Advanced Accelerator Applications: Difference between revisions

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{{Short description|France-based pharmaceutical group}}

{{Infobox company

|name = Advanced Accelerator Applications

|logo =

|key_people = [[SusanneSidonie SchaffertGolombowski-Daffner]], ChairmanChairperson ofand the Board of AAAPresident

|industry = [[Pharmaceutical industry|Pharmaceuticals]]

|products = GLUSCANGluscan, DOPAVIEWDopaview, FLUOROCHOLFluorochol/AAACHOLINEAaacholine, NETSPOTNetspot, SOMAKIT TOC, CARDIOGEN-82, NEUROLITE, MIBITEC/ADAMIBI, LEUKOKITSomakit Toc

|num_employees = >6001000

|revenue = [[Euro|€]]109.3 million

|num_employees = >600

|homepage = {{URL|adacap.com}}

|foundation = {{start date|2002}}

|___location = [[Saint-Genis-Pouilly]], France

|parent = [[Novartis]]

}}

'''Advanced Accelerator Applications''' ('''AAA)''' or '''Adacap''') is a [[France]]-based [[pharmaceutical]] group, specialized in the field of [[nuclear medicine]].<ref name="AAA1">[http://www.privateequitywire.co.uk/2014/02/18/197348/advanced-accelerator-applications-completes-eur41m-fundraising PrivateEquityWire, "Advanced Accelerator Applications completes fundraising", Feb 18th, 2014]</ref>

The group operates in all three segments of nuclear medicine ([[Positron emission tomography|PET]], [[SPECT]] and [[radionuclide therapy|therapy]]) to diagnose and treat serious conditions in the fields of [[oncology]], [[neurology]], [[cardiology]], infectious and inflammatory [[diseases]].<ref name="AAA2">[http://www.ilsole24ore.com/art/impresa-e-territori/2014-03-12/dal-cern-biopark-canavese-064227.shtml?uuid=ABvohR2&fromSearch Il Sole 24 Ore, “Dal"Dal Cern and Biopark canavese”canavese", March 12th, 2014]</ref>

In late October 2017, ''[[Reuters]]'' announced that [[Novartis]] would acquire the company for $3.9 billion, paying $41 per ordinary share and $82 per American depositary share representing a 47 percent premium.<ref>{{Cite news|url=http://uk.reuters.com/article/uk-novartis-advanced-accelerator/novartis-to-buy-frances-advanced-accelerator-for-3-9-billion-idUKKBN1CZ0KM|archive-url=https://web.archive.org/web/20201205154247/https://uk.reuters.com/article/uk-novartis-advanced-accelerator/novartis-to-buy-frances-advanced-accelerator-for-3-9-billion-idUKKBN1CZ0KM|url-status=dead|archive-date=December 5, 2020|title = Novartis to buy French cancer specialist AAA for $3.9 billion|newspaper = Reuters|date = 3 November 2017|last1 = Miller|first1 = John}}</ref> On January 22, 2018, Novartis AG (NYSE: NVS) announced the successful completion of the tender offer by its subsidiary, Novartis Groupe France S.A.<ref>[{{Cite press release |title=Novartis Completes Tender Offer for Advanced Accelerator Applications |date=23 January 2018 |publisher=Novartis |url=https://www.dddmagnovartis.com/news/2018/01media-releases/novartis-completes-tender-offer-advanced-accelerator-applications''Novartis Completes Tender Offer for Advanced Accelerator Applications Jan 2018]-sa-and-announces-commencement-subsequent-offering-period}}</ref>

In late October 2017, ''[[Reuters]]'' announced that [[Novartis]] would acquire the company for $3.9 billion, paying $41 per ordinary share and $82 per American depositary share representing a 47 percent premium.<ref>http://uk.reuters.com/article/uk-novartis-advanced-accelerator/novartis-to-buy-frances-advanced-accelerator-for-3-9-billion-idUKKBN1CZ0KM</ref> On January 22, 2018, Novartis AG (NYSE: NVS) announced the successful completion of the tender offer by its subsidiary, Novartis Groupe France S.A.<ref>[https://www.dddmag.com/news/2018/01/novartis-completes-tender-offer-advanced-accelerator-applications''Novartis Completes Tender Offer for Advanced Accelerator Applications Jan 2018]</ref>

==History==

AAA was created in 2002 by Italian physicist [[Stefano Buono]] to exploit a patent from the European Organization for Nuclear Research ([[CERN]]).<ref name="AAA5">[http://www.adnkronos.com/Archivio/AdnAgenzia/2010/03/19/Economia/Ricerca-da-Rubbia-a-AAA-fisico-italiano-sfonda-con-impresa-europeaAdnkronos_135335.php AdnKronos,“" Research: from Rubbia to AAA, great success for an Italian physicist with European company”company"]. March 19th, 2010.</ref>

AAA currently has a total of 31 sites in 12 countries, including: 19 production facilities in 8 countries (in Europe and the U.S.) that manufacture targeted radioligand therapies and precision imaging radioligands, and 6 sites with R&D activity.

The group currently has 20 production and [[research & development]] facilities that manufacture both [[diagnostic]] and [[therapeutic]] Molecular Nuclear Medicine products, and over 600 employees in 13 countries (Belgium, France, Germany, Italy, Poland, Portugal, Spain, Switzerland, The Netherlands, UK, Israel, U.S. and Canada).

In October 2017, Novartis announced that it intended to acquire the company for US$3.9 billion.<ref>{{Cite web |last=Wirtschaftswoche |title=Advanced Accelerator Applications: Novartis kauft Krebsspezialisten für 3,9 Milliarden Dollar |url=https://www.wiwo.de/unternehmen/industrie/advanced-accelerator-applications-novartis-kauft-krebsspezialisten-fuer-3-9-milliarden-dollar/20520264.html |access-date=2022-08-20 |website=www.wiwo.de |date=30 October 2017 |language=de}}</ref><ref>{{Cite news |last=Larsen |first=Peter Thal |date=2017-10-30 |title=Novartis Makes a Deal That Should Go Down Easy |url=https://www.nytimes.com/2017/10/30/business/dealbook/novartis-advanced-accelerator-applications.html |access-date=2024-08-26 |work=The New York Times |language=en-US |issn=0362-4331}}</ref> The acquisition was completed in January 2018.<ref>{{Cite web |title=Novartis completes tender offer for Advanced Accelerator Applications S.A. and announces commencement of subsequent offering period |url=https://www.novartis.com/news/media-releases/novartis-completes-tender-offer-advanced-accelerator-applications-sa-and-announces-commencement-subsequent-offering-period |access-date=2024-08-26 |website=Novartis |language=en}}</ref>

AAA's Board of Directors includes Frédéric Collet, Jessica Toepfer and Susanne Schaffert.

In January 2024, AAA announced plans to expand manufacturing capabilities and build additional RLT supply facilities in Sasayama, Japan, and Haiyan, Zhejiang, China.<ref>{{Cite web |last=Staff |first=G. E. N. |date=2024-01-24 |title=Novartis Automates New Radioligand Therapy Production Plant |url=https://www.genengnews.com/topics/bioprocessing/novartis-automates-new-radioligand-therapy-production-plant/ |access-date=2024-08-26 |website=GEN - Genetic Engineering and Biotechnology News |language=en-US}}</ref>

AAA announced its full-year results for 2016, with sales of €109,3 million (+23% vs. 2015).

In August 2024, Siemens Healthineers bought the diagnostic arm of Advanced Accelerator Applications that specialises in producing radioactive chemicals used for cancer scan for more than $224 million.<ref>{{Cite web |title=Siemens Healthineers boosts cancer imaging with €200mn Novartis deal |url=https://www.ft.com/content/4a1cf48b-5d55-4e54-8ed6-018b86a6589d?accessToken=zwAAAZGNq7qSkc9KHPSLXVVOVNOO1gGLhqZYnQ.MEQCIBJEdWwU2600r3GB8rJ6-Qas9nWeZqNmDTCnUa0K_HyqAiA2aDmMEZpgsolmVHMfV60y1ifOCnpFZ0yQIokZUHPoTA&segmentId=e95a9ae7-622c-6235-5f87-51e412b47e97&shareType=enterprise&shareId=58f4a850-09e6-46b3-8a7e-bc70ee45432b |access-date=2024-08-26 |website=www.ft.com}}</ref>

==Products==

AAA has a portfolio of diagnostic and therapeutic applications and products in the fields of [[Molecular Imaging]] and [[Therapy]].

<ref name="AAA13">[{{Cite web |url=http://www.adacap.com/nuclear-medicine/glossary/ |title=Advanced Accelerator Applications Nuclear Medicine Glossary] |access-date=2015-04-15 |archive-url=https://web.archive.org/web/20150413024820/http://www.adacap.com/nuclear-medicine/glossary/ |archive-date=2015-04-13 |url-status=dead }}</ref>

The group’sgroup's portfolio of radiopharmaceuticals includes radioactive agents for [[positron emission tomography]] ([[Positron emission tomography|PET]]) imaging as well as [[single-photon emission computed tomography]] ([[SPECT]]) diagnostic products.<ref name="AAA14">[{{Cite web |url=https://www.medicaldevicedaily.com/img/MDDexample.pdf |title=Medicaldevicedaily.com, “AAA"AAA to increase clinical trials of MNM diagnostic products”products", Febr 19th, 2014] |access-date=2014-04-07 |archive-url=https://web.archive.org/web/20140408212003/https://www.medicaldevicedaily.com/img/MDDexample.pdf |archive-date=2014-04-08 |url-status=dead }}</ref>

===Lutathera===

{{see also|Peptide receptor radionuclide therapy}}

The company's lead product is LUTATHERA, a Lutetium Lu 177 dotatate <ref>[https://hemonc.org/wiki/Lutetium_Lu_177_dotatate_(Lutathera)</ref> labeled [[DOTA-TATE|somatostatin analogue peptide]],<ref>{{cite news |last1=Larsen |first1=Peter Thal |title=Novartis Makes a Deal That Should Go Down Easy |url=https://www.nytimes.com/2017/10/30/business/dealbook/novartis-advanced-accelerator-applications.html |work=The New York Times |date=30 October 2017}}</ref> a theragnostic cancer product being developed to treat certain gastro-entero [[pancreatic]] [[neuroendocrine tumors]] ([[GEP-NET]]s).<ref>{{cite web |last1=Warner |first1=Jeremy L |last2=Fitts |first2=Austin |last3=Warner |first3=Jeremy |title=Lutetium Lu 177 dotatate (Lutathera) |url=https://hemonc.org/wiki/Lutetium_Lu_177_dotatate_(Lutathera) |website=HemOnc.org |access-date=14 August 2022 |date=6 May 2021}}</ref> It selectively targets over-expressed somatostatin receptors while also giving off gamma emissions to allow physicians to visualize where in the body both the drug and the tumor are.

It was approved by the FDA in January 2018 for GEP-NET.<ref>[https://www.healio.com/hematology-oncology/gastrointestinal-cancer/news/online/%7B5e89833e-97c3-4a91-a2c8-88231a517b78%7D/fda-approves-lutathera-for-gastroenteropancreatic-neuroendocrine-tumors ''FDA approves Lutathera for gastroenteropancreatic neuroendocrine tumors'' Jan 2018]</ref>

==== Approval ====

·        Lutathera, also known as [[lutetium]] Lu 177 dotatate, is a target treatment drug for patients suffering fromwith [[Neuroendocrine tumor|GEP-NETs]].<ref name=":0">{{Cite web|url=https://www.cancer.gov/news-events/cancer-currents-blog/2018/lutathera-fda-gastrointestinal-nets|title=FDA Approves New Treatment for Neuroendocrine Tumors|website=National Cancer Institute|date=8 February 2018|language=en|access-date=2018-05-26}}</ref> Its approval for Advanced Accelerator Applications was announced on January 26, 2018, by the [[Food and Drug Administration|US Food and Drug Administration]].<ref name=":1">{{Cite web|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm594043.htm|archive-url=https://web.archive.org/web/20180128055839/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm594043.htm|url-status=dead|archive-date=January 28, 2018|title=Press Announcements - FDA approves new treatment for certain digestive tract cancers|last=Commissioner|first=Office of the|website=www.fda.gov|language=en|access-date=2018-05-26}}</ref> Lutathera is most notable as the first FDA approved peptide receptor [[radionuclide]] therapy (PRRT) to combat GEP-NETs.<ref name=":2">{{Cite web|url=https://www.novartis.com/news/media-releases/advanced-accelerator-applications-receives-fda-approval-lutatherar-treatment-gastroenteropancreatic-neuroendocrine-tumors|title=Advanced Accelerator Applications Receives FDA Approval for Lutathera® for Treatment of Gastroenteropancreatic Neuroendocrine Tumors {{!}} Novartis|website=Novartis|language=en|access-date=2018-05-26}}</ref>

===== GEP-NETs =====

·        [[Neuroendocrine tumor|GEP-NETs]] are rare groups of cancer that continue to proliferate, regardless of initial therapy treatments.<ref name=":0" /> They are present in areas affected by [[Pancreatic cancer|pancreatic]] or [[Gastrointestinalgastrointestinal cancer|gastrointestinal cancers]]s; specifically, the [[pancreas]], [[stomach]], [[intestines]], [[Large intestine|colon]] and [[rectum]].<ref name=":1" />

==== Use ====

·        Lutathera is used to combat pancreatic and gastrointestinal cancers that do not respond well to common [[Chemotherapy|chemochemotherapeutical]]<nowiki/>therapeutical treatments; namely for patients with [[somatostatin]] receptor-positive GEP-NETs.<ref name=":0" /><ref name=":1" /> These receptors are commonly found on tumors located in the [[foregut]], [[midgut]], and [[hindgut]].<ref name=":3">{{Cite web|url=https://lutathera.com/|title=For Patients - Lutathera|website=Lutathera|language=en-US|access-date=2018-05-26}}</ref>

==== Mechanism ====

·        Lutathera is a radioactive drug comprisedconsisting of a [[tyrosine]]-containing somatostatin analog Tyr3-octreotate (TATE) attached to the [[Chelation|chelating]] agent tetraazacyclododecanetetra-[[Acetic acid (medical use)|acetic acid]] (DOTA).<ref name=":4">{{Cite web|url=https://www.cancer.gov/publications/dictionaries/cancer-drug|title=NCI Drug Dictionary|website=National Cancer Institute|language=en|access-date=2018-05-26}}</ref> Attached to the [[DOTA-TATE|dotatate]] is the radioactive marker Lu-177, a [[radioisotope]].<ref name=":0" /> The dotatate binds to the GEP-NET positive somatostatin receptor cells commonly present on [[neuroendocrine]] tumors.<ref name=":0" /><ref name=":4" /> After binding to the receptor, Lutathera enters the cell and uses its radioactive property to damage DNA.<ref name=":0" /> This mechanism effectively triggers [[apoptosis]] of cancerous tumor cells. As a result, studies found that 16% of patients being treated with Lutathera experienced either complete or partial tumor shrinkage.<ref name=":0" />

==== Studies ====

·        FDA approval of Lutathera was ultimately supported by two clinical studies.<ref name=":1" /> NETTER-1, a Phase 3 study, was a randomized [[clinical trial]] which included patients with a severe form of somatostatin receptor-positive NETs.<ref name=":0" /><ref name=":2" /> The study compared Lutathera treatment with a standard dose of [[octreotide]]<nowiki/>d LAR against a high-dose of octreotide LAR.<ref name=":0" /> Researchers measured tumor growth after the course of the treatment, also known as [[progression-free survival]].<ref name=":1" /> The study concluded that patients who were treated with Lutathera lived substantially longer compared to those who only received the octreotide treatment.<ref name=":0" /> They experienced a 79% reduction in death and cancer progression.<ref name=":2" />

·        The Netherlands study gathered several patients with somatostatin receptor-positive tumors, including patients with GEP-NETs.<ref name=":0" /> The study found that 16% of patients with GEP-NETs, who were treated with Lutathera, experienced complete or partial tumor shrinkage.<ref name=":0" /> As a result, a pre-planned interim overall survival analysis found that Lutathera treatment lead to a 48% reduction in risk of death.<ref name=":2" />

==== Common Grade 3-4 Adverse Reactions<ref name=":0" /><ref name=":1" /><ref name=":2" /><ref name=":3" /> ====

{| class="wikitable"

|Common problems

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|-

|

|RenalKidney failure

|2%

|-

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|

|}

<ref name=":0" /><ref name=":1" /><ref name=":2" /><ref name=":3" />

==== Advances ====

·        Lutathera is a major technological advancement for the detection of tumors. [[Diagnostic imaging]] that relies on dotatates can now rely on Lutathera to locate somatostatin receptor-positive tumors by tagging them with its radioactive component.<ref name=":0" /> This tagging of tumors will allow them to become more visible during [[PET radiotracer|positron emission tomography]] (PET) scans.<ref name=":0" /> With LU-177 dotatates, more somatostatin receptor-positive GEP-NET patients can be identified for treatment of the disease.<ref name=":0" />

=== LysaKare ===

LysaKare received a marketing authorisation valid throughout the EU on 25 July 2019.<ref name="LysaKare EPAR">{{cite web | title=LysaKare EPAR | website=[[European Medicines Agency]] (EMA) | date=26 August 2024 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/lysakare | access-date=26 August 2024 }}{{PD-notice}}</ref>

LysaKare protect the kidneys from radiation damage during cancer treatment with a radioactive medicine called lutetium (177Lu) oxodotreotide. LysaKare is for use in adults and contains the active substances arginine and lysine.<ref name="LysaKare EPAR"/>

==Pipeline==

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AAA has a broad pipeline of products in development, including several theragnostic pairings for oncology indications.

NETSPOT and SomaKit TOC are novel kits for radiolabeling somatostatin analogue peptides to help diagnose somatostatin receptor-positive NET lesions. Each kit has received orphan drug designation from both the EMA and the FDA.<ref name="AAA17">[http://www.devicespace.com/News/advanced-accelerator-applications-receives-orphan/325871 Devicespace.com, “Advanced"Advanced Accelerator Applications Receives Orphan Drug Designation From FDA And European Medicines Agency For Gallium-68 DOTATATE For Use In Patients With Gastro-Entero-Pancreatic Neuroendocrine Tumors”Tumors"] {{Webarchive|url=https://web.archive.org/web/20140408234004/http://www.devicespace.com/News/advanced-accelerator-applications-receives-orphan/325871 |date=2014-04-08 }}. 3 March 2014.</ref><ref name="AAA18">[http://www.news-medical.net/news/20140304/AAA-gets-orphan-drug-designation-status-for-radiopharmaceutical-Gallium-68-DOTATATE.aspx News Medical, "AAA gets orphan drug designation status for radiopharmaceutical, Gallium-68 DOTATATE"]. 4 March 2014.</ref>

99MTc-rhAnnexin V-128, a [[SPECT]] investigational candidate for the diagnosis and assessment of apoptotic and necrotic processes, which are present in a number of pathological conditions in oncology and cardiovascular disease, as well as in autoimmune disorders. 99MTc-rhAnnexin V-128 is currently in a Phase I/II trial for the diagnosis of rheumatoid arthritis and ankylosing spondylitis, as well as several Phase II studies in cardiovascular, cardio-oncology, and pulmonary indications.

177LuPSMA¹⁷⁷Lu-R2PSMA-617 and 68GaPSMA⁶⁸Ga-PSMA-R2617 are in development to treat, image, monitor and stage prostate cancer. PSMA-R2617 is a ligand of Prostate[[glutamate carboxypeptidase II|prostate-Specificspecific Membranemembrane Antigenantigen]] (PSMA), expressed on the majority of prostate tumor cells. 177LuPSMA¹⁷⁷Lu-R2PSMA-617 also known as [[Lutetium (177lu) vipivotide tetraxetan|lutetium (¹⁷⁷Lu) vipivotide tetraxetan]] is being developed to treat prostate cancer andby 68GaPSMAbinding to PSMA-R2617. isIn underJune development2021 asit itswas granted a complementary[[breakthrough diagnostictherapy]] candidatedesignation.<ref>{{cite web

|url=https://www.pharmatimes.com/news/novartis_radioligand_therapy_granted_us_breakthrough_therapy_designation_1371903

|title=Novartis' radioligand therapy granted US Breakthrough Therapy Designation

|first=Lucy|last=Parsons|date=2021-06-21|website=PharmaTimes Online|access-date=2021-07-10}}</ref> ⁶⁸Ga-PSMA-617 is under development as a complementary diagnostic candidate.

CTT1057 is an 18F-labeled investigational diagnostic candidate in development for PET imaging of prostate cancer. CTT1057 is a phosphoramidate-based peptide, which specifically binds to Prostate-Specific Membrane Antigen (PSMA), expressed on the majority of prostate tumor cells.

177LuNeoBOMB1 and 68GaNeoBOMB1 are new generation antagonist [[bombesin]] analogs in development to treat, image, monitor and stage gastrin-releasing peptide receptor (GRPR)-expressing malignancies, such as such as [[gastrointestinal stromal tumors]] (GIST), prostate cancer and breast cancer. 177LuNeoBOMB1 is a therapeutic candidate and 68GaNeoBOMB1 is its complementary diagnostic candidate.

==Millburn site==

In 2016, AAA opened a light manufacturing and distribution site in Millburn, NJ, a residential town in North Jersey.<ref name="AAA24">Danielle Desisto. [http://archive.northjersey.com/news/drug-manufacturer-that-raised-ire-opens-1.1638411 "Millburn manufacturing site safely produces cancer-fighting drug"].</ref> When the site was first purchased, it caused substantial concerns among local residents.<ref name="AAA19">[http://archive.northjersey.com/news/business/radioactive-medicine-site-causes-concerns-1.1327213 "Concerns raised about proposed cancer drug factory in Millburn"]</ref> Per the requests of Millburn Residents, the Township Committee hired a nuclear/radiology expert to re-assess the appropriateness of opening a radioactive manufacturing site in the residential area.<ref name="AAA20">Cecilia Levine. [http://theitem.northjersey.com/epaper/viewer.aspx "Nuclear meds expert hired"]. ''The Record''. 7 May 2015.</ref> The expert concluded that the proposed operations at AAA are safe and pose no hazard to the citizens of Millburn.<ref name="AAA22">Jonathan Sym. [https://www.tapinto.net/towns/millburn-slash-short-hills/categories/millburn-slash-short-hills-top-stories/articles/advanced-accelerator-application-investigation-re "Advanced Accelerator Application Investigation Results: Risks Are “Close"Close To Zero Without Being Zero”Zero" Says Expert". ''Tap Into Millburn/Short Hills''. 18 February 2016.]</ref><ref name="AAA23">Harry Trumbore. [http://www.northjersey.com/news/drug-factory-report-it-s-safe-1.1509182 "Expert says radiopharmaceutical factory proposed for Millburn is safe"] . 11 February 2016</ref>

==References==

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[[Category:French companies established in 2002]]

[[Category:Pharmaceutical companies established in 2002]]

[[Category:Companies based in Auvergne-Rhône-Alpes]]