Takeda 2020: The incredible growing/shrinking pharma

After taking a year to digest Shire, Takeda has been narrowing the company’s focus by divesting non-core products from the portfolio.

By Joshua Slatko • [email protected]

Takeda Pharmaceutical Co.
1-1, Nihonbashi-Honcho 2-Chome
Chuo-ku, Tokyo 103-8668, Japan
Telephone: +81 3 3278-2111
Website: takeda.com

FINANCIAL PERFORMANCE

(All figures are in millions of dollars except EPS and were translated using the Federal Reserve Board’s average rate of exchange in March 2020: ¥107.6673. Takeda’s fiscal year runs from April 1 through March 31. Takeda’s fiscal first quarter runs from April 1 through June 30)

2019

Revenue $30,568

Net income $411

Diluted EPS $0.26

R&D expense $4,573

1Q 2020

Revenue $7,447

Net income $766

Diluted EPS $0.49

R&D expense $992

BEST-SELLING Rx PRODUCTS

2019

Entyvio $3,225

Immunoglobulin $2,774

Vyvanse $2,546

Advate $1,467

Velcade $1,099

Leuprorelin $1,012

Ninlaro $721

Azilva-F $712

Takecab-F $675

Trintellix $657

Takhzyro $634

Elaprase $631

Albumin $624

Dexilant $583

Gattex/Revestive $574

Adynovate $545

Nesina-F $539

1Q 2020

Entyvio $940

Immunoglobulin $790

Vyvanse $613

Advate $313

Leuprorelin $254

Velcade $225

Takhzyro $215

Ninlaro $213

Azilva-F $194

Takecab-F $188

Elaprase $163

Gattex/Revestive $163

Trintellix $157

Nesina-F $144

Adynovate $142

Adcetris $140

Dexilant $126

Outcomes Creativity Index Score: 9
Manny Awards – 2
Cannes Lions – N/A
LIA: Health & Wellness – N/A
Clio Health – N/A
One Show: HW&P – N/A
MM&M Awards – 7
Global Awards – N/A
Creative Floor Awards – N/A

A year after getting a lot bigger with the acquisition of Shire, Takeda is hard at work on getting smaller. Through a series of divestitures – seven so far during the course of 2020 following several others in 2019 – the company has been shedding OTC brands, regional products, branded generics, and pretty much anything else that does not fit into its five key business areas of gastroenterology, rare disease, plasma-derived therapies, oncology, and neuroscience. According to company leaders, Takeda will be using the proceeds from all of this divesting to reduce debt, of which there is plenty. The company’s consolidated bond and loan total was more than $47 billion at the end of Takeda’s 2019 fiscal year in March 2020, the majority of which was related to the Shire transaction; at the end of FY 2017, pre-Shire, Takeda had $9.16 billion in debt. Takeda leaders are targeting a 2.0 net debt to adjusted EBITDA ratio by FY 2023; the company’s net debt to adjusted EBITDA ratio has already improved from 4.7 in March 2019 to 3.8 in March 2020 to 3.7 in June.

“Our transformation into a top 10 global biopharmaceutical company accelerated this year and helped us deliver another set of excellent results,” said Takeda CEO and President Christophe Weber at the end of FY 2019. “We’re fully operating as one Takeda, with growth driven by our five key business areas and a geographic footprint aligned with global market opportunities. Above all, we’re a values-based company that is translating science into life-changing medicines.”

With a year of legacy Shire in the books, Takeda’s top-line revenue for FY 2019 was $30.57 billion, up 56.9 percent compared with the previous (mostly Shire-free) year. Net income, though, declined by 67.3 percent to $411 million, mostly due to restructuring costs and interest expense on bonds and loans related to the Shire integration. In the first quarter of FY 2020, top-line revenue declined 5.6 percent to $7.45 billion, but thanks in part to a one-time net gain arising from the European Commission’s decision to release Takeda from the obligation to divest the legacy Shire compound SHP647, net income rose from $65 million to $766 million and EPS rose 45 cents to 49 cents.

Acquisitions, divestitures, & partnerships

In February, Takeda acquired PvP Biologics Inc. following the conclusion of a Phase I proof-of-mechanism study of the investigational medicine TAK-062 (Kuma062) for the treatment of uncontrolled celiac disease. TAK-062 is a potential best-in-class, highly potent super glutenase – a protein that degrades ingested gluten – that was computationally engineered to treat celiac disease, a serious autoimmune disease where the ingestion of gluten leads to inflammation and damage in the small intestine. The Phase I study investigated TAK-062’s safety and tolerability in both healthy volunteers and people with celiac disease. The ability of TAK-062 to degrade ingested gluten was studied in healthy volunteers. Takeda is planning a Phase IIb efficacy and dose-ranging study of TAK-062 in patients with uncontrolled disease who maintain a gluten-free diet.

Takeda exercised its option to acquire PvP Biologics for a pre-negotiated upfront payment as well as development and regulatory milestones totaling up to $330 million. Takeda and PvP Biologics previously entered into a development and option agreement, under which PvP was responsible for conducting research and development through the Phase I proof-of-mechanism study of TAK-062 in exchange for funding by Takeda related to a pre-defined development plan.

In March, Takeda completed the previously announced sale of a portfolio of select products to Stada Arzneimittel AG for a total of $660 million. The portfolio included about 20 over-the-counter and prescription pharmaceutical products exclusively in Russia, Georgia, and a number of countries from within the Commonwealth of Independent States, which form part of Takeda’s Growth and Emerging Markets Business Unit.

The divested portfolio includes OTC vitamins and food supplements, plus select products within the Cardiovascular, Diabetes, General Medicine, and Respiratory therapeutic areas. Takeda and Stada have also entered into manufacturing and supply agreements under which Takeda will continue to manufacture and supply the products to Stada. The portfolio’s growth is driven by sales of products such as Cardiomagnyl, and other strong regional brands. In addition, about 450 employees supporting the divested assets have transitioned over to Stada.

Also in March, Takeda completed the previously announced sale of a portfolio of select over-the-counter and prescription pharmaceutical assets in a number of Near East, Middle East, and Africa countries within its Growth and Emerging Markets Business Unit (GEM BU) to Acino for a total of more than $200 million.

The transaction included about 30 select prescription pharmaceutical and OTC products. These products will continue to be made available by Takeda in other parts of the world. Close to 270 employees, primarily sales and marketing professionals supporting the portfolio, transitioned to Acino. The parties also entered into multi-year manufacturing and supply agreements, under which Takeda will continue to manufacture the products on behalf of Acino.

Also in March, Takeda agreed to divest a portfolio of select non-core products exclusively in Latin America to Hypera S.A., Brazil’s largest pharmaceutical company with a leading position in branded prescriptions, consumer health, and branded generics, for a total of $825 million. The portfolio includes over-the-counter and prescription pharmaceutical products sold in Brazil, Mexico, Argentina, Colombia, Ecuador, Panama, and Peru, which were part of Takeda’s Growth & Emerging Markets Business Unit.

In April, Takeda agreed to divest a portfolio of select non-core over-the-counter and prescription pharmaceutical products sold in Europe, and two manufacturing sites located in Denmark and Poland, to the Danish pharmaceutical company Orifarm Group for up to about $670 million.

The portfolio divested to Orifarm included a variety of OTC products and food supplements as well as select prescription products in the Respiratory, Anti-inflammatory, Cardiovascular, and Endocrinology therapeutic areas sold predominantly in Denmark, Norway, Belgium, Poland, Finland, Sweden, the Baltics, and Austria. The portfolio generated FY 2018 net sales of about $230 million, driven by strong sales of cough/cold and vitamin OTC brands, as well as the prescription products Warfarin and Levaxin.

In June, Takeda and Neurocrine Biosciences Inc. announced a strategic collaboration to develop and commercialize compounds in Takeda’s early-to-mid-stage psychiatry pipeline. Specifically, Takeda granted an exclusive license to Neurocrine Biosciences for seven pipeline programs, including three clinical-stage assets for schizophrenia, treatment-resistant depression, and anhedonia.

Under the terms of the agreement, Neurocrine Biosciences is responsible for developing and commercializing all pipeline compounds included in the collaboration. Takeda received a total of $120 million in upfront cash. Additionally, Takeda is entitled to development milestones of up to $495 million, commercial milestones of up to $1.4 billion and up to double-digit royalties on net sales. At certain development events, Takeda may elect to opt in or out of a 50:50 profit share on all clinical programs on an asset-by-asset basis. For any asset in which Takeda is participating in a 50:50 profit share arrangement, Takeda is not eligible to receive development or commercial milestones.

Also in June, Takeda agreed to divest a portfolio of select non-core over-the-counter and prescription pharmaceutical products sold exclusively in Asia Pacific to Celltrion Inc., an Incheon, South Korea-based biopharmaceutical company specializing in the research, development and manufacturing of small molecules, biosimilars, and innovative drugs. Takeda received $266 million upfront in cash and may receive up to an additional $12 million in potential milestone payments.

The portfolio divested to Celltrion included a variety of OTC products and pharmaceutical products in the Cardiovascular, Diabetes, and General Medicine therapeutic areas sold predominantly in Australia, Hong Kong, Macau, Malaysia, Philippines, Singapore, South Korea, Taiwan, and Thailand, which are part of Takeda’s Growth and Emerging Markets Business Unit. The portfolio generated FY 2018 net sales of about $140 million, driven by strong sales of the prescription products Nesina and Edarbi.

During August, Takeda agreed to divest Takeda Consumer Healthcare Company Limited, a wholly owned subsidiary focused on the consumer health care market primarily in Japan, to Oscar A-Co KK, a company controlled by funds managed by The Blackstone Group Inc. and its affiliates for a total of ¥242 billion ($2.25 billion). The transaction is expected to close by March 2021.

The portfolio to be divested to Blackstone includes a variety of over-the-counter medicines and health products that generated total revenue of more than ¥60 billion ($557 million) in fiscal year 2019. TCHC’s strong regional brands include Alinamin, its top selling product and Japan’s first vitamin B1 preparation, and Benza, a cold remedy.

Also in August, Takeda and Novavax Inc., a late-stage biotechnology company developing next-generation vaccines for serious infectious diseases, announced a partnership for the development, manufacturing and commercialization of the COVID‑19 vaccine candidate NVX‑CoV2373 in Japan. NVX‑CoV2373 is a stable, prefusion protein made using Novavax recombinant protein nanoparticle technology and includes the company’s proprietary Matrix‑M adjuvant. Takeda will receive funding from the Government of Japan’s Ministry of Health, Labour and Welfare to support the technology transfer, establishment of infrastructure, and scale-up of manufacturing. Takeda anticipates the capacity to manufacture more than 250 million doses of the COVID-19 vaccine per year.

Novavax and Takeda are partnering on manufacturing, clinical development and regulatory activities in Japan. Novavax will license and transfer manufacturing technologies to enable Takeda to manufacture the vaccine antigen and will supply the Matrix-M adjuvant to Takeda. Takeda is responsible for regulatory submission to the MHLW and will produce and distribute NVX CoV2373 in Japan. Novavax will be entitled to receive payments based on the achievement of certain development and commercial milestones, as well as a portion of proceeds from the vaccine.

Also in August, members of the COVID R&D Alliance AbbVie Inc., Amgen Inc., and Takeda announced the first patients enrolled in the I-SPY COVID Trial (Investigation of Serial Studies to Predict Your COVID Therapeutic Response with Biomarker Integration and Adaptive Learning) clinical trial. The I-SPY COVID Trial is evaluating the efficacy of cenicriviroc, a chemokine (CCR2 and CCR5) dual-receptor antagonist, Otezla (apremilast), a PDE4 inhibitor, and Firazyr (icatibant injection), a bradykinin B2 receptor antagonist, in severely ill, hospitalized COVID-19 patients who require high-flow oxygen.

The therapies under investigation were selected based on their potential to impact the immune system response of COVID-19 patients who need respiratory support. About 10-15 percent of patients afflicted by COVID-19 develop acute respiratory distress syndrome, and up to 60 percent of those patients admitted to an ICU require ventilation for an average of two weeks. An estimated half of those patients will not survive. Based on the respective mechanisms of action, Otezla may suppress inflammation resulting from an immune response, Firazyr may ameliorate bradykinin-driven pulmonary edema, and cenicriviroc acts by blocking monocytes trafficking to tissues, features that may help to reduce or mitigate the severity of ARDS response in severely ill COVID-19 patients.

In September, Takeda agreed to divest a portfolio of select non-core prescription pharmaceutical products sold predominantly in Europe and Canada to Cheplapharm. Cheplapharm is a specialty pharmaceutical company with headquarters in Germany and a 25-year history of successfully acquiring, integrating and growing pharmaceutical products. Takeda received an upfront payment of about $562 million.

The portfolio divested to Cheplapharm comprised non-core prescription pharma products in a variety of therapeutic categories sold predominantly in Europe and Canada. This included Cardiovascular/Metabolic and Anti-Inflammatory products along with Calcium. The portfolio generated FY 2019 net sales of about $260 million. While the products included in the sale address key patient needs in these countries, they are outside of Takeda’s five key business areas.

Also in September, Takeda agreed to divest its TachoSil Fibrin Sealant Patch to Corza Health Inc. Takeda will receive €350 million ($392 million) in cash upon closing of the transaction, which is expected by the end of March 2021. TachoSil is a surgical patch trusted by medical professionals globally to deliver safe, fast and reliable bleeding control. Takeda recorded full year net sales for TachoSil of about $160 million in FY 2019.

Under the terms of the agreement, upon close, Corza Health will acquire the assets and licenses that support the development and commercialization of TachoSil, while Takeda will maintain ownership of the manufacturing facility in Linz, Austria. Takeda has entered into a long-term manufacturing services agreement, under which the company will continue to manufacture TachoSil products and supply them to Corza Health. Upon close, about 60 Takeda employees will have the opportunity to transition to Corza Health.

Product performances

The ulcerative colitis and Crohn’s drug Entyvio remained Takeda’s top performer in FY 2019 with sales of $3.23 billion, an improvement of 29 percent. The brand’s market share growth in the United States and Europe was driven by further penetration in the bio-naive segment in UC and CD, combined with increased overall market share. In Japan, Entyvio received an additional indication for CD in the first quarter of FY 2019. First-quarter FY 2020 sales of Entyvio rose another 20.7 percent to $940 million.

In February, Takeda announced results from the Phase III VISIBLE 2 clinical trial evaluating the efficacy and safety of an investigational subcutaneous formulation of the gut-selective biologic Entyvio for use during maintenance therapy in adult patients with moderately to severely active Crohn’s disease. The study evaluated patients who achieved clinical response at week 6 following two doses of open-label vedolizumab intravenous induction therapy at weeks 0 and 2. The results showed that at week 52, significantly more patients on vedolizumab SC compared to placebo were in clinical remission (48.0 percent versus 34.3 percent respectively), meeting the study’s primary endpoint.

In May, the European Commission granted a marketing authorization for the subcutaneous formulation of Entyvio for use as maintenance therapy in adults with moderately to severely active ulcerative colitis or Crohn’s disease. Entyvio SC is available in both a pre-filled syringe and a pre-filled pen. Entyvio was also approved by Chinese regulators in March for adult patients with moderate to severe active ulcerative colitis or Crohn’s disease who have had an inadequate response with, lost response to, or were intolerant to conventional therapies or tumor necrosis factor alpha inhibitors.

The European Commission approval was based on the pivotal Phase III VISIBLE trials which assessed the safety and efficacy of a SC formulation of Entyvio as maintenance therapy in adult patients with moderately to severely active UC or CD who achieved clinical response at week 6 following two doses of open-label vedolizumab intravenous therapy at weeks 0 and 2. Data from an interim analysis of an ongoing, long-term, open-label extension study of patients from VISIBLE 1 and VISIBLE 2 were also considered.

Immunoglobulin, a legacy Shire franchise for the treatment of primary immunodeficiency and multifocal motor neuropathy, generated $2.77 billion in sales for Takeda in FY 2019. In the prior 12-month period with Shire and Takeda, the immunoglobulin franchise generated $2.66 billion in sales. In the first quarter of FY 2020, immunoglobulin sales rose 25.1 percent to $790 million, pushed along by strong demand and growing supply capabilities.

Vyvanse, for treating ADHD, earned $2.55 billion in sales for Takeda in FY 2019, the drug’s first full year in the company’s portfolio after the Shire acquisition. In the prior 12-month period with Shire and Takeda, Vyvanse generated $2.29 billion in sales. In the first quarter of FY 2020, sales of Vyvanse declined 4.1 percent to $613 million, negatively impacted by the appreciation of the yen and the COVID-19 pandemic.

Another legacy Shire product, the hemophilia A treatment Advate, brought in $1.47 billion in sales for Takeda in FY 2019. In the prior 12-month period with Shire and Takeda, Advate generated $1.75 billion in sales. In the first quarter of FY 2020, sales of Advate fell another 21.2 percent to $313 million due to increasing pricing pressure and switches to Adynovate.

Velcade, indicated for the treatment of multiple myeloma, brought in $1.1 billion in sales for Takeda in FY 2019, a decline of 7.5 percent. This was due to the product’s loss of market exclusivity in the previous year. In the first quarter of FY 2020, Velcade sales declined another 23.5 percent to $225 million.

Takeda’s newer multiple myeloma drug Ninlaro enjoyed growth of 24.7 percent in FY 2019, to $721 million. Sales of Ninlaro grew another 25.3 percent in the first quarter of FY 2020, to $213 million. According to company executives, this was due in part to the COVID-19 pandemic, since Ninlaro has a more convenient administration profile than many of its competitors.

In June, Takeda announced positive results from TOURMALINE-MM4, a Phase III, randomized clinical trial evaluating the effect of single-agent oral Ninlaro as a first-line maintenance therapy in adult patients diagnosed with multiple myeloma who had not been treated with stem cell transplantation. The company also presented key insights from the US MM-6 trial, which investigated the effectiveness and safety of an in-class transition to oral Ninlaro in combination with lenalidomide and dexamethasone in newly diagnosed multiple myeloma patients who have previously received a parenteral bortezomib-based triplet induction therapy.

The TOURMALINE-MM4 trial achieved its primary endpoint, with treatment with Ninlaro resulting in a statistically significant and clinically meaningful improvement in progression-free survival versus placebo in adult patients diagnosed with multiple myeloma not treated with stem cell transplantation. This corresponds to a 34 percent reduction in risk of progression or death. Median PFS for patients in the Ninlaro arm was 17.4 months compared to 9.4 months in the placebo arm. The secondary endpoint of overall survival is not yet mature and follow-up is ongoing.

During September, Takeda announced results from the Phase III TOURMALINE-MM2 clinical trial evaluating the addition of Ninlaro to lenalidomide and dexamethasone compared to lenalidomide and dexamethasone plus placebo in newly diagnosed multiple myeloma patients not eligible for autologous stem cell transplant. The study found the addition of Ninlaro to lenalidomide and dexamethasone resulted in a 13.5 month increase in median progression-free survival (35.3 months in the Ninlaro arm, compared to 21.8 months in the placebo arm). The trial did not meet the threshold for statistical significance and the primary endpoint of PFS was not met.

In the prespecified expanded high-risk cytogenetics subgroup, median PFS was 23.8 months in the Ninlaro arm versus 18.0 months in the placebo arm. The rate of CR, a key secondary endpoint in the trial, was 26 percent in the Ninlaro arm versus 14 percent in the placebo arm. After a median follow up of 57.8 months in the Ninlaro arm versus 58.6 months in the placebo arm for OS, the median OS was not reached in either arm. Also, median TTP was longer with the Ninlaro combination versus placebo, at 45.8 months in the Ninlaro arm versus 26.8 months in the placebo arm.

The most impressive performer in Takeda’s portfolio of late has been the legacy Shire product Takhzyro. Sales of the hereditary angioedema drug more than quadrupled last year, from $155 million in FY 2018 (after FDA approval in August 2018 and EU approval in November 2018) with Shire and Takeda to $634 million in FY 2019. In the first quarter of FY 2020 Takhzyro sales rose another 61.2 percent to $216 million.

In June, Takeda announced findings from two new interim analyses of data from the Phase III HELP (Hereditary Angioedema Long-term Prophylaxis) Study Open-label Extension. The analyses suggest that Takhzyro is well-tolerated and can prevent hereditary angioedema attacks over an extended treatment period, with sustained and consistent reduction in monthly attack rate across a range of different patient subgroups.

In the pipeline

In April, FDA granted Breakthrough Therapy Designation for Takeda’s investigational drug mobocertinib (TAK-788) for the treatment of patients with metastatic non-small cell lung cancer with epidermal growth factor receptor exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. There are currently no approved therapies designed to treat this specific form of NSCLC. Mobocertinib is a small-molecule tyrosine kinase inhibitor designed to selectively target EGFR and human EGFR 2 (HER2) exon 20 insertion mutations.

The Breakthrough Therapy Designation was based on the overall response rate and the long-term benefit seen in patients who responded in a Phase I/II study evaluating the safety and efficacy of mobocertinib in patients with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations and have been previously treated with systemic chemotherapy. This signals a potential advancement in addressing the needs of patients for whom no targeted therapies exist and current treatment options provide limited benefit.

In May, FDA approved Alunbrig for adult patients with anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer as detected by an FDA-approved test. This approval expanded Alunbrig’s indication to include the first-line setting. Alunbrig is a potent and selective next-generation tyrosine kinase inhibitor designed to target ALK molecular alterations. The European Commission approved a similar expansion to Alunbrig’s indication the previous month.

FDA’s and the EC’s approvals were based on results from the Phase III ALTA 1L trial, which is evaluating the safety and efficacy of Alunbrig compared to crizotinib in adult patients with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor. After more than two years of follow-up, results from the ALTA 1L trial showed Alunbrig demonstrated superiority over crizotinib, with significant anti-tumor activity observed, especially in patients with baseline brain metastases. Alunbrig reduced the risk of disease progression or death twofold compared with crizotinib, with a 24-month median progression-free survival as assessed by a blinded independent review committee versus 11 months for crizotinib.

Also in May, the European Commission extended the conditional marketing authorization of Adcetris to include treatment of adult patients with previously untreated systemic anaplastic large cell lymphoma, in combination with CHP (cyclophosphamide, doxorubicin, prednisone). Systemic anaplastic large cell lymphoma is a subtype of peripheral T-cell lymphoma.

The EC’s approval was based on the results of the Phase III ECHELON-2 study evaluating Adcetris in combination with CHP to a standard of care, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), in patients with CD30+ PTCL, including the subtype sALCL. The study met the primary endpoint with Adcetris plus CHP demonstrating a statistically significant improvement in progression-free survival in the intent to treat population as assessed by an independent review committee.

Also in May, the European Commission released Takeda from the obligation to divest the pipeline compound SHP647 and certain associated rights, a commitment that was provided by Takeda to secure regulatory clearance of its acquisition of Shire. Takeda will discontinue the current SHP647 clinical trial program, and it will be providing all eligible trial participants with the opportunity to have continued access to SHP647 in a post-trial access study. In addition, Takeda will make SHP647 clinical trial data and biosamples available to the scientific community through the Crohn’s & Colitis Foundation.

Takeda had originally committed to divest SHP647 due to the potential overlap in the area of inflammatory bowel diseases between the company’s marketed product Entyvio and Shire’s SHP647. However, subsequent to the completion of the Shire acquisition, the SHP647 clinical trial program was affected by exceptional circumstances, which caused the EC to conclude that the competition concerns previously identified no longer arise. Accordingly, the EC found that Takeda’s obligation to divest SHP647 was no longer justified and the EC waived the commitment.

Assets and liabilities related to SHP647, which were previously classified as held for sale on Takeda’s consolidated statements of financial position, have ceased to be classified as held for sale as the result of the EC’s decision. Takeda has reversed previously estimated liabilities and will reassess the estimates of the future costs related to SHP647 such as program termination costs, which had a net impact of gain the company’s Operating Profit in the first quarter of FY 2020.

In July, FDA granted Breakthrough Therapy Designation for Takeda’s investigational drug pevonedistat for the treatment of patients with higher-risk myelodysplastic syndromes. Pevonedistat, a first in class NEDD8-activating enzyme inhibitor, could be the first novel treatment for HR-MDS patients in more than a decade, expanding treatment options that have so far been limited to hypomethylating agent (HMA) monotherapy alone.

The Breakthrough Therapy Designation was based on the final analysis of the Pevonedistat-2001 Phase II study, which evaluated pevonedistat plus azacitidine versus azacitidine alone in patients with rare leukemias, including HR-MDS. FDA considered a number of endpoints, including overall survival, event-free survival, complete remission, and transfusion independence, as well as the adverse event profile.

In August, Takeda and Ovid Therapeutics announced positive topline results from the randomized Phase II ELEKTRA study of soticlestat in children with Dravet syndrome or Lennox-Gastaut syndrome. Soticlestat is a potent, highly selective, oral, first-in-class inhibitor of the enzyme cholesterol 24-hydroxylase (CH24H). It is being investigated by Ovid and Takeda for the treatment of rare developmental and epileptic encephalopathies, a group of highly refractory epilepsy syndromes including DS and LGS.

The ELEKTRA study achieved its primary endpoint with high statistical significance, demonstrating a 27.8 percent median reduction from baseline in convulsive seizure and drop seizure frequency compared to a 3.1 percent median increase in patients taking placebo during the 12-week maintenance period. In addition, DS and LGS patients treated with soticlestat demonstrated a 29.8 percent median reduction in convulsive seizure and drop seizure frequency compared to 0.0 percent change in median seizure frequency in patients taking placebo during the full 20-week treatment period (titration plus maintenance) of the ELEKTRA study.

In the ELEKTRA DS cohort, patients treated with soticlestat demonstrated a 33.8 percent median reduction in convulsive seizure frequency compared to a 7.0 percent median increase in patients taking placebo during the full 20-week treatment period of the study (median placebo-adjusted reduction in seizure frequency is 46.0 percent). Based on these data, the companies plan to meet with regulatory authorities to discuss initiation of a Phase III registrational program for soticlestat in patients with DS.

In the ELEKTRA LGS cohort, patients treated with soticlestat demonstrated a 20.6 percent median reduction in drop seizure frequency compared to a 6.0. percent median reduction in patients taking placebo during the full 20-week treatment period of the study (median placebo-adjusted reduction in seizure frequency is 14.8 percent). Additional analyses are being conducted to better understand the potential next steps for the development of soticlestat in this highly heterogenous patient population.