Tecemotide


Tecemotide is a synthetic lipopeptide that is used as antigen in an investigational therapeutic cancer 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 then to a rejection of tumor tissue expressing the MUC1 antigen.

Collaboration

Tecemotide was developed – until Clinical trial phase II – by the Canadian biotech company Biomira Inc., which changed in 2007 the company name to Oncothyreon Inc. Oncothyreon is now located in Seattle, Washington, USA. Reformed to SGEN after M&A in March 2018.
In 2001, Merck KGaA, Darmstadt, Germany, entered into a collaboration and supply agreement with Oncothyreon. In 2007, Merck KGaA acquired the exclusive worldwide marketing rights from Oncothyreon and Merck KGaA is since then 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 Co., Ltd., Japan, acquired a co-development and co-marketing license for Tecemotide in Japan and Merck KGaA received an upfront payment of 5 million Euros.

Structure

The antigen: Tecemotide

3-O-Deacyl-4’-monophosphoryl lipid A is the adjuvant in the cancer vaccine. MPL is a derivative of the lipid A molecule found in the membrane of Gram-negative bacteria. MPL is also used as adjuvant in other vaccines, e.g. Cervarix which is a vaccine against certain types of cancer-causing human papillomavirus.
Function:
Lipids:
Function:
The antigen tecemotide is anchored — together with the adjuvant MPL — in the membrane of the liposome. This liposomal formulation is the investigational therapeutic cancer vaccine. 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 sorted by Primary Completion Date:

Overview of completed trials

Overview of completed tecemotide trials where results have been published, sorted by Primary Completion Date:
IDPhaseIndicationStartPrimary
Completion
Date		Summary 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 1, 2NSCLCDecember 2008May 2014Primary endpoint and secondary endpoints not met. Subgroup analysis not favorable

Merck KGaA discontinues the development of tecemotide in NSCLC (Non-small cell lung cancer)

On August 18, 2014, Oncothyreon and finally on September 12, 2014, also Merck KGaA informed that a randomized Phase 1/2 study, EMR 63325–009, of tecemotide compared to 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. 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.
It remains unclear from Merck's press release what happens with:
Risks that could affect the further development of tecemotide published in the annual reports of Oncothyreon and Merck KGaA :

Risks related to efficacy

As published so far, primary end points have not been met in the clinical studies and tecemotide has shown only treatment effects in statistical analyses of certain subgroups.

Risks related to patent situation

Oncothyreon's patent protection for tecemotide in the U.S. will expire in 2018.

Risks related to human resources

Merck KGaA is reporting 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 is further reporting with respect to its pharma division Merck Serono: "Over 80 % of the Merck Serono senior management positions replaced since 2011 ."

Risks related to novel technologies

Tecemotide is based on novel technologies, which may raise new regulatory issues that could delay or make regulatory approval more difficult. Additionally, to date, the FDA has 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.

Risks related to manufacture

Merck KGaA currently relies on third-party manufacturers to supply the product candidate: On Baxter International Inc., for the manufacture of tecemotide, and on GlaxoSmithKline plc for the manufacture of the adjuvant in tecemotide called monophosphoryl lipid A. If tecemotide is not approved until 2015, GSK may terminate its obligation to supply the adjuvant MPL. In this case, Oncothyreon would retain the necessary licenses from GSK required to have the adjuvant MPL manufactured, but the transfer of the process to a third party would delay the development and commercialization of tecemotide.
GSK is developing the MAGE A3 vaccine in Phase 3, a direct competitor to tecemotide.

Risks related to competition

Competition in NSCLC: There are currently two products approved as maintenance therapy following treatment of inoperable locoregional Stage III NSCLC with induction chemotherapy, Tarceva, a targeted small molecule from Genentech, Inc., a member of the Roche Group, and Alimta, a chemotherapeutic from Eli Lilly and Company. Tecemotide has not been tested in combination with or in comparison to these products. It is possible that other existing or new agents will be approved for this indication. In addition, there are at least two vaccines in development for the treatment of NSCLC, including GSK's MAGE A3 vaccine in Phase 3 and Transgene's TG-4010 in Phase 2/3. TG-4010 also targets MUC1, although using technology different from tecemotide.

Drug development cost

The cost spent for the tecemotide development – beginning in the late 1990s – have not been published in detail by the companies Biomira/Oncothyreon, Merck KGaA and Ono Pharmaceutical. Additionally, the estimation of full cost of bringing a new drug to market – from discovery through clinical trials to approval – is complex and controversial.
However, a cautious estimate of the tecmotide development cost spent until 2014 ranges from 300 to 500 million Euros.

History

DateEvent
May 1998Biomira files a BLP25 patent
May 2001Biomira licenses BLP25 to Merck KGaA
Aug 2001Biomira publishes results of a Phase I study of the BLP25
Mar 2006Results of the Phase IIb Study : Subgroup analysis favorable
Aug 2007Merck KGaA acquires worldwide marketing rights for tecemotide from Oncothyreon and will be entirely responsible for the further clinical development of tecemotide
Sep 2007Biomira changes company name to Oncothyreon
Dec 2008Merck KGaA acquires manufacturing rights for tecemotide from Oncothyreon
Dec 2009INSPIRE study started. Estimated primary completion date is May 2020
Oct 2011Ono Pharmaceutical acquires a co-development and co-marketing license for tecemotide in Japan
Dec 2012Results of the START study : Primary endpoint not met. Subgroup analysis favorable
Mar 2014START2 study started. Estimated primary completion date is July 2018
Aug 2014Results of the Japan study : Primary endpoint and secondary endpoints not met. Subgroup analysis not favorable
Sep 2014Merck KGaA terminates the NSCLC development