June 26, 2024 7:45 pm ET
The letter didn’t establish any points with the efficacy or security knowledge submitted within the software
BASKING RIDGE, N.J. & RAHWAY, N.J., June 26, 2024 – The U.S. Meals and Drug Administration (FDA) has issued aComplete Response Letter (CRL) for the Biologics License Software (BLA) searching for accelerated approval of DaiichiSankyo (TSE: 4568) and Merck’s (often known as MSD exterior of america and Canada) (NYSE: MRK) patritumabderuxtecan (HER3-DXd) for the therapy of grownup sufferers with domestically superior or metastatic EGFR-mutated non-smallcell lung most cancers (NSCLC) beforehand handled with two or extra systemic therapies.
The CRL outcomes from findings pertaining to an inspection of a third-party manufacturing facility. TheCRL didn’t establish any points with the efficacy or security knowledge submitted.
Patritumab deruxtecan is a particularly engineered potential first-in-class HER3 directed DXd antibody drug conjugate(ADC) found by Daiichi Sankyo and being collectively developed by Daiichi Sankyo and Merck.
“We are going to work intently with the FDA and the third-party producer to deal with the suggestions as shortly as attainable inorder to deliver the primary HER3 directed medication to sufferers with previously-treated EGFR-mutated non-small cell lungcancer,” mentioned Ken Takeshita, MD, World Head, R&D, Daiichi Sankyo. “We stay assured within the means todevelop this medication to its full potential.”
“Sufferers with beforehand handled EGFR-mutated non-small cell lung most cancers usually expertise recurrence and havelimited therapy choices,” mentioned Marjorie Inexperienced, MD, Senior Vice President and Headof Oncology, World Scientific Improvement, Merck Analysis Laboratories. “We’re dedicated to working with Daiichi Sankyo and the FDA to prioritize making patritumab deruxtecan accessible to those sufferers in want.”
The BLA relies on the first outcomes from the HERTHENA-Lung01 pivotal part 2 trial thatwere introduced atthe IASLC 2023 World Convention on Lung Most cancers (#WCLC23) and concurrently printed within the Journalof Scientific Oncology.
In HERTHENA-Lung01, patritumab deruxtecan was studied in 225 sufferers with EGFR-mutated domestically superior ormetastatic NSCLC following illness development with an EGFR TKI and platinum-based chemotherapy, which demonstratedan goal response charge (ORR) of 29.8% (95% CI: 23.9-36.2), together with one full response and 66 partialresponses. The median length of response (DoR) was 6.4 months (95% CI: 4.9-7.8).
The protection profile of patritumab deruxtecan noticed in HERTHENA-Lung01 was in keeping with earlier part 1 clinicaltrials in NSCLC with a therapy discontinuation charge of seven.1% resulting from treatment-emergent opposed occasions (TEAEs).Grade 3 or larger TEAEs occurred in 64.9% of sufferers. The commonest (≥5%) grade 3 or larger TEAEs werethrombocytopenia (21%), neutropenia (19%), anemia (14%), leukopenia (10%), fatigue (6%), hypokalemia (5%) andasthenia (5%). Twelve sufferers (5.3%) had confirmed treatment-related interstitial lung illness (ILD) as determinedby an unbiased adjudication committee. One grade 5 ILD occasion was noticed.
About HERTHENA-Lung01
HERTHENA-Lung01 is a worldwide, multicenter, open-label, two-arm part 2 trial evaluating the protection and efficacy ofpatritumab deruxtecan in sufferers with EGFR-mutated domestically superior or metastatic NSCLC following diseaseprogression with an EGFR TKI and platinum-based chemotherapy. Sufferers had been randomized 1:1 to obtain 5.6 mg/kg(n=225) or an uptitration routine (n=50). The uptitration arm was discontinued because the dose of 5.6 mg/kg ofpatritumab deruxtecan was chosen following a risk-benefit evaluation carried out from the part 1 trial assessing the doses in the same patientpopulation.
The first endpoint of HERTHENA-Lung01 was ORR as assessed by blinded unbiased central evaluation (BICR). Secondaryendpoints included DoR, progression-free survival, illness management charge, and time to response– all assessed by each BICR and investigator evaluation – in addition to investigator-assessed ORR, total survival,security and tolerability.
HERTHENA-Lung01 enrolled sufferers in Asia, Europe, North America and Oceania. For extra details about the trial,go to ClinicalTrials.gov.
About EGFR-mutated non-small cell lung most cancers
Roughly 226,000 lung most cancers instances had been identified within the U.S. in 2022. Lung most cancers is the third most commoncancer and the main explanation for cancer-related deaths within the U.S. NSCLC accounts for roughly 81% of all lungcancers within the U.S., with 52% having distant unfold at analysis. EGFR mutations happen in roughly 1 in 5patients with NSCLC in Western populations.
About HER3
HER3 is a member of the EGFR household of receptor tyrosine kinases. It’s estimated that about 83% of main NSCLCtumors and 90% of superior EGFR-mutated tumors specific HER3 after prior EGFR TKI therapy. HER3 is related withpoor therapy outcomes, together with shorter relapse-free survival and considerably decreased survival. There iscurrently no HER3 directed remedy accepted for the therapy of any most cancers.
About patritumab deruxtecan
Patritumab deruxtecan (HER3-DXd) is an investigational HER3 directed ADC. Designed utilizing Daiichi Sankyo’s proprietaryDXd ADC Expertise, patritumab deruxtecan consists of a totally human anti-HER3 IgG1 monoclonal antibody attachedto a lot of topoisomerase I inhibitor payloads (an exatecan spinoff, DXd) by way of tetrapeptide-based cleavablelinkers.
Patritumab deruxtecan was granted Breakthrough TherapyDesignation by the U.S. Meals and Drug Administration in December 2021 for the therapy of sufferers withEGFR-mutated domestically superior or metastatic NSCLC with illness development on or after therapy with athird-generation TKI and platinum-based therapies.
Patritumab deruxtecan is at the moment being evaluated as each a monotherapy and together with different therapies in aglobal improvement program, which incorporates HERTHENA-Lung02, a part 3 trial evaluating theefficacy and security of patritumab deruxtecan versus platinum-based chemotherapy in sufferers with EGFR-mutatedlocally superior or metastatic NSCLC following illness development on or after therapy with a third-generationEGFR TKI; HERTHENA-Lung01, a part 2 trial inmetastatic or domestically superior NSCLC with an activating EGFR mutation beforehand handled with not less than one EGFR TKIand one platinum-based chemotherapy-containing routine; HERTHENA-PanTumor01, a part 2 trial in domestically superior ormetastatic stable tumors, together with melanoma, gastric and head and neck most cancers, amongst different varieties of most cancers,beforehand handled with not less than one prior systemic remedy; a part 1 trial together with osimertinib inEGFR-mutated domestically superior or metastatic NSCLC; and a part 1 trial in beforehand handled sufferers withadvanced NSCLC. A part 1/2 trial in HER3 expressingmetastatic breast most cancers additionally has been accomplished.
Concerning the Daiichi Sankyo and Merck collaboration
Daiichi Sankyo and Merck entered into a worldwide collaboration in October2023 to collectively develop and commercialize patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd)and raludotatug deruxtecan (R-DXd), besides in Japan the place Daiichi Sankyo will preserve unique rights. DaiichiSankyo might be solely chargeable for manufacturing and provide.
Concerning the DXd ADC portfolio of Daiichi Sankyo
The DXd ADC portfolio of Daiichi Sankyo at the moment consists of six ADCs in medical improvement throughout a number of typesof most cancers. ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, are beingjointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directedADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC,are being collectively developed and commercialized globally with Merck. DS-3939, a TA-MUC1 directed ADC, is beingdeveloped by Daiichi Sankyo.
Designed utilizing Daiichi Sankyo’s proprietary DXd ADC Expertise to focus on and ship a cytotoxic payload insidecancer cells that specific a particular cell floor antigen, every ADC consists of a monoclonal antibody hooked up to anumber of topoisomerase I inhibitor payloads (an exatecan spinoff, DXd) by way of tetrapeptide-based cleavable linkers.
Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan and DS-3939 areinvestigational medicines that haven’t been accepted for any indication in any nation. Security and efficacy havenot been established.
About Daiichi Sankyo
Daiichi Sankyo is an revolutionary international healthcare firm contributing to the sustainable improvement of society thatdiscovers, develops and delivers new requirements of care to counterpoint the standard of life around the globe. With morethan 120 years of expertise, Daiichi Sankyo leverages its world-class science and expertise to create newmodalities and revolutionary medicines for individuals with most cancers, cardiovascular and different ailments with excessive unmetmedical wants. For extra info, please go to www.daiichisankyo.com.
Merck’s give attention to most cancers
On daily basis, we observe the science as we work to find improvements that may assist sufferers, it doesn’t matter what stage ofcancer they’ve. As a number one oncology firm, we’re pursuing analysis the place scientific alternative and medicalneed converge, underpinned by our numerous pipeline of greater than 25 novel mechanisms. With one of many largestclinical improvement applications throughout greater than 30 tumor sorts, we try to advance breakthrough science that willshape the way forward for oncology. By addressing obstacles to medical trial participation, screening and therapy, wework with urgency to cut back disparities and assist guarantee sufferers have entry to high-quality most cancers care. Ourunwavering dedication is what’s going to deliver us nearer to our objective of bringing life to extra sufferers with most cancers. Formore info, go to https://www.merck.com/analysis/oncology/.
About Merck
At Merck, often known as MSD exterior of america and Canada, we’re unified round our function: We use the powerof modern science to save lots of and enhance lives around the globe. For greater than 130 years, now we have introduced hope tohumanity by means of the event of necessary medicines and vaccines. We aspire to be the premier research-intensivebiopharmaceutical firm on this planet – and right now, we’re on the forefront of analysis to ship revolutionary healthsolutions that advance the prevention and therapy of ailments in individuals and animals. We foster a various andinclusive international workforce and function responsibly on daily basis to allow a secure, sustainable and wholesome future forall individuals and communities. For extra info, go to www.merck.com and connectwith us on X (previously Twitter), Fb, Instagram, YouTube and LinkedIn.
Ahead-Trying Assertion of Merck & Co., Inc., Rahway, N.J., USA
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