Newsroom

# Newsroom

**OSAKA, Japan, September 29, 2023** – Takeda ([TSE:4502/NYSE:TAK](https://www.takeda.com/investors/)) (“Takeda”) today announced it has submitted a New Drug Application (NDA) to the Ministry of Health, Labour and Welfare (MHLW) in Japan for fruquintinib, a selective inhibitor of vascular endothelial growth factor receptor (VEGFR)1, 2 and 3 for the treatment of previously treated metastatic colorectal cancer.

The NDA for fruquintinib is based on the Phase 3 FRESCO-2 global clinical trial conducted in the U.S., Europe, Japan and Australia, as well as the Phase 3 FRESCO clinical trial conducted in China. The FRESCO-2 and FRESCO clinical trials compared fruquintinib plus best supportive care (BSC) with placebo plus BSC in patients with previously treated metastatic CRC. Both trials demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), and progression-free survival (PFS). Fruquintinib was shown to be generally well tolerated by patients.

“Colorectal cancer has the highest incidence and second highest mortality rate among both men and women in Japan1. With these rates consistently increasing each year, the necessity for new treatment options becomes even more evident,” stated Awny Farajallah, M.D., head of Global Medical Affairs Oncology at Takeda. “Following submissions in the U.S and Europe, we are delighted to have submitted the new drug application for fruquintinib to the MHLW, moving one step closer to potentially offering this innovative therapy to patients with advanced disease in Japan.”

The U.S Food and Drug Administration (FDA) granted Priority Review to the new drug application for fruquintinib in May 2023 and assigned a Prescription Drug User Fee Act (PDUFA) goal date of November 30, 2023. A Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) was validated in June 2023.

Takeda has the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside of China. Fruquintinib is developed and marketed in China by HUTCHMED.

## About Fruquintinib

Fruquintinib is a selective oral inhibitor of VEGFR1/2/3. VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for high drug exposure, sustained target inhibition, and flexibility for the potential use as part of combination therapy. So far, fruquintinib has been shown to be generally well tolerated in patients.

## About FRESCO-2

The FRESCO-2 study is a multi-regional clinical trial conducted in the U.S., Europe, Japan and Australia investigating fruquintinib plus BSC vs placebo plus BSC in patients with previously treated metastatic CRC. As [previously disclosed](https://www.hutch-med.com/fresco-2-met-primary-endpoint/), the 691-patient study met its primary endpoint of OS in patients with metastatic CRC who had progressed on standard chemotherapy and relevant biologic agents and who had progressed on, or were intolerant to, TAS-102 and/or regorafenib. In addition to OS, a statistically significant improvement in PFS, a key secondary endpoint, was observed. Fruquintinib has been generally well tolerated in patients to date. Results2,3 from the study were [presented](https://www.hutch-med.com/fruquintinib-fresco-2-data-summary-esmo-2022/) at ESMO in September 2022 and subsequently [published](https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23\)00772-9/fulltext) in The Lancet. Additional details of the study may be found at clinicaltrials.gov, using identifier [NCT04322539](https://classic.clinicaltrials.gov/ct2/show/NCT04322539).

## About CRC

CRC is a cancer that starts in either the colon or rectum. According to the International Agency for Research on Cancer, CRC is the third most prevalent cancer worldwide, associated with more than 935,000 deaths in 2020.4 In the U.S., it is estimated that 153,000 patients will be diagnosed with CRC and 53,000 deaths from the disease will occur in 2023.5 In Europe, CRC was the second most common cancer in 2020 with approximately 520,000 new cases and 245,000 deaths. In Japan, CRC was the most common cancer with an estimated 156,000 new cases and 68,000 deaths in 2019.1 Although early-stage CRC can be surgically resected, metastatic CRC remains an area of high unmet need with poor outcomes and limited treatment options.

## 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 <https://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 [www.sec.gov](http://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. Cancer Statistics. Cancer Information Service, National Cancer Center, Japan (Vital Statistics of Japan, Ministry of Health, Labour and Welfare)：<https://ganjoho.jp/public/qa_links/report/statistics/2023_jp.html>

2. Dasari NA, et al. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study [published online ahead of print, 2023 Jun 15]. Lancet. 2023. DOI: 10.1016/S0140-6736(23)00772-9.

3. Dasari NA, et al. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study [published online ahead of print, 2023 Jun 15]. Lancet. 2023. DOI: 10.1016/S0140-6736(23)00772-9.

4. Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660.

5. Siegel RL, et al. Colorectal cancer statistics, 2023 [published online ahead of print, 2023 Mar 1]. CA Cancer J Clin. 2023; 73(3):233-254. doi:10.3322/caac.21772.

### Media Contact:

Toshiyuki Ikeuchi

<toshiyuki.ikeuchi@takeda.com>

＋80‐2419‐1585

Submission of a NDA to the MHLW in Japan for Fruquintinib, a selective inhibitor of VEGFR 1, 2 and 3

Takeda Submits New Drug Application for Fruquintinib for Previously Treated Metastatic Colorectal Cancer in Japan

ADCETRIS receives positive CHMP opinion for extension of marketing authorization in combination therapy for previously untreated Hodgkin lymphoma patients.

Takeda Receives Positive CHMP Opinion for ADCETRIS® (brentuximab vedotin) for the Treatment of Adult Patients with Previously Untreated CD30+ Stage III Hodgkin Lymphoma in Combination with AVD

Publication shows FRESCO-2 demonstrated treatment with fruquintinib reduced the risk of death by 34% in previously treated metastatic colorectal cancer (0.66 HR)

Takeda and HUTCHMED Announce Publication of Phase 3 FRESCO-2 Results in The Lancet

***— Application Includes Data from Phase 3 FRESCO-2 and FRESCO Clinical Trials, which Demonstrated Superiority of Fruquintinib Plus Best Supportive Care (BSC) vs. Placebo plus BSC for Adult Patients with Previously Treated Metastatic Colorectal Cancer***

**OSAKA, Japan, CAMBRIDGE, Massachusetts, HONG KONG, SHANGHAI and FLORHAM PARK, New Jersey, June 15, 2023 –** Takeda [(TSE:4502/NYSE:TAK)](https://www.takeda.com/investors/overview/) and HUTCHMED (China) Limited (Nasdaq/AIM: HCM, HKEX: 13) (HUTCHMED) today announced that the European Medicines Agency (EMA) has validated and accepted for regulatory review the marketing authorization application (MAA) for fruquintinib, a highly selective and potent inhibitor of vascular endothelial growth factor receptors (VEGFR) -1, -2 and -3 for the treatment of adult patients with previously treated metastatic colorectal cancer (CRC). If approved, fruquintinib will be the first and only highly selective inhibitor of all three VEGF receptors approved in the European Union (EU) for previously treated metastatic CRC.1,2

"European patients with metastatic colorectal cancer have not benefitted from a treatment advancement in over a decade,” said Awny Farajallah, M.D., head of Global Medical Affairs Oncology at Takeda. “We are thrilled to have submitted the marketing authorization application to the EMA, bringing us one step closer to potentially offering this innovative therapy to patients with advanced disease. We believe fruquintinib has the potential to address the longstanding unmet need for patients with previously treated metastatic colorectal cancer regardless of their biomarker status, and we look forward to working with the regulators throughout the process.”

The MAA for fruquintinib includes results from the Phase 3 FRESCO-2 trial along with data from the Phase 3 FRESCO trial conducted in China. FRESCO-2 is a global Phase 3 multi-regional clinical trial (MRCT) conducted in the U.S., Europe, Japan and Australia investigating fruquintinib plus best supportive care (BSC) vs placebo plus BSC in patients with previously treated metastatic CRC. The FRESCO-2 trial met its primary and key secondary endpoints, showing a significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS), respectively. Fruquintinib has been generally well tolerated in patients to date.

“Based on fruquintinib’s clinical profile to date, we are optimistic about its potential as a choice for patients and physicians in the EU who find treatment options to be limited for previously treated metastatic colorectal cancer,” said Dr. Michael Shi, Head of R&D and Chief Medical Officer, HUTCHMED. "We believe the EMA validation of the marketing authorization application for fruquintinib represents an exciting initial step toward advancing treatment for patients in Europe and look forward to supporting Takeda as it pursues this goal.”

The validation follows the acceptance by the U.S Food and Drug Administration (FDA) of a new drug application (NDA), [announced ](https://www.takedaoncology.com/news/news-releases/takeda-and-hutchmed-announce-new-drug-application-for-fruquintinib-for-treatment-of-previously-treated-metastatic-colorectal-cancer-granted-priority-review/)on May 25, 2023, which was granted Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) goal date of November 30, 2023. Submission of an NDA to the Japan Pharmaceuticals and Medical Devices Agency (PMDA) is also planned in 2023. Fruquintinib is currently approved in China under the brand name ELUNATE®. Approval in China was based on the results of the FRESCO study, a Phase 3 pivotal registration trial of fruquintinib in 416 patients with metastatic CRC in China, published in *The Journal of the American Medical Association*, JAMA, in June 2018 ([NCT02314819](https://clinicaltrials.gov/ct2/show/NCT02314819)).3 In March 2023, HUTCHMED and Takeda [closed ](https://www.hutch-med.com/closing-of-fruquintinib-license-to-takeda-outside-china/)an exclusive licensing agreement to further the global development, commercialization and manufacture of fruquintinib outside of China.

## About Fruquintinib

Fruquintinib is a highly selective and potent oral inhibitor of VEGFR -1, -2 and -3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to improve kinase selectivity with the intention of minimizing off-target toxicities, improving tolerability and providing more consistent target coverage. Fruquintinib has been generally well tolerated in patients to date and is being investigated in combinations with other anti-cancer therapies.

## About FRESCO-2

The FRESCO-2 study is a multi-regional clinical trial conducted in the U.S., Europe, Japan and Australia investigating fruquintinib plus BSC vs placebo plus BSC in patients with previously treated metastatic CRC. As [ previously disclosed](https://www.hutch-med.com/fresco-2-met-primary-endpoint/), the 691-patient study met its primary endpoint of OS in patients with metastatic CRC who had progressed on standard chemotherapy and relevant biologic agents and who had progressed on, or were intolerant to, TAS-102 and/or regorafenib. In addition to OS, a statistically significant improvement in PFS, a key secondary endpoint, was observed. Fruquintinib has been generally well tolerated in patients to date. Summary results were initially presented at the European Society for Medical Oncology (ESMO) Congress in September 2022.4 Additional details of the study may be found at clinicaltrials.gov, using identifier [ NCT04322539](https://clinicaltrials.gov/ct2/show/NCT04322539).

## About CRC

CRC is a cancer that starts in either the colon or rectum. According to the International Agency for Research on Cancer, CRC is the third most prevalent cancer worldwide, associated with more than 935,000 deaths in 2020.5 In the U.S., it is estimated that 153,000 patients will be diagnosed with CRC and 53,000 deaths from the disease will occur in 2023.6 In Europe, CRC was the second most common cancer in 2020 with approximately 520,000 new cases and 245,000 deaths. In Japan, CRC was the most common cancer with an estimated 148,000 new cases and 60,000 deaths in 2020.5 Although early-stage CRC can be surgically resected, metastatic CRC remains an area of high unmet need with poor outcomes and limited treatment options. Some patients with metastatic CRC may benefit from personalized therapeutic strategies based on molecular characteristics; however, most patients have tumors that do not harbor actionable mutations.7,8,9,10,11

## 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 disease, plasma-derived therapies, neuroscience, oncology 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.](https://www.takeda.com/)

## About HUTCHMED

HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and 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 it has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three oncology drugs now approved and marketed in China. For more information, please visit: [www.hutch-med.com](https://www.hutch-med.com/) or follow us on [LinkedIn.](https://www.linkedin.com/company/hutchmed/)

## Takeda Media Contacts:

### Japanese Media

Jun Saito

<Jun.Saito@takeda.com>

### U.S. and International Media

Sara Noonan

[Sara.Noonan@takeda.com ](mailto:Sara.Noonan@takeda.com)+1 (508) 566-2408

Emma Nash

<Emma.Nash@takeda.com> +1 (404) 927-9113

## HUTCHMED Contacts:

### Investor Enquiries

Mark Lee, Senior Vice President	+852 2121 8200

Annie Cheng, Vice President	+1 (973) 306-4490

### Media Enquiries

**Americas –** Brad Miles, Solebury Strategic Communications	+1 (917) 570 7340 (Mobile) / <bmiles@soleburystrat.com>

**Europe –** Ben Atwell / Alex Shaw, FTI Consulting	+44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) <HUTCHMED@fticonsulting.com>

**Asia –** Zhou Yi, Brunswick 	+852 9783 6894 (Mobile) <HUTCHMED@brunswickgroup.com>

### Nominated Advisor

Atholl Tweedie / Freddy Crossley / Daphne Zhang, Panmure Gordon	+44 (20) 7886 2500

## Takeda 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.

## Takeda 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/> or at [www.sec.gov](http://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.

## HUTCHMED 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 submission of a NDA for fruquintinib for the treatment of CRC with the FDA and the timing of such submission, the therapeutic potential of fruquintinib for the treatment of patients with CRC and the further clinical development of fruquintinib 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 NDA approval of fruquintinib for the treatment of patients with CRC or other indications in the U.S. or other jurisdictions such as Europe or Japan, its potential to gain approvals from regulatory authorities on an expedited basis or at all; the efficacy and safety profile of fruquintinib; HUTCHMED’s ability to fund, implement and complete its further clinical development and commercialization plans for fruquintinib; the timing of these events; each party’s ability to satisfy the terms and conditions under the license agreement; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials or the regulatory pathway for fruquintinib; Takeda’s ability to successfully develop and commercialize fruquintinib; and the impact of the COVID-19 pandemic on general economic, regulatory and political conditions. In addition, as certain studies rely on the use of other drug products such as paclitaxel as combination therapeutics with fruquintinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of these therapeutics. Such forward-looking statements include, without limitation, statements regarding the plan to develop and commercialize fruquintinib under the license agreement; potential payments under the license agreement, including the upfront payment and any milestone or royalty payments; potential benefits of the license agreement; and HUTCHMED’s strategy, goals and anticipated milestones, business plans and focus. 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, on AIM and on The Stock Exchange of Hong Kong Limited. 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.

## Takeda 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.

1. Xu X, et al. Efficacy and safety of regorafenib and fruquintinib as third-line treatment for colorectal cancer: a narrative review. Transl Cancer Res 2022;11(1):276-287. doi: 10.21037/tcr-20-3539.

2. Sun Q, et al. Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy, *Cancer Biol Ther*. 2014;15:12, 1635-1645. doi: 10.4161/15384047.2014.964087.

3. Li J, et al. Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial. JAMA. 2018;319(24):2486-2496. doi:10.1001/jama.2018.7855.

4. Dasari NA, et al. LBA25 – FRESCO-2: A global phase 3 multiregional clinical trial (MRCT) evaluating the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer. Ann Oncol. 2022 Sep;33(suppl_7): S808-S869. doi: 10.1016/annonc/annonc1089.

5. Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660.

6. Siegel RL, et al. Colorectal cancer statistics, 2023 [published online ahead of print, 2023 Mar 1]. CA Cancer J Clin. 2023; 73(3):233-254. doi:10.3322/caac.21772.

7. Bando H, et al. Therapeutic landscape and future direction of metastatic colorectal cancer. Nat Rev Gastroenterol Hepatol 2023;20(5)306-322. doi:10.1038/s41575-022-00736-1.

8. D'Haene N, et al. Clinical application of targeted next-generation sequencing for colorectal cancer patients: a multicentric Belgian experience. Oncotarget. 2018;9(29):20761-20768. Published 2018 Apr 17. doi:10.18632/oncotarget.25099.

9. Venderbosch, et al. Mismatch repair status and braf mutation status in metastatic colorectal cancer patients: A pooled analysis of the Cairo, Cairo2, coin, and Focus Studies. *Clinical Cancer Res*. 2014;20(20):5322–5330. doi:10.1158/1078-0432.ccr-14-0332.

10. Koopman, M., et al. Deficient mismatch repair system in patients with sporadic advanced colorectal cancer. *Br J Cancer.* 209;100(2), 266–273. doi:10.1038/sj.bjc.6604867.

11. Ahcene Djaballah S, et al. HER2 in Colorectal Cancer: The Long and Winding Road From Negative Predictive Factor to Positive Actionable Target.Am Soc Clin Oncol Educ Book. 2022;42:1-14. doi:10.1200/EDBK_351354.

Takeda and HUTCHMED Announce Marketing Authorization Application of Fruquintinib for Previously Treated Metastatic Colorectal Cancer Validated by the European Medicines Agency

## News Releases



Divider Section

**Author: Teresa Bitetti, President, Global Oncology Business Unit**

I recently had a conversation with a good friend of mine who is a colorectal cancer (CRC) survivor. It was a particularly poignant get together as this was the first time we had chatted at length since Takeda acquired the license for a promising treatment in CRC. As my friend shared with me her personal experience with cancer, we also discussed the challenges faced by many beyond their initial diagnosis.

From financial and job insecurity, to depression and anxiety, to caregiving responsibilities – cancer treatment can be all-consuming. And while developing innovative medicines to treat cancer is at the heart of what we do as a pharmaceutical company, there is a lesser-known part as critical as the medicine – treating the whole patient. It’s this care beyond medicine where we have devoted more support in recent years.

## Mental Health and Well-Being

A cancer diagnosis can take an incredible toll on mental and emotional health, and recognizing changes in mood and behavior are critical during the journey according to the [American Cancer Society](https://www.cancer.org/cancer/managing-cancer/side-effects/emotional-mood-changes.html). Approximately 35% of patients diagnosed with cancer are impacted by a psychiatric disorder, and another 20% experience clinically relevant distressing psychosocial conditions such as demoralization and health anxiety.1 Research has shown that cancer patients receiving mental health support have better outcomes.2 Unfortunately, while mental health support may be a key part of a patient’s treatment journey, it is not always incorporated.3

Fortunately, there are several ways patients can be supported as they navigate the physical and emotional aspects of cancer. I am impressed by the resources that many of our partner patient advocacy organizations such as [CancerCare](https://www.cancercare.org/) provide – including emotional, practical and financial support – to navigate resources and the underlying emotions associated with diagnosis and treatment.

## Life Necessities and Obligations

A cancer diagnosis does not put life on pause. Patients may still need to feed themselves (and also family members), keep a roof over their heads, continue working, among many other aspects of life. Cancer is stressful enough without the added component of determining how to afford life.

Financial hardship impacts one in three patients diagnosed with cancer. And the risks disproportionality affect those who are socioeconomically disadvantaged and working-aged patients.4 The anxiety and stress of affording basic necessities can lead to poorer mental health, which can lead to poorer outcomes, perpetuating a vicious cycle. Fortunately, organizations such as [Family Reach ](https://familyreach.org/)provide resources to help patients navigate non-medical expenses. No one should have to make the decision to put treatment on hold to keep food on their table or the lights on at home.

In addition, patients may also be caregivers – to children, to aging parents, to pets – a role that does not disappear at cancer diagnosis. Caregiving can be emotionally and physically taxing even without managing a cancer diagnosis and treatment. Organizations such as [Cancer Support Community](https://www.cancersupportcommunity.org/) offer resources to support dialogue between patient and those in their care as they navigate this journey together.

Cancer treatment is more than medicine. It’s the collaboration and commitment of many stakeholders to ensure that patients receive the care necessary to navigate their journey. At Takeda, I’m proud we partner with patient organizations around the globe – to raise awareness and provide support to help ensure the whole patient is being treated. This is the way we will truly reach our aspiration to cure cancer.

## References:

1. Caruso R, Breitbart W. Mental health care in oncology. Contemporary perspective on the psychosocial burden of cancer and evidence-based interventions. *Epidemiol Psychiatr Sci.* 2020;29:e86. doi:10.1017/S2045796019000866

2. Berchuck JE, Meyer CS, Zhang N, et al. Association of Mental Health Treatment With Outcomes for US Veterans Diagnosed With Non-Small Cell Lung Cancer. *JAMA Oncol.* 2020;6(7):1055-1062. doi:10.1001/jamaoncol.2020.1466

3. Oncology TL. Provision of mental health care for patients with cancer. *The Lancet Oncology*. 2021;22(9):1199. doi:10.1016/S1470-2045(21)00480-0

4. Smith GL, Lopez-Olivo MA, Advani PG, et al. Financial Burdens of Cancer Treatment: A Systematic Review of Risk Factors and Outcomes. *J Natl Compr Canc Netw.* 2019;17(10):1184-1192. doi:10.6004/jnccn.2019.7305

Hear from Teresa Bitetti, President of the Global Oncology Business Unit, as she discusses how Takeda and its partners are providing cancer care beyond medicine by supporting other areas of patients' lives, such as finances and mental health.

Cancer Treatment is More Than Medicine

Innovations in data, digital and technology continue to drive the latest advancements in oncology research, propelling us into the future of therapeutic development and identifying ways to more efficiently deliver new medicines to patients. As we learn to apply the tools provided by this field, we are offered the chance to discover and establish improved standards of care for people living with cancer. How can we use the latest technology to enhance our medicines and make a real difference in the lives of patients?

Listen to Takeda’s Christine Ward, Ph.D., Head of Oncology and Cell Therapy Precision & Translational Medicine, and Julie Dixon, Ph.D., Head of Global Regulatory Affairs, as they answer this question and reflect on how data, digital and technology is transforming their work and redefining possibilities for the next era of oncology.


Listen to Takeda’s Christine Ward, Ph.D., Head of Oncology and Cell Therapy Precision & Translational Medicine, and Julie Dixon, Ph.D., Head of Global Regulatory Affairs, as they answer this question and reflect on how data, digital and technology is transforming their work and redefining possibilities for the next era of oncology.

Embracing Innovation: How Today’s Tech is Transforming Translational Medicine for Patients with Cancer

Over the last decade, the multiple myeloma treatment landscape has rapidly evolved. While scientific innovation and the emergence of new therapies have helped provide a renewed sense of hope to people living with multiple myeloma, it has also made navigating the treatment journey more complex.

Given this, it is more critical than ever to ensure that we are stepping up to provide optimal education and support for patients, so they have access to the right resources and information based on their needs, concerns, desires and treatment goals. The way we can do this is by going directly to the source and hearing from patients.

At Takeda, we are focused on continuing to expand the programs that allow us to gather deep, unfiltered insights directly from patients and their care partners to better understand the needs of the myeloma community. In celebration of Myeloma Action Month, I wanted to shed light on one of Takeda Oncology’s trailblazing programs and how it has given us invaluable insights into the myeloma patient experience.

## The Patient Advocacy Liaisons

The Patient Advocacy Liaisons, or PALs, are a field-based team of myeloma experts whose mission is to deliver meaningful disease education to patients and their care partners with a focus on patient empowerment.

The program was established in 2021, and since then, the PALs have delivered more than 250 educational presentations to nearly 5,000 patients and care partners based directly on what we hear from patients – namely, the gaps in knowledge they have about their disease. These presentations take place in the support group setting or during patient organization events. These ~5,000 people have shared the information they learn within their own networks, creating a much larger reach. In the words of one of our patient leadership council members, “when you educate one patient, you educate thousands.”

PALs don’t just talk to people with myeloma, they talk *with* them, gathering information about their unmet needs. Following a presentation, PALs actively request feedback from attendees, and take those unfiltered insights and learnings into consideration when developing new educational content so it reflects the most timely and relevant educational needs facing patients today. PALs also co-create content with key opinion leaders including members of our Patient Leadership Council and expert patient advocates, ensuring it is easy to understand and optimized for the patient and care partner audience.

Our current PALs are Tara Roy MS, NP, AOCNP, and Rebekah Tobin, RN, BSN. Over the last year, they have delivered presentations aimed at helping patients understand their risk status, side effect management, lab values, cancer survivorship and wellness, infection risk, the importance of vaccinations and more. Our hope is that when patients are armed with this information, they can become stronger self-advocates and have a more-informed, ongoing dialogue with their care team, which can ultimately improve patient outcomes.

PAL Rebekah Tobin shared, “hearing the success stories post-program from people and care partners utilizing our PALs resources to help overcome their barriers is extremely rewarding. People living with myeloma and their care partners see that we take the feedback they provide and create presentations and resources which make them feel seen, heard, understood and valued. This aspect is incredibly important in distinguishing the PAL role from other advocacy roles in the industry.”

Our amazing partner organizations, like HealthTree and the International Myeloma Foundation, allow us to utilize their existing, well-established structures that provide patients and care partners with education and support to serve as forums for our programs. Patients can look out for upcoming events that the PALs will attend to deliver presentations through patient organization websites and social media channels.

Looking ahead, based on the feedback we have received, we plan to deliver presentations on strengthening communication with healthcare teams and focusing on mental health and resilience when navigating a myeloma diagnosis. We also ultimately hope to expand the PALs program into other disease areas.

“One of the most rewarding aspects as a PAL is knowing the positive impact made on patients and their caregivers as they gain the knowledge they need through our disease-based educational programs, take the information learned back to their healthcare team and feel empowered to take control of their care as they navigate through their cancer journey,” said PAL Tara Roy.


Over the last decade, the multiple myeloma treatment landscape has rapidly evolved. While scientific innovation and the emergence of new therapies have helped provide a renewed sense of hope to people living with multiple myeloma, it has also made navigating the treatment journey more complex.

Empowering Patients by Elevating Their Voices: The Patient Advocacy Liaisons Program

The decisions that a health care provider (HCP) makes immediately after a patient’s cancer diagnosis often define their treatment journey. For patients with lung cancer, one of those critical decisions is when and how to approach diagnostic testing to ensure any cancer-driving mutation(s) are properly identified. Having this information confirmed from the start allows HCPs to prescribe treatment(s) that specifically target their patient’s disease, giving them the best possible chance to optimize outcomes.1
Next-generation sequencing, or NGS, provides comprehensive testing – helping to optimize diagnosis and ensure HCPs consider all potential treatment options for their patients, including any targeted options that may be available. In rare lung cancers – like epidermal growth factor receptor (EGFR) Exon20 insertion mutation-positive (insertion+) non-small cell lung cancer (NSCLC) – NGS testing is a useful tool due to the distinct nature of the mutations.2
So why is this critical tool – one that has improved our understanding of cancer development and progression – not being utilized universally as standard of care?3
We gathered perspectives from several experts on what is preventing the universal adoption of NGS, and how these barriers need to be broken down to help HCPs make their care approach stronger and, ultimately, improve outcomes for patients.

## Lack of Awareness

It’s important to acknowledge that not all forms of testing are created equal. Due to the heterogeneity in length and positions of certain mutations, NGS is a more comprehensive option for detecting compared to polymerase chain reaction, or PCR, testing, which doesn’t have the same capabilities.2,4 For example, PCR testing is projected to capture about 50% of EGFR Exon20 insertion+ cases.5 Due to its limited ability to identify certain mutations, PCR tests may prevent patients from being prescribed appropriate treatments designed for their specific cancer, potentially preventing them from achieving their desired health outcomes.2,6
Wider adoption of NGS testing has enabled the identification of rare mutations that may be missed with commercially available tests, leading to a growing number of previously unidentified mutations. This has, in turn, facilitated the use of [precision medicine](https://www.fda.gov/medical-devices/in-vitro-diagnostics/precision-medicine).7-8 Despite these benefits and capabilities to pinpoint a patient’s lung cancer, NGS testing continues to be underutilized in the clinical setting.9 According to a *JCO Precision Oncology* [study](https://ascopubs.org/doi/full/10.1200/PO.22.00246) that evaluated patients with newly diagnosed advanced NSCLC, approximately 64% of potentially eligible patients for precision oncology therapies appropriate for their lung cancer did not benefit from them due to factors associated with clinical gaps, including pre-analytic biomarker testing.9 Too few clinicians are aware of the potential impact of NGS testing, and broader awareness is needed to ensure lung cancer patients are able to benefit from it.9

## Logistical Concerns

One of the common concerns from those who *are* aware of NGS tests is that results take longer than PCR tests, thus pushing back the timeline for when patients can begin treatment.3
While time is of the essence when diagnosing a disease as serious as lung cancer, waiting for the results of the NGS test will ultimately benefit the patient.3,10 HCPs should look at this issue comprehensively and recognize that prescribing the wrong therapy can cause a negative ripple effect and impact several aspects of the patient’s journey.9 Prescribing the wrong treatment may result in the patient’s cancer progressing more quickly or acquiring resistance mutations that complicate treatment sequencing.9,11-12 When NGS testing is taken into consideration at the very beginning, HCPs can ensure that all potential diagnoses and treatment options are initially explored, facilitating a path for patients to receive an optimized diagnosis and timely treatment decisions.1,9

## Reimbursement

PCR tests are the more commonly used testing method because equipment to run them is more accessible and are generally perceived as more cost-effective.3,11 However, in recent years payers have grown increasingly receptive to reimbursing for NGS tests. There are several ways coverage can be achieved for NGS testing.13 Local coverage determination, in which a Medicare Administrative Contractor reviews a test performed in that jurisdiction.

* National coverage determination, which provides access to testing for all Medicare patients nationally.
* Through private payers, which each generate their own coverage policy. Coverage policies from payers can vary significantly and may address all NGS-based tests or just one specific diagnostic test.
* Through Medicaid, in which oncology and biomarker tests are paid for directly on a state-by-state basis through diagnostic companies or health insurance.
 The most influential factor on coverage and reimbursement decisions is the clinical evidence that supports the validity of the test. As the reimbursement outlook improves and more targeted therapies are approved, pathologists anticipate an increase in NGS-based testing moving forward.13

Using NGS testing provides patients with an optimized diagnosis and thus the opportunity to receive a treatment designed to target their disease at the molecular level.1 This is why Takeda partners with industry stakeholders and companies like Thermo Fisher Scientific and Foundation Medicine, in order to address the urgent need for broader access to genomic tests, ultimately expanding treatment options for patients. Takeda remains dedicated to supporting these efforts to expand the availability and accessibility of NGS testing so that more patients can benefit from and have access to life-transforming medicine.

*Takeda Oncology and Foundation Medicine are currently partnering on the development of Foundation Medicine’s tissue- and blood-based companion diagnostics, with the goal of improving outcomes for people with* [*anaplastic lymphoma kinase-positive (ALK+)*](https://www.foundationmedicine.com/press-releases/1f035abc-35f0-417f-bf06-2115eb386579) *and EGFR Exon20 insertion+ mNSCLC. To learn more about the* [*partnership*](https://www.foundationmedicine.com/press-releases/7c611e86-4d8a-452e-9f41-8fda9901af36) *or Foundation Medicine’s approach to genomic profiling, you can visit* [*https://www.foundationmedicine.com/*](https://www.foundationmedicine.com/)*.*

### References

1. Pennell N et al. *JCO Precision Oncology*. Economic Impact of Next-Generation Sequencing Versus Single-Gene Testing to Detect Genomic Alterations in Metastatic Non-Small-Cell Lung Cancer Using a Decision Analytic Model. 2019.
2. Viteri S, Minchom A, Bazhenova L, et al. \_Molecular Oncology.\_Frequency, underdiagnosis, and heterogeneity of epidermal growth factor receptor exon 20 insertion mutations using real-world genomic datasets. 2022;1:1-8
3. Berger et al. *Nat Rev Clin Oncol.* The emerging clinical relevance of genomics in cancer medicine. 2018; 15(6):353-365
4. Khoo C, et al. *Transl Lung Cancer Res*. Molecular methods for somatic mutation testing in lung adenocarcinoma: EGFR and beyond. 2015;4:126-141
5. Ou S, Hong J, Lin H, et al. *Journal of Thoracic Oncology.* Distribution and Detectability of EGFR Exon20 Insertion Variants in Non-Small Cell Lung Cancer. 2021;16:S928-S929
6. Lin HM et al. *Journal of Thoracic Oncology* EGFR Testing Patterns and Detection of EGFR Exon 20 Insertions in the United States. 2022;3.
7. Food and Drug Administration. Precision Medicine. 2018. <https://www.fda.gov/medical-devices/in-vitro-diagnostics/precision-medicine>
8. Russo A, et al. *Oncotarget*. Heterogeneous Responses to Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) in Patients with Uncommon EGFR Mutations: New Insights and Future Perspectives in this Complex Clinical Scenario. 2015;6:26814-26825.
9. Sadik H, Pritchard D, Keeling DM, et al. *JCO Precision Oncology*. Impact of Clinical Practice Gaps on the Implementation of Personalized Medicine in Advanced Non–Small-Cell Lung Cancer.
 2022;6.
10. Cainao C et al. *Biology (Basel*). Next Generation Sequencing Technology in Lung Cancer Diagnosis. 2021; 10(9)
11. Schluckebier L, Caetano R, Garay OU, et al. National Library of Medicine. *BMC Cancer*. Cost-effectiveness analysis comparing companion diagnostic tests for EGFR, ALK, and ROS1 versus next-generation sequencing (NGS) in advanced adenocarcinoma lung cancer patients. 2020.
12. Pacini L et al. *Pharmcogenomics and Personalized Medicine*. Tackling Drug Resistance in EGFR Exon 20 Insertion Mutant Lung Cancer. 2021;14:1-17.
13. Ferrara et al. Pieran Dx. 2020 NGS Testing Reimbursement Overview Strategies for Clinical NGS Deck. 2019.

The decisions that a health care provider (HCP) makes immediately after a patient's cancer diagnosis often define their treatment journey.

Breaking Down Barriers Preventing the Use of NGS

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