The latest developments in the field of therapeutic delivery, December 2020
2021; Future Science Ltd; Volume: 12; Issue: 4 Linguagem: Inglês
10.4155/tde-2021-0013
ISSN2041-6008
Autores Tópico(s)Cytokine Signaling Pathways and Interactions
ResumoTherapeutic DeliveryVol. 12, No. 4 Industry NewsFree AccessThe latest developments in the field of therapeutic delivery, December 2020Peter TimminsPeter Timmins *Author for correspondence: Tel.: +44 1484 473 102; E-mail Address: p.timmins@hud.ac.ukhttps://orcid.org/0000-0002-5840-0678Department of Pharmacy, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UKPublished Online:9 Mar 2021https://doi.org/10.4155/tde-2021-0013AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail Keywords: antibody–drug conjugatecell therapiesclinical trialsCOVID-19drug deliverygene therapymergers and acquisitionsproduct approvalsrare diseasestargeted therapeuticsBusiness newsAcquisitions, mergers, licensingBoehringer Ingelheim & NBE-TherapeuticsThe gain of a novel antibody–drug conjugate (ADC) capability through the acquisition of NBE-Therapeutics (Basel, Switzerland) was announced by Boehringer Ingelheim (Ingelheim, Germany), adding to its existing immune cell-targeting assets and enhancing the company's cancer therapeutics portfolio [1]. The NBE-Therapeutics technology platform, immune-stimulatory ADC (iADC™), brings together a tumor cell-targeted monoclonal antibody, linked to an immune-stimulatory cytotoxic anthracycline payload linked via unique enzymatic site-specific linker technology, SMAC-Technology™. The result is a less heterogenous payload distribution and improved serum stability compared to other ADC technologies [2]. The Boehringer Ingelheim Venture Fund has previously been one of the major institutional investors in NBE-Therapeutics. The acquisition also brings to Boehringer an emerging pipeline of ADCs, including the Phase I clinical asset NBE-002, an ADC targeted against ROR1, a tyrosine-protein kinase receptor expressed by various difficult-to-treat blood malignancies and solid tumors, including adenocarcinoma of the lung and triple negative breast cancer.Gilead Sciences & MYR GmbHGilead Sciences (CA, USA) and MYR GmbH (Bad Homburg, Germany) announced they had entered into a definitive agreement through which Gilead will acquire MYR. The deal brings to Gilead bulevirtide (Hepcludex™), a lipopeptide antiviral agent that binds to the sodium taurocholate transporting peptide (NTCP) on the surface of hepatocytes and inhibits cell entry by viruses that employ it to gain entry. These include hepatitis B virus (HBV) and hepatitis delta virus (HDV). HDV is a significant form of viral hepatitis with high mortality rates, fast progression to fibrosis and cirrhosis and increased risk of liver cancer. It only occurs as a co-infection with HBV. First-in-class therapy bulevirtide subcutaneous injection is already conditionally approved by the European Medicines Agency and launched in France, Germany and Austria, with launches expected in other European markets during 2021. Trials of bulevirtide added on to tenofovir disoproxil fumarate (TDF) showed significantly greater reduction in viral RNA relative to TDF-only treatment. Trials of bulevirtide monotherapy are currently in progress. Submission to the US Food and Drug Administration (FDA) is planned for the second half of the year and the US FDA have already granted Orphan Drug and Breakthrough Therapy designations for bulevirtide in chronic HDV infection which may allow for an accelerated approval [3].Lilly & Prevail TherapeuticsGene therapy company Prevail Therapeutics (NY, USA) has been acquired by Eli Lilly (IN, USA), bringing a new drug discovery and development modality to the acquirer. Prevail's adeno-associated virus-9 (AAV9) vector technology is focused on targeted treatment of neurodegenerative diseases. The lead asset PR001 is in Phase I/II clinical evaluation in patients with Parkinson's disease with GBA1 mutations and in patients with neuropathic Gaucher disease (the AAV9 vector being delivered by injection via the intra-cisterna magna). A second clinical asset is PR006 which being explored as therapy for patients with frontotemporal dementia associated with GRN mutations and the deal includes further preclinical assets with potential in Alzheimer's disease, amyotrophic lateral sclerosis (ALS) and synucleinopathies [4].Surface Oncology & GSKSurface Oncology (MA, USA) has announced an exclusive license deal with GSK (Cambridge, UK) for rights to its preclinical novel immunotherapy SRF813. The fully human IgG1 antibody targets an inhibitory protein PVRIG (CD112R) expressed on natural killer cells (NK cells) and on T cells. By binding to PVRIG on the immune system cells, SRF813 prevents it interacting with CD112 which is over expressed on tumor cells. This promotes the antitumor activity of the NK cells and the T cells. It is planned that regulatory filings will be made by GSK during 2021 to initiate Phase I trials. Funding provided through the license deal will enable Surface Oncology to further develop its other preclinical immuno-oncology candidates SRF617, SRF388 and SRF114 [5].AstraZeneca & Alexion PharmaceuticalsThe year closed out with the largest merger/acquisition financial transaction of 2020 as AstraZeneca (Cambridge, UK) and Alexion Pharmaceuticals (MA, USA) announced a definitive agreement for AstraZeneca to acquire Alexion through a deal valued at $39 billion. The acquisition is subject to the usual shareholder approvals and regulatory clearances, with an expected closure in the third quarter of 2021. The addition of Alexion's marketed products and development pipeline in complement system biology therapeutics will significantly extend AstraZeneca's scientific and commercial presence in immunology and will be further enabled through the headquartering of a dedicated rare disease unit in Boston, USA leveraging the capabilities and talent established there. Marketed products from Alexion include eculizumab (Soliris®) and ravulizumab (Ultromiris®) for the treatment of rare complement biology system diseases including paroxysmal nocturnal hemoglobinuria (PNH) and the enzyme deficiency disease therapeutics sebelipase alfa (Kanuma®) and asfotase alfa (Strensiq®). A strong rare disease therapy development expertise and a pipeline of 11 molecules ranged across preclinical to Phase III transfers with the acquisition [6].Sterling Pharma Solutions & ADC BiotechnologyADC Biotechnology (Chester, UK), a specialist in novel conjugation science for ADCs (and not to be confused with ADC Therapeutics, the Epalinges, Switzerland-based clinical stage biotech) has received a significant strategic investment from contract development and manufacturing organization (CDMO) Sterling Pharma Solutions (Cramlington, UK), with a view that Sterling will acquire ADC Biotechnology during early 2021 [7]. The conjugation chemistry from ADC Biotechnology combines well with the capability at Sterling to handle highly potent small molecule chemistry to provide a single point for outsourced work in the design and development of novel ADCs.Agios Pharmaceuticals & Servier PharmaceuticalsTo enable it to develop a singular focus on a portfolio of therapies for genetically-defined diseases, Agios Pharmaceuticals (MA, USA) has entered into an agreement to sell its entire oncology portfolio (research stage, clinical stage and commercial) to Servier (Paris, France). Servier sees the acquisition as aligning with its ambition to be a recognized player in oncology and provide targeted medicine treatments for cancer patients with currently unmet medical needs. The transaction covers ivosidenib (Tibsovo®) an approved inhibitor of isocitrate dehydrogenase (IDH, which occurs in subtypes IDH1 and IDH2) for the treatment of acute myeloid leukemia (AML) associated with a susceptible mutation of IDH1. It is also in clinical trials against IDH1-mutant cholangiocarcinoma, IDH1-mutant myelodysplastic syndrome and as part of combination therapy in newly diagnosed AML. Vorasidenib, a CNS-penetrating dual inhibitor of IDH1 and IDH2 that is currently in late stage trials for the therapy of IDH-mutant low-grade glioma, is a key part of the advanced pipeline acquired in the deal. Through the acquisition, Servier will also pick up cocommercialization and specific ongoing clinical trial responsibilities for IDH2 inhibitor enasidenib (Idhifa®, Bristol Myers Squibb). Another novel targeted oncology agent, a first-in-class methionine adenosyltransferase 2A inhibitor is in Phase I trials in genetically identified patients with non-small-cell lung and pancreatic cancers as co-therapy with taxanes. Additionally, there is a strong preclinical pipeline of potential candidates against hematological and solid tumors [8–10]. Agios will now focus on the development of mitavipat, its lead pyruvate kinase-R enzyme activator candidate in the treatment of pyruvate kinase deficiency, thalassemia, and sickle cell disease along with an early stage and preclinical pipeline of agents with potential in genetically defined diseases.Novartis & Cadent TherapeuticsNovartis (Basel, Switzerland) has announced an agreement whereby it will acquire neuroscience company Cadent Therapeutics (MA, USA). The deal covers N-methyl-D-aspartate (NMDA) receptor modulator CAD-9303, currently in Phase I trials for schizophrenia and CAD-1883, currently in Phase II trials in the treatment of movement disorders. The acquisition also buys out milestones and royalties around the prior deal between Novartis and Cadent, covering Cadent's investigational compound MIJ821, licensed by Novartis in 2015. Novartis will continue to evaluate MIJ821 in therapy of treatment resistant depression. MIJ821 acts on a subset of NMDA receptors, NR2B, as a negative allosteric modulator, producing rapid onset of action similar to ketamine, without the side effects associated with ketamine treatment [11].Sosei Heptares & GSK, Captor TherapeuticsTwo deals involving novel therapeutics against G protein-coupled receptor (GPCR) targets were announced by Sosei Heptares (Tokyo, Japan) during the month. The first, with GSK, is for the discovery and development of small molecule, orally dosed agonists of GPR35, a GPCR with a genetic association to gastrointestinal immune disorders, in particular inflammatory bowel disease [12]. The portfolio of GPR35 candidates has been produced utilizing proprietary approaches developed by Sosei, namely its StaR® (Stabilized Receptor) technology and its structure-based drug design (SBDD) platform. StaR® allows the removal of a GPCR from a cell membrane with its structure intact, enabling their direct use with their in situ structure intact in drug discovery screening [13]. The deal provides GSK immediately with an advanced preclinical compound along with a set of back up compounds. The research and preclinical development aspect will involve collaboration between the two companies, but once a clinical candidate is nominated then GSK will advance clinical development, manufacturing, and commercialization. The second deal, with Captor Therapeutics (Wroclaw, Poland and Allschwil, Switzerland) is to discover and develop novel small molecules to target degradation of specific GPCRs implicated in gastrointestinal disorders. The targeting and selective destruction of the disease-associated GCPR protein as a therapeutic approach may have efficacy and safety advantages over classical approaches using small molecule inhibitors or monoclonal antibody therapeutics. Captor will apply its Optigrade™ drug-discovery platform to optimize candidates identified by Sosei SBDD approaches. Based on their combined efforts the companies will co-own any resulting products [14].CollaborationsRelay Therapeutics & GenentechRelay Therapeutics (MA, USA) has a unique drug discovery platform, Dynamo, that can provide knowledge around protein disease target structure and protein dynamics, allowing for the identification of novel small-molecule drug candidates against genetically or clinically validated therapeutic targets that were previously intractable or inadequately addressed [15]. A candidate compound already in Phase I trials, RLY-1971 is the subject of a license and collaboration agreement between Relay and Genentech (CA, USA). In exchange for upfront and other payments to Relay, along with optional profit/cost sharing and royalties or additional payments and royalty provisions, Genentech will assume development responsibilities for RLY-1971 as mono therapy and in combination drug therapy of solid tumors. RLY-1971 targets and selectively inhibits the protein tyrosine phosphatase SHP2 resulting in the protein stabilizing in an inactive conformation. Active SHP2 acts through the RAS pathway, RAS GTPases being involved in activating cell proliferation, growth, and survival and believed to be involved in how cancer cells grow and develop resistance to other anticancer therapies. Hence SHP2 inhibition as monotherapy can itself be a pathway to cancer treatment or may be used to overcome or slow development of resistance to other agents. Genentech development plans include clinical trials of the addition of RLY-1971 to its own GDC-6036, an inhibitor of the effects of KRASG12C activity, an oncogene mutation pathway involved in driving uncontrolled cell proliferation and a factor in a number of cancers including non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC) [16].AbbVie & Frontier MedicinesThe Industry Update reviews in Therapeutic Delivery seem to be increasingly noting deals where collaborators seek to utilize novel approaches to discover small-molecule candidates that can reliably engage with therapeutic targets that had been previously difficult to access, as for example the prior paragraph shows. A further example of this is seen in the deal announced between AbbVie (IL, USA) and Frontier Medicines (CA, USA) to form a global partnership to discover and develop through to commercialization novel small-molecule therapeutics directed against E3 ligase, immunology, and oncology targets. The collaboration will utilize Frontier's chemoproteomics platform, a technology approach that has the potential to identify agents active against a broader range of protein targets compared with the more limited range of target classes regarded as being the operating space for conventional drug discovery. By looking to address immunology and oncology targets that are considered validated but have been to date inaccessible, the expectation is that medicines that are highly differentiated and efficacious will result. Frontier's chemoproteomics investigates protein activity in living cells, determining how as proteins fold and move they uncover or develop temporary molecular pockets that can be unique binding sites for novel drugs to target the protein and so modulate a disease process [17]. The deal will require AbbVie to fund research and preclinical development activities at Frontier and following successful outcomes at defined preclinical stages AbbVie will assume full responsibility for development and commercialization of the successful programs in exchange for milestone success payments to Frontier [18].Bayer AG & Atara BiotherapeuticsA collaboration deal forming a fundamental element of its new cell and gene therapy strategy (see also in the section on other business news) was announced by Bayer (Berlin, Germany). The agreement includes an exclusive worldwide license agreement with Atara Biotherapeutics (CA, USA) for mesothelin-directed CAR T-cell therapies for treatment of solid tumors. The transaction encompasses research, development and manufacturing and includes two early development candidates, ATA3271, an allogenic CAR T which is in pre IND development and ATA2271 its autologous version which has just entered Phase I clinical trials. Atara's technology involves a novel Epstein-Barr virus T-cell platform combined with CAR T approaches for mesothelin targeting claimed to offer efficacy, persistence, safety, and durability of response against high mesothelin-expressing tumors. These would include a number of aggressive solid tumors such as non-small-cell lung cancer, malignant pleural mesothelioma, ovarian cancer and pancreatic cancer. The two lead candidates' novel characteristics include immune checkpoint inhibition avoidance and a costimulatory domain on the chimeric antigen receptor to enable CAR T-cell expansion and persistence. The Atara platform is well advanced in clinical trials with the company's lead program, tabelecleucel, in Phase III development for the treatment of Epstein-Barr virus-driven post-transplant lymphoproliferative disease [19].Merck KGaA & Artios PharmaMerck KGaA (Darmstadt, Germany) has signed a collaboration agreement with Artios Pharma (Cambridge UK) to utilize the UK biotech's DNA damage repair inhibitor platform for the discovery and development of targeted oncology drugs, with exclusive rights for development and commercialization of novel compounds on up to eight targets. Artios will receive up front and near term payments along with option fees and royalty payments on sales of any commercialized entity. There are also opt-in rights for joint development and commercialization between the two collaborators [20]. All cells have DNA repair mechanisms as part of their normal function, to manage continuing cell viability and to prevent cancerous mutations in the light of continuous occurrence of damage that can arise from everyday endogenous and exogenous influences (e.g., UV light, radiation, cigarette smoke, etc.). The impairment of certain DNA damage repair mechanisms is in part responsible for the genomic instability that is associated with the development of cancer cells. Such cells are dependent on the remaining and alternative DNA repair pathways to survive and proliferate. As healthy cells are not as dependent on these alternative mechanisms, the enzymes involved in them such as the DNA nucleases being pursued by Artios – the focus of the deal with Merck KGaA – make for attractive oncology therapy targets. Artios is continuing its own programmes around other oncology therapy targets involved in DNA damage repair (DNA polymerase theta or Polθ and ATR or ataxia-telangiectasia-mutated-and-Rad3-related kinase) [21]. For Merck the deal adds to its own ongoing activity in DNA damage repair as an oncology target, for example its Phase I ATR inhibitors and its DNA-dependent protein kinase (DNA-PK) inhibitor peposertib, which is in early phase trials for the treatment of rectal cancer [22].Myovant Sciences & PfizerA collaboration to develop and commercialise relugolix, a novel, orally dosed gonadotropin-releasing hormone (GnRH) receptor antagonist, in the USA and Canada has been announced by Myovant Sciences (Basel, Switzerland) and Pfizer (NY, USA), giving Pfizer an exclusive option to commercialise the compound for oncology indications outside the US and Canada (but excluding certain Asian countries). As monotherapy, Orgovyx™ will be progressed as a treatment for advanced prostate cancer and will continue to be developed as a fixed dose combination tablet (relugolix with estradiol and norethindrone acetate). The combination tablet for uterine fibroids is currently under regulatory review in the US and in Europe and regulatory submissions for endometriosis are expected in 2021. The new treatments will represent a new option to the high unmet need in women's health as well as offering the first and only oral GnRH antagonist for men with advanced prostate cancer [23].Other business newsLexaria Bioscience DehydraTECH™ enhances antiviral oral deliveryLexaria Bioscience (BC, Canada) has announced results of animal bioavailability studies for HIV protease inhibitor darunavir and HIV non-nucleoside reverse transcriptase inhibitor efavirenz, delivered using its proprietary DehydraTECH™ oral drug-delivery technology. Statistically significant increases in extent of absorption of up to 54%, as measured by the drug plasma concentration-time plot area under the curve (AUC), was seen with a DehydraTECH formulation relative to a control formulation without the DehydraTECH technology, when dosed to rats in the fed state. With the initial positive findings Lexaria have indicated their intent to evaluate additional antivirals currently employed for HIV therapy and others that have been investigated in the treatment of SARS-CoV2 (the virus that causes COVID-19) infection [24]. The DehydraTECH drug-delivery technology employs interaction between the lipophilic drug and fatty acids (as an edible oil) prepared as a mixture which is adsorbed on to a carrier, for example a starch, and then the mixture is subjected to a dehydration process that the company suggests brings the drug and the fatty acid together at a molecular level. The final material so formed can then be incorporated into dosage forms such as tablets and capsules using conventional processing [25].Atsena Therapeutics raises funding for gene therapy developmentProceeds from a financing round raising $55 million will be used by clinical-stage gene therapy ocular disease company Atsena Therapeutics (NC, USA and MA USA) to further ongoing Phase I/II clinical trials of its investigational gene therapy for rare inherited eye disease GUCYD2D-assocaited Leber congenital amaurosis (LCA1). This is one of the commonest causes of blindness in children. The funding will also allow development of manufacturing processes for the LCA1 therapy to support Phase III clinical trials. The company will also now be able to support progression of two preclinical programmes in inherited retinal diseases and continue to advance its novel AAV vector technology which is being specifically developed to suit intravitreal and subretinal injection delivery. The delivery technology was evolved out of work at the University of Florida and was previously licensed to Sanofi before being acquired by Atsena [26,27].Exo Therapeutics advancing ExoSight™ platform towards proof-of-concept studiesAnother player in the challenging drug targets space, Exo Therapeutics (MA, USA) has announced that it has secured $25 million in financing to enable it to progress its ExoSight™ drug discovery capability in addressing novel targets known as exosites. Exo has emerged out of work in Professor David Liu's laboratory at Harvard University. Exosites are binding pockets on enzymes distal to active sites that when accessed by small-molecule potential drugs can block enzyme substrate engagement to reprogram the enzyme activity to produce a therapeutic effect. Being distinct from agents binding to the enzyme active site, exosite drugs avoid challenges of competitive binding and off target activity associated with active site and allosteric modulators. The funding is to be applied to work to advance an initial portfolio of research programmes in oncology and inflammation towards proof of concept and into the clinic, and the company is anticipating strategic partnerships with other biopharmaceutical companies to further develop exosite candidates [28].Bayer AG establishes Cell & Gene Therapy platformAs well as announcing its gene therapy license deal with Atara Biotherapeutics (see above), Bayer has announced the establishment of a Cell and Gene Therapy Platform (including expertise in research and preclinical development, pharmaceutical development, clinical development, and commercialization) as a component of its Pharmaceuticals division. Building out its presence in cell and gene therapy through internal investment as well as external collaborations and licensing deals, the new platform will add to an existing Bayer pipeline of five existing asset. The company plans to bring forward three new investigational cell and gene therapy products each year for the next 5 years [29].Opiant Pharmaceuticals receives additional funding to progress nasal nalmefene developmentOpiant Pharmaceuticals (CA, USA) has received an additional funding of up to $3.5 million from the US Biomedical Advanced Research and Development Authority (BARDA) to support ongoing development of it transnasal formulation of nalmefene (OPNT003) [30]. The novel formulation of the long-acting opioid antagonist is being developed to provide a best-in-class rescue agent for the prevention of opioid overdose deaths, the delivery route offering potential for rapid onset of action. The new funding, which brings overall BARDA financing to date up to $8.1 million and adds to a grant of $7.4 million from the US National Institute on Drug Abuse will help prosecution of a pharmacodynamic study and development work on the delivery device based on Aptar Pharma's Unit Dose System (UDS) [31]. The BARDA contract also includes the development of OPNT003 as an antidote for use in case of a chemical attack employing potent synthetic opioids, minimising mass civilian casualties. A New Drug Application (NDA) with the US FDA is anticipated by the end of the year [30].Product approvals & other regulatory newsCOVID-19 vaccines (Pfizer/BioNTech, AstraZeneca, Moderna)The Industry Update reviews through 2020 have shared news of the phenomenal response from the pharmaceutical industry to the SARS-CoV- 2 (the coronavirus that causes COVID-19) pandemic. This has included the evolution of novel vaccines, antibody therapies and antiviral drugs, emerging from preclinical activity around the start of the year through early phase clinical studies and with several moving on to the prosecution of registrational clinical trials. The last month of the year saw this remarkable progress yield success, with the authorization of three of the vaccines to combat COVID-19 being granted across several territories. The lipid nanoparticle-enabled mRNA vaccine that Pfizer (NY, USA) and BioNTech (Mainz, Germany) had partnered on was authorized in the UK, the US, Canada, the EU and Switzerland [32–36] and the Moderna (MA, USA) lipid nanoparticle mRNA vaccine was authorized in the USA and Canada [37,38]. The AstraZeneca vaccine, originally developed at the University of Oxford UK and based on the genetic material coding for the virus spike protein being delivered via a nonreplicating chimpanzee adenovirus vector (ChAdOx1), was authorized in the UK at the very end of the year [39]. In all cases, these are as yet emergency use/interim/conditional authorizations and await full formal approval which will be expected to occur in due course. Nonetheless, they all represent a remarkable point on a set of very rapid development efforts, and the several other COVID-19 investigational therapies that we have mentioned in these articles through 2020 will no doubt be following closely behind, with the prospect of a control of the global pandemic now in sight.Amivantamab infusion (Janssen)The Janssen Pharmaceutical Companies (NJ, USA), part of Johnson and Johnson, have announced submission of a Biologics License Application to the US FDA for the EGFR-MET (epidermal growth factor-mesenchymal epithelial transition factor) bispecific antibody amivantamab. They are seeking its approval for the treatment of a specific subset of patients with metastatic NSCLC, those having exon 20 insertion mutations of the EGFR gene and who have had platinum-based chemotherapy but where disease has continued to progress. The fully-human antibody targets tumors with activating and resistance EGFR and MET mutations and amplifications, shutting down the uncontrolled cell growth associated with those mutations. The gene mutations occur in 10–15% of patients with NSCLC and in 40–50% of Asian patients who have the adenocarcinoma form of NSCLC. The prognosis for these patients is worse than for other forms of the disease associated with different mutations of the gene. Companion diagnostics to identify the target patient group have been part of the development program and will be available for use with amivantamab if approved. The bispecific antibody technology employed is from a license agreement between Janssen and Genmab for the latter's DuoBody platform [40].Sotorasib tablets (Amgen)Following on from receiving Breakthrough Therapy designation for its investigational KRAS inhibitor sotorasib in the treatment of NSCLC in patients carrying a mutation of the KRAS G12C gene, Amgen (CA, USA) has submitted a New Drug Application (NDA) to the US FDA for its approval for the treatment of NSCLC in this patient group [41,42]. Patients with NSCLC carrying this gene mutation represent about 13% of sufferers in the USA, and there has been no targeted therapy to date to address the needs of those with this mutation. Sotorasib represents the first ever approved targeted therapy against the KRAS G12C mutation. Identifying effective ways to specifically attack this target, once labelled as 'undruggable,' has evolved over decades of research [43]. Sotorasib was approved based on Phase II clinical data under the FDA Real-Time Oncology Review (RTOR) process, a pilot programme looking to provide a more efficient regulatory review process to advance new safe and effective cancer treatments into use as early as possible, but with continued approval requiring submission of further confirmatory data from ongoing clinical trials.Pralsetinib capsules (Gavetro™, Blueprint Medicines)Another targeted oncology therapy in the news in December was pralsetinib (Gavetro™, Blueprint Medicines; MA USA), which received FDA approval for the treatment of advanced or metastatic thyroid cancer in patients having alterations – mutations and fusions – in RET (oncogenic rearranged during transfection) which can also drive other cancer types. Blueprint has ongoing collaboration with Genentech/Roche to develop pralsetinib in the treatment of other solid tumors and the partners had already received FDA approval for pralsetinib for the treatment of NSCLC associated with RET-alterations in September of 2020 [44]. Approximately 90% of patients with advanced medullary thyroid cancer carry RET mutations. Up to now, patients with thyroid cancer associated with
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