tecemotide tecemotide tecemotide (inn; emepepimut-s (usan); formerly known as blp25 or emd 531444) is a synthetic lipopeptide that is used as antigen in an investigational therapeutic cancer vaccine (formerly known as stimuvax, l-blp25, blp25 liposomal vaccine, or blp25 liposome vaccine). the investigational therapeutic cancer vaccine is designed to induce a cellular immune response to cancer cells that express muc1, a glycoprotein antigen that is widely over-expressed on common cancers such as lung cancer, breast cancer, prostate cancer, and colorectal cancer. the cellular immune response may lead to a rejection of tumor tissue expressing the muc1 antigen. tecemotidevaccine descriptiontargetmuc1vaccine typeprotein subunitclinical dataother namesemepepimut-s; stimuvax; blp25; emd 531444; l-blp25; blp25 liposomal vaccineidentifierscas number221214-84-2 (antigen)uniiq7y026g2cxchemical and physical dataformulac124h203n33o38 collaboration tecemotide was developed – until clinical trial phase ii – by the canadian biotech company biomira inc., which changed its company name to oncothyreon inc. in 2007. oncothyreon is now located in seattle, washington, and it changed its name to sgen after a merger and acquisition in march 2018. in 2001, merck kgaa, of darmstadt, germany, entered into a collaboration and supply agreement with biomira. in 2007, merck kgaa acquired the exclusive worldwide marketing rights from biomira, and merck kgaa has since then been entirely responsible for the further clinical development of tecemotide. in 2008, merck kgaa acquired the manufacturing rights for tecemotide from oncothyreon. in 2011, ono pharmaceutical company, of japan, acquired a co-development and co-marketing license for tecemotide in japan; ono paid merck kgaa 5 million euros. composition tecemotide is a synthetic lipopeptide that is 27 amino acids long. its molecular formula is c124h203n33o38, and its amino acid sequence is s t a ppah g vtsapdtrpapgstappkg. the first 25 amino acids of tecemotide are derived from the mucin 1 (muc1, carcinoma-associated mucin, episialin, or cd227) sequence. the 26th modified amino acid, k, is palmityl-lysine (n6-(1-oxohexadecyl)-l-lysine), and the 27th is glycine. structure of the cancer vaccine structure of the cancer vaccine. the antigen tecemotide (orange) and the adjuvant mpl (dark blue) are anchored in the membrane of the liposome. the liposome is formed by the lipids (light blue). in the investigational therapeutic cancer vaccine (formerly known as stimuvax, l-blp25, blp25 liposomal vaccine or blp25 liposome vaccine), the antigen tecemotide is anchored — together with the adjuvant 3-o-deacyl-4′-monophosphoryl lipid a (mpl) — in the membrane of the liposome made from the lipids cholesterol, dimyristoyl phosphatidylglycerol (dmpg), and dipalmitoyl phosphatidylcholine. mpl is a derivative of the lipid a molecule found in the membrane of gram-negative bacteria used as an adjuvant to initiate a non-specific immune stimulus, thereby stimulating the activation of antigen-presenting cells (apcs) through the toll-like receptor 4 (tlr-4) as well as macrophages. mpl is also used as an adjuvant in other vaccines, like cervarix, a vaccine against certain types of cancer-causing human papillomavirus (hpv). the precise mixture of lipids in the vaccine, as well as providing the structure of the liposome, is also formulated to enhance the uptake of the vaccine by the aforementioned antigen-presenting cells. the cancer vaccine is a lyophilized powder, which is formulated to contain 300 μg of tecemotide and 150 μg of mpl per vial. clinical trials overview and results of all trials tecemotide clinical trials (as of september 2, 2014) sorted by (estimated) primary completion date: clinical trials: lung cancer, breast cancer, prostate cancer, colorectal cancer, and multiple myeloma nct number /titleother idsstart date(estimated) primary completion daterecruitmentconditionsinterventionsphasesenrollment (patients)sponsor / collaborators clinical trial number nct00157209 for "phase iib randomized controlled study of blp25 liposome vaccine for immunotherapy of non-small cell lung cancer" at clinicaltrials.govb25-lg-304 / emr 63325-005august 2000march 2006completedlung neoplasms, carcinoma, non-small-cell lungbiological: blp25 liposome vaccine plus best supportive care; other: best supportive care (bsc)phase 2171merck kgaa results: a phase iib clinical trial of 171 patients with inoperable stage iiib non-small-cell lung cancer (nsclc), in which tecemotide showed a trend towards extending median overall survival from 13.3 months for patients receiving best supportive care (bsc) to 30.6 months for patients receiving tecemotide plus bsc. although this represents a subgroup analysis that is not statistically significant (with a nonsignificant p-value: p = 0.16), the magnitude of the difference and its durability over a prolonged period of follow up suggest an efficacy signal for the vaccine and would support further testing of tecemotide in a definitive phase iii trial. reported side effects included mild-to-moderate flu-like symptoms, gastrointestinal disturbances, and mild injection-site reactions.butts c, maksymiuk a, goss g, soulières d, marshall e, cormier y, et al. (september 2011). "updated survival analysis in patients with stage iiib or iv non-small-cell lung cancer receiving blp25 liposome vaccine (l-blp25): phase iib randomized, multicenter, open-label trial". journal of cancer research and clinical oncology. 137 (9): 1337–1342. doi:10.1007/s00432-011-1003-3. pmid 21744082. s2cid 25108866. nct00157196 safety study of blp25 liposome vaccine in non-small cell lung cancer patients with unresectable stage iii diseaseb25-lg-305 / emr 63325-006april 2005september 2009completedcarcinoma, non-small-cell lung, lung neoplasmsbiological: blp25 liposome vaccinephase 222merck kgaa nct00925548 stride - stimulating immune response in advanced breast cancerstride, emr 200038–010, 2008-005544-17september 2009august 2010terminatedbreast cancerbiological: tecemotide (l-blp25) and hormonal treatment, biological: placebo of tecemotide (l-blp25) and hormonal treatment, drug: cyclophosphamide, drug: sodium chloride (nacl)phase 316emd serono a thirty-site phase iii trial (stride) began in september 2009 on 900 women. the purpose of this study is to determine whether the addition of tecemotide to hormonal treatment is effective in prolonging progression-free survival in postmenopausal women with endocrine-sensitive inoperable locally advanced, recurrent, or metastatic breast cancer. results: the u.s. food and drug administration (fda) put the phase iii stride trial on hold in march 2010 after a patient participating in a phase ii clinical trial with tecemotide in patients with multiple myeloma developed encephalitis. the study was terminated in august 2010 (16 patients were enrolled in the study). nct01094548 study of stimuvax in patients with slowly progressive multiple myeloma with no symptoms and who have had no chemotherapyemr63325-008february 2008february 2011completedmultiple myelomabiological: l-blp25, cyclophosphamide prior to first vaccination, biological: l-blp25phase 234merck kgaa nct00409188 cancer vaccine study for unresectable stage iii non-small cell lung cancerstart, emr 63325-001january 2007august 2012completednon-small cell lung cancerbiological: tecemotide (l-blp25), biological: placebophase 31513emd serono, merck kgaa results: the primary endpoint of overall survival was not met in the start trial. however, the exploratory subgroup analysis in the start trial generated a reasonable hypothesis to warrant additional study.kolahdooz f, jang sl, corriveau a, gotay c, johnston n, sharma s (october 2014). "knowledge, attitudes, and behaviours towards cancer screening in indigenous populations: a systematic review". the lancet. oncology. 15 (11): e504–e516. doi:10.1016/s1470-2045(14)70508-x. pmid 25281469. nct01731587 anti-cancder muc1-specific immunotherapy for unresectable stage iii non-small cell lung cancerfingerprint, emr 63325–019, 2012-001435-31withdrawnnon-small cell lung cancer (nsclc) stage iiiother: biological: muc1 peptide specific immunotherapy, drug: cyclophosphamide (cpa)phase 10merck kgaa nct00960115 study of emd531444 in subjects with stage iii unresectable non-small cell lung cancer (nsclc) following primary chemoradiotherapyemr063325-009december 2008may 2014completednon-small cell lung cancerbiological: cyclophosphamide + emd531444 + bsc, biological: saline + placebo + bscphase 1, phase 2205merck kgaa, merck serono co., ltd., japan results: the analysis of emr 63325–009, a randomized, double-blind, placebo-controlled, phase i/ii study in japanese patients with stage iii unresectable, locally advanced nsclc who had received concurrent or sequential chemoradiotherapy (crt), with a minimum of two cycles of platinum-based chemotherapy and radiation dose ≥50 gy shows the following results: of the patients included in the phase ii part of the study, the majority had received concurrent crt. the results indicate that no effect has been observed for either the primary endpoint, overall survival (os), or any of the secondary endpoints (progression-free survival , time to progression , and time to treatment failure). an analysis of the reported adverse events has not identified a clinically meaningful difference in the frequency between treatment groups. merck serono made the recommendation to stop the investigational treatment for patients in the emr 63325-009 study in japan. eudract: 2011-004822-85 a prospective, open, randomized, phase-ii study of a therapeutic cancer vaccine (l-blp25, stimuvax) in the pre-operative treatment of women with primary breast cancerabcsg-34 / emr 63325-603jan 2012may 2014active, not recruitingbreast cancerl-blp25 (stimuvax), cyclophosphamide (cpa), letrozole, epirubicin, docetaxelphase 2400abcsg (austrian breast & colorectal cancer study group) results: 8 may 2012 enrollment expected to be completed in may 2014 first results available end of 2014 26 sept 2014 enrollment of 400 patients completed nct01507103 tecemotide (l-blp25) in rectal cancersprint, emr063325-013, 2011-000847-25february 2012june 2014active, not recruitingrectal cancercyclophosphamide (cpa), tecemotide (l-blp25)phase 2124merck kgaa nct00828009 blp25 liposome vaccine and bevacizumab after chemotherapy and radiation therapy in treating patients with newly diagnosed stage iiia or stage iiib non-small cell lung cancer that cannot be removed by surgerycdr0000632611, e6508december 2010january 2016recruitinglung cancerbiological: bevacizumab, biological: emepepimut-s, drug: carboplatin, drug: cyclophosphamide, drug: paclitaxel, radiation: radiation therapyphase 255eastern cooperative oncology group, national cancer institute (nci) nct01462513 l-blp25 in patients with colorectal carcinoma after curative resection of hepatic metastaseslicc01august 2011september 2016recruitingcolon carcinoma, rectum carcinomabiological: l-blp25, biological: placebophase 2159johannes gutenberg university mainz, dr. carl schimanski nct01496131 tecemotide (l-blp25) in prostate canceremr 63325–015, bb-ind 7787october 2011august 2017recruitingprostate cancerradiation: radiation therapy, drug: goserelin, drug: cyclophosphamide, drug: tecemotide (l-blp25)phase 248emd serono, national cancer institute (nci) nct02049151 tecemotide following concurrent chemo-radiotherapy for non-small cell lung cancerstart2, emr 63325–021, 2013-003760-30march 2014july 2018recruitingcarcinoma, non-small-cell lungdrug: tecemotide, drug: placebo, drug: cyclophosphamide (cpa), drug: saline (sodium chloride)phase 31002emd serono nct01423760 collect long-term data on subjects following participation in previous emd 531444 (l-blp25 or blp25 liposome vaccine) clinical trialsemr 63325-011january 2012december 2019enrolling by invitationnon-small cell lung cancer, multiple myelomabiological: tecemotide, other: no intervention262merck kgaa nct01015443 cancer vaccine study for stage iii, unresectable, non-small cell lung cancer (nsclc) in the asian populationinspire, emr63325-012december 2009may 2020recruitingnon-small cell lung cancerbiological: tecemotide (l-blp25), biological: placebophase 3500merck kgaa note: merck kgaa and oncothyreon are not reporting in their annual reports on colorectal cancer trials and prostate cancer trials overview of completed trials overview of completed tecemotide trials (as of september 2, 2014) where results have been published, sorted by primary completion date: idphaseindicationstartprimary completion datesummary of the results emr 63325-0052nsclcaugust 2000march 2006subgroup analysis favorable. start, emr 63325-0013nsclcjanuary 2007august 2012primary endpoint not met. subgroup analysis favorable. emr 63325-009 (japan study)1, 2nsclcdecember 2008may 2014primary endpoint and secondary endpoints not met. subgroup analysis not favorable. discontinued development on august 18 and september 12, 2014, oncothyreon and merck kgaa, respectively, reported that a randomized phase 1/2 study, emr 63325–009, of tecemotide compared to a placebo in japanese patients with stage iii non-small cell lung cancer did not meet its primary endpoint of an improvement in overall survival, and no treatment effect was seen in any of the secondary endpoints (progression-free survival, time to progression, or time to failure). merck made the recommendation to stop the investigational treatment of patients in the emr 63325-009 study in japan. furthermore, merck kgaa announced its decision to discontinue the phase iii start2 and inspire studies, and all other merck-sponsored clinical trials with tecemotide in nsclc, worldwide. merck will continue to supply tecemotide for ongoing investigator-sponsored trials in other indications in accordance with their agreements with the sponsors of these studies. drug development risks risks that could affect the further development of tecemotide published in the annual reports of oncothyreon (grantor of the license) and merck kgaa (license holder; responsible for clinical development, marketing and manufacturing) are listed in the following sections. efficacy as published so far, primary end points have not been met in the clinical studies, and tecemotide has shown treatment effects only in statistical analyses of certain subgroups. patent situation oncothyreon's patent protection for tecemotide in the u.s. was scheduled to expire in 2018. human resources in 2013, merck kgaa reported problems with recruiting and retaining qualified employees: "sourcing, recruiting and retaining specialists and talent at merck are among the company's top priorities. nevertheless, employee-related risks that affect business activities are likely, even though their impact is difficult to assess. merck rates this as a medium risk." merck kgaa further reported with respect to its pharma division, merck serono: "over 80% of the merck serono senior management positions replaced since 2011 ." novel technologies tecemotide is based on novel technologies, which may raise new regulatory issues that could delay or complicate regulatory approval. additionally, as of 2013, the fda had approved for commercial sale in the united states only one active vaccine designed to stimulate an immune response against cancer. consequently, there is limited precedent for the successful development or commercialization of products based on these technologies in this area. manufacture merck kgaa currently relies on third-party manufacturers to supply the product candidate: