13 deficiency in children and adult patients with congenital thrombotic thrombocytopenic purpura (cTTP).³ ADZYNMA is now the first and only enzyme replacement therapy in the European Union (EU) specifically for the treatment of cTTP.^3,4 This approval includes confirmation of orphan medicinal product designation and follows a positive opinion from the Committee for Medicinal Products for Human Use, as announced by the company on May 31, 2024.

cTTP is an ultra-rare, chronic blood clotting disorder caused by a deficiency in the ADAMTS13 enzyme.¹ It is associated with acute events and debilitating chronic symptoms or thrombotic thrombocytopenic purpura (TTP) manifestations, which can include thrombocytopenia, microangiopathic hemolytic anemia, renal manifestations, stroke and abdominal pain.^1,2,5 If left untreated, acute TTP events have a mortality rate of >90%.^1,2

“A century after the scientific discovery of cTTP, significant unmet needs remain for patients who continue to face life-threatening acute events and debilitating chronic symptoms with limited treatment options,” said Ricardo Marek, President, Europe and Canada Business Unit at Takeda. “This approval marks the first treatment specifically indicated to address the root cause of the disease – ADAMTS13 deficiency. Building on our 70-year legacy of innovation in rare blood disorders, we’re proud to offer ADZYNMA to cTTP patients in the EU and remain committed to bringing innovative medicines to rare disease patients with high unmet need.”

The EC approval was supported by the totality of evidence provided by the interim analysis of efficacy, pharmacokinetic, safety and tolerability data from the first randomized, controlled open-label, crossover Phase 3 trial in cTTP, as well as safety and efficacy data from the continuation trial. Data from the Phase 3 trial (NCT03393975) were published in The New England Journal of Medicine in May 2024.

In the Phase 3 trial, patients received 40 IU/kg ADZYNMA IV or plasma-based therapy every other week or weekly, based on regimen at enrollment for months 1-6 (period 1), crossing over to the alternate treatment for months 7-12 (period 2), and all patients received ADZYNMA for months 13-18 (period 3).³

No patient experienced an acute TTP event while receiving ADZYNMA prophylactic treatment (n=45), while there was one acute TTP event in a patient receiving plasma-based therapies (n=46).³ One subacute TTP event was reported in one patient receiving ADZYNMA during the controlled comparison periods 1 and 2, compared to seven subacute TTP events in six patients receiving plasma-based therapies.³ In the continuation phase (period 3), efficacy results – incidence rates of acute and subacute TTP events – were consistent with the results from periods 1 and 2.³

ADZYNMA demonstrated a favorable safety profile compared to plasma-based therapies. The most common adverse reactions (incidence >10%) were headache, diarrhea, dizziness, upper respiratory tract infection, nausea and migraine.³

Takeda is investigating recombinant ADAMTS13 in adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP), the acquired form of TTP, in an ongoing Phase 2b trial (NCT05714969).

This approval does not result in any changes to Takeda’s consolidated forecast for the fiscal year ending March 31, 2025 (FY2024).

About ADZYNMA
ADZYNMA (recombinant ADAMTS13) is the first and only recombinant “A disintegrin and metalloproteinase with thrombospondin motifs 13” (ADAMTS13) enzyme replacement therapy approved for the treatment of ADAMTS13 deficiency in children and adult patients with cTTP. ADZYNMA is also approved by the U.S. Food and Drug Administration (FDA) and by the Japanese Ministry of Health, Labour, and Welfare (MHLW) for the prophylactic and on-demand treatment of patients with cTTP.

ADZYNMA was granted Orphan Drug Designation (ODD) by the U.S. FDA for the treatment and prevention of TTP, including its acquired idiopathic and secondary forms, as well as Fast Track and Rare Pediatric Disease Designation. The U.S. FDA granted Takeda a Rare Pediatric Disease Voucher for the approval of ADZYNMA. ADZYNMA was also granted ODD by the European Medicines Agency (EMA) and Japanese MHLW for the treatment of TTP.

For the full list of side effects and restrictions with ADZYNMA, see the Product Information.

About cTTP
cTTP is an ultra-rare, chronic and debilitating clotting disorder associated with life-threatening acute events and debilitating chronic symptoms, or TTP manifestations.^6,7 Although the exact prevalence of cTTP is unknown, estimates suggest a prevalence of 0.5-2 diagnosed cases/million.⁸ It develops due to deficiency in ADAMTS13, a von Willebrand factor (VWF) cleaving protease, which results in the accumulation of ultra-large VWF multimers in the blood.⁶ The accumulation of ultra-large VWF multimers leads to uncontrolled platelet aggregation and adhesion.^5,7 This can lead to abnormal clotting in the small blood vessels of the body and is associated with microangiopathic hemolytic anemia and low platelet levels (thrombocytopenia).⁵

cTTP has both acute and chronic manifestations (including stroke, renal and cardiovascular disease) and when left untreated, acute TTP events have a mortality rate of >90%.^1,2,5 cTTP can also cause ongoing widespread organ damage and other co-morbidities resulting from an ADAMTS13-deficient state.^2,7,9,10

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.

ADZYNMA is a registered trademark of Takeda Pharmaceuticals International AG.

References:

1. Van Dorland H et al. Haematologica. 2019;104:2107-16.
2. Joly BS et al. Blood. 2017;129(21):2836–2846.
3. ADZYNMA (recombinant ADAMTS13) Summary of Product Characteristics; 2024.
4. Scully M et al. Blood. 2017; 130:2055-63.
5. Chiasakul T and Cuker A. Am Soc Hematol. 2018;2018(1):530–538.
6. Alwan F et al. Blood. 2019;133:1644-51.
7. Kremer Hovinga JA et al. Nat Rev Dis Primers. 2017;3:17020.
8. Kremer Hovinga JA and George JN. Hereditary Thrombotic Thrombocytopenic Purpura. N Engl J Med. 2019;381(17):1653-1662.
9. Zheng XL et al. J Thromb Haemost. 2020;18(10):2486-95.
10. Sukumar S et al. J Clin Med. 2021;10:536.

View source version on businesswire.com: https://www.businesswire.com/news/home/20240806343138/en/

Japanese Media

Jun Saito

jun.saito@takeda.com

U.S. and International Media

Megan Ostrower

megan.ostrower@takeda.com

Source: Takeda Pharmaceutical Company Limited

FAQ

What is ADZYNMA and what has Takeda (TAK) received approval for?

ADZYNMA is a recombinant ADAMTS13 replacement therapy. Takeda (TAK) has received European Commission approval for ADZYNMA as the first and only treatment for congenital thrombotic thrombocytopenic purpura (cTTP) in the European Union.

What were the key results from the Phase 3 trial of ADZYNMA for cTTP?

In the Phase 3 trial, no patients experienced acute TTP events while receiving ADZYNMA prophylactic treatment. Only one subacute TTP event was reported in a patient receiving ADZYNMA, compared to seven subacute TTP events in six patients receiving plasma-based therapies.

What are the most common side effects of ADZYNMA reported in the clinical trials?

The most common adverse reactions (incidence >10%) reported for ADZYNMA were headache, diarrhea, dizziness, upper respiratory tract infection, nausea, and migraine.

Is Takeda (TAK) investigating ADZYNMA for other conditions besides cTTP?

Yes, Takeda (TAK) is currently investigating recombinant ADAMTS13 in adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) in an ongoing Phase 2b trial (NCT05714969).