Unlucky 13 Atabecestat Top Clinical Trial Failures of 2018 ...€¦ · BROADEN YOUR PERSPECTIVE See...
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A–List Janssen (Johnson & Johnson) Alzheimer’s disease BACE inhibitor Atabecestat (JNJ-54861911) Janssen halted clinical development of Atabecestat, ending a Phase IIb/III trial and a Phase II European long-term safety study, after citing “serious” elevations of liver enzymes in some study participants who received the drug. 1 Boehringer Ingelheim Alzheimer’s disease PDE9 inhibitor BI 409306 Boehringer Ingelheim shifted BI 409306’s development focus to ongoing schizophrenia studies after missing efficacy endpoints in two Phase II trials in patients with cognitive impairment and memory dysfunction in Alzheimer’s and schizophrenia. 4 Sosei Group and Allergan Lewy body dementia Muscarinic M1 receptor agonist HTL0018318 The companies said Phase II studies in Lewy body dementia and other dementias, including Alzheimer’s, would be delayed at least 6 months. The companies cited the need to investigate an unexpected toxicology finding that occured in a single animal study involving nonhuman primates. 7 Merrimack Pharmaceuticals Pancreatic cancer Tetravalent monoclonal antibody MM-141 (istiratumab) Merrimack scrapped MM-141 after missing primary and secondary endpoints in the Phase II CARRIE trial, assessing the drug plus nab-paclitaxel in patients with previously untreated metastatic pancreatic cancer and high serum levels of free insulin-like growth factor-1. 10 Vectura Group Asthma Drug-device combo with jet nebulizer VR475 (nebulized budesonide) Vectura ended VR475 development in November after it failed a Phase III trial in adults and adoles- cents with severe uncontrolled asthma. Vectura added VR475 to its pipeline in 2014 by acquiring Activaero for €130M ($147.6M). 13 Dermira Acne vulgaris Topical sebum inhibitor Olumacostat glasaretil Dermira effectively scrapped olumacostat glasaretil after it failed to reduce lesion counts or show 2+ grade IGA improvement in two Phase III trials. The drug was once projected to generate $250M in annual sales. 11 Merck & Co. Prodromal Alzheimer’s disease BACE1 inhibitor Verubecestat (MK-8931) Merck & Co. dropped verubecestat from its late-stage pipeline after the drug failed the Phase III APECS study in February 2018—the drug’s second late-stage failure. The first came in February 2017 in the EPOCH study. 12 Advaxis Cervical + head and neck cancer Targeted Lm-based immunotherapy Axalimogene filolisbac A Phase I/II combination trial with AstraZeneca’s Imfinzi® was halted in March after a patient death, then resumed in July after C-level overhaul. In November, Advaxis said it would halt enrollment in the combination trial to maximize the efficient use of clinical funding resources. 2 Edge Therapeutics Aneurysmal subarachnoid hemorrhage Bioabsorbable microparticle EG-1962 (nimodipine microparticles) Edge ended the Phase III NEWTON2 study after concluding EG-1962 was unlikely to meet the primary endpoint. Edge reviewed strategic alternatives, resulting in its planned reverse- merger with PDS Biotechnology, expected to close in Q1 2019. 5 Neurocrine Biosciences Tourette syndrome Selective VMAT2 inhibitor Ingrezza® (valbenazine) Neurocrine began 2019 assessing Ingrezza’s future in Tourette syndrome after its third trial failure in that indication, missing the primary endpoint in the Phase IIb T-Force GOLD Study. Ingrezza generated an estimated $409M in the treatment of tardive dyskinesia. 8 vTv Therapeutics Alzheimer’s disease RAGE inhibitor Azeliragon (TTP488) Shares plunged 71% after vTv halted azeliragon studies following an initial readout failure in Part A of the Phase III STEADFAST study. However vTv identified a subpopulation (Alzheimer’s patients with type 2 diabetes) showing statistically significant benefit. 3 Incyte Unresectable or metastatic melanoma IDO1 inhibitor Epacadostat (INCB024360) Incyte downsized its epacadostat clinical program after a combination with Merck & Co.’s Keytruda® (pembrolizumab) failed the Phase III ECHO-301/ KEYNOTE-252 trial. Two pivotal lung cancer trials of the combo were converted to Phase II studies. 6 Auris Medical Holding Acute inner ear tinnitus NMDA receptor antagonist Keyzilen® (AM-101) Auris has been weighing Keyzilen’s future since March 2018, when the drug missed its primary endpoint in the TACTT3 trial of significant Tinnitus Functional Score improvement vs. placebo— Keyzilen’s second Phase III failure in 19 months. 9 Unlucky 13 Top Clinical Trial Failures of 2018 Each drug candidate is listed alphabetically. Also shown is each drug’s sponsor(s), the indication for which the drug failed, the type of drug, and a brief account of how the drug failed.
Transcript of Unlucky 13 Atabecestat Top Clinical Trial Failures of 2018 ...€¦ · BROADEN YOUR PERSPECTIVE See...
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A–List
Janssen (Johnson & Johnson)Alzheimer’s diseaseBACE inhibitor
Atabecestat (JNJ-54861911)
Janssen halted clinical development of Atabecestat, ending a Phase IIb/III trial and a Phase II European long-term safety study, after citing “serious” elevations of liver enzymes in some study participants who received the drug.
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Boehringer IngelheimAlzheimer’s diseasePDE9 inhibitor
BI 409306
Boehringer Ingelheim shifted BI 409306’s development focus to ongoing schizophrenia studies after missing efficacy endpoints in two Phase II trials in patients with cognitive impairment and memory dysfunction in Alzheimer’s and schizophrenia.
4
Sosei Group and AllerganLewy body dementiaMuscarinic M1 receptor agonist
HTL0018318
The companies said Phase II studies in Lewy body dementia and other dementias, including Alzheimer’s, would be delayed at least 6 months. The companies cited the need to investigate an unexpected toxicology finding that occured in a single animal study involving nonhuman primates.
7
Merrimack PharmaceuticalsPancreatic cancerTetravalent monoclonal antibody
MM-141 (istiratumab)
Merrimack scrapped MM-141 after missing primary and secondary endpoints in the Phase II CARRIE trial, assessing the drug plus nab-paclitaxel in patients with previously untreated metastatic pancreatic cancer and high serum levels of free insulin-like growth factor-1.
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Vectura GroupAsthmaDrug-device combo with jet nebulizer
VR475 (nebulized budesonide)
Vectura ended VR475 development in November after it failed a Phase III trial in adults and adoles-cents with severe uncontrolled asthma. Vectura added VR475 to its pipeline in 2014 by acquiring Activaero for €130M ($147.6M).
13DermiraAcne vulgarisTopical sebum inhibitor
Olumacostat glasaretil
Dermira effectively scrapped olumacostat glasaretil after it failed to reduce lesion counts or show 2+ grade IGA improvement in two Phase III trials. The drug was once projected to generate $250M in annual sales.
11 Merck & Co.Prodromal Alzheimer’s diseaseBACE1 inhibitor
Verubecestat (MK-8931)
Merck & Co. dropped verubecestat from its late-stage pipeline after the drug failed the Phase III APECS study in February 2018—the drug’s second late-stage failure. The first came in February 2017 in the EPOCH study.
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AdvaxisCervical + head and neck cancerTargeted Lm-based immunotherapy
Axalimogene filolisbac
A Phase I/II combination trial with AstraZeneca’s Imfinzi® was halted in March after a patient death, then resumed in July after C-level overhaul. In November, Advaxis said it would halt enrollment in the combination trial to maximize the efficient use of clinical funding resources.
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Edge TherapeuticsAneurysmal subarachnoid hemorrhage Bioabsorbable microparticle
EG-1962 (nimodipine microparticles)
Edge ended the Phase III NEWTON2 study after concluding EG-1962 was unlikely to meet the primary endpoint. Edge reviewed strategic alternatives, resulting in its planned reverse- merger with PDS Biotechnology, expected to close in Q1 2019.
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Neurocrine BiosciencesTourette syndromeSelective VMAT2 inhibitor
Ingrezza® (valbenazine)
Neurocrine began 2019 assessing Ingrezza’s future in Tourette syndrome after its third trial failure in that indication, missing the primary endpoint in the Phase IIb T-Force GOLD Study. Ingrezza generated an estimated $409M in the treatment of tardive dyskinesia.
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vTv TherapeuticsAlzheimer’s diseaseRAGE inhibitor
Azeliragon (TTP488)
Shares plunged 71% after vTv halted azeliragon studies following an initial readout failure in Part A of the Phase III STEADFAST study. However vTv identified a subpopulation (Alzheimer’s patients with type 2 diabetes) showing statistically significant benefit.
3
IncyteUnresectable or metastatic melanoma IDO1 inhibitor
Epacadostat (INCB024360)
Incyte downsized its epacadostat clinical program after a combination with Merck & Co.’s Keytruda® (pembrolizumab) failed the Phase III ECHO-301/KEYNOTE-252 trial. Two pivotal lung cancer trials of the combo were converted to Phase II studies.
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Auris Medical HoldingAcute inner ear tinnitusNMDA receptor antagonist
Keyzilen® (AM-101)
Auris has been weighing Keyzilen’s future since March 2018, when the drug missed its primary endpoint in the TACTT3 trial of significant Tinnitus Functional Score improvement vs. placebo—Keyzilen’s second Phase III failure in 19 months.
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Unlucky 13Top Clinical Trial Failures of 2018
Each drug candidate is listed alphabetically. Also shown is each drug’s sponsor(s), the indication for which the drug failed, the type of drug, and a brief account of how the drug failed.
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