15 cases of clinical trial failure published in the year! Give up or die?

Recently, fiercepharma has taken stock of 15 failed clinical trials in 2019< br / > for new drug investment, the failure of such clinical trials not only consumes a lot of investment resources and business opportunities, but also seriously affects the future of the R & D technology platform or the entire pharmaceutical enterpriseBased on the perspective of patients, fierce Pharma focuses on clinical trials that miss the pipeline of landmark therapy or breakthrough clinical progress in the field of indications not approved by relevant therapies< br / > in this inventory, on the whole, the indications of these failed clinical trials include malignant brain cancer, Alzheimer's disease and nonalcoholic steatohepatitisAs we all know, it is very challenging to develop new drugs in these treatment fieldsIn addition, the treatment for heart failure has made some progress in the past few years, but this year, two drugs under development failed to effectively alleviate the problem of drug resistance< br / > at the company level, both pharmaceutical giants and small-scale pharmaceutical enterprises are involvedFor example, there are three clinical trials involving Novartis, and two trials involving Albright and Baijian / WeicaiIn addition, from a technical point of view, these unsuccessful clinical trials cover from small molecules to biological agents, vaccines, gene therapy, gene editing and other technologiesIn addition, the inventory also encountered a special case, the drugs that had been cancelled earlier this year later miraculously returned< br / >< br / > on May 17, eberver announced that the phase III research project of the antibody coupling drug depatuxizumab mafodotin (depatux-m) was stopped< br / > depatux-m is a pipeline introduced by Aberdeen from Seattle geneticsIts main development indication is glioblastoma (GBM)It was awarded orphan drug qualification by EMA and FDA in 2014GBM is the most common and aggressive type of malignant primary brain tumorThe treatment options for GBM include surgical resection, chemotherapy, radiotherapy and immunotherapy However, for patients, the treatment prospects are still bleak, the average survival time is only 12-18 months, and the survival rate after diagnosis is only 5% < br / > in the past, there were many layouts for the development of new drugs to treat GBM, but almost all of them failed Avastin, Roche's VEGF inhibitor, is one of the few targeted drugs approved by FDA for the treatment of GBM < br / > the intellince-1 study was conducted jointly by Aberdeen and the RTOG foundation, an independent non-profit cancer research organization, with a primary end point of total survival In this study, GBM patients who had just been diagnosed with high EGFR concentration were selected as the subjects to confirm the efficacy and safety of depatux-m The interim analysis results disclosed by intellince-1 were based primarily on data from 639 patients, but the study was discontinued because patients who received depatux-m compared with placebo did not benefit from survival < br / > 02 Elenbcestat < br / > indication: Alzheimer's disease < br / > Company: Baijian and Weicai < br / > according to the recommendation of the safety supervision committee, 2100 patients with early Alzheimer's disease participated in two trials of mission AD1 and ad2, which should be stopped because the risk is greater than the benefit At the same time, the long-term observation part of phase II clinical study 202 of this product was stopped < br / > like other entrants, elenbcestat's mechanism of action is to use β - amyloid lyase (bace) inhibitors to prevent Alzheimer's disease, which ended in failure Previously, other bace inhibitors were put on hold mainly due to safety and effectiveness issues Relevant statistics show that five bace inhibitors have failed in the clinical trials in the middle and late stage, including Novartis and cnp520 terminated by Amgen < br / > it is reported that elenbcestat's suspension of this study is mainly due to the existence of "adverse risk-benefit ratio" from the clinical data of mission AD1, so safety may become the main factor again < br / > Baijian and Weicai decided to retain the research and development of an Alzheimer's drug ban2401 temporarily, which is currently in phase III clinical practice In addition, in November this year, Baijian and Weicai announced that after communicating with FDA, Baijian plans to apply for the listing of aducanumab, an experimental therapeutic drug for early Alzheimer's disease After the announcement of the news, Baijian's share price rose by more than 30% < br / > 03, ericasan < br / > indications: nonalcoholic steatohepatitis < br / > Company: Novartis, conatus < br / > in recent years, drug research and development related to nonalcoholic steatohepatitis (NASH) has become an important focus, and Nash is expected to affect nearly 1 billion patients worldwide Although there are several research and development pipelines in progress, the indication therapy has proved to be a tough challenge According to the public information, no drug has been approved for NASH treatment so far < br / > on June 25, Novartis and conatus jointly announced that enricore-lf, a phase II B study to evaluate emricasan's treatment of Nash, failed to reach the primary end point The encore-lf trial included 217 patients who received emricasan or placebo at least 5 or 25 mg twice daily for 48 weeks However, the results showed that encore-lf could not reach the primary end point This study was conducted in patients with decompensated Nash cirrhosis and showed no significant improvement in event free survival compared with placebo < br / > as early as December 2016, Novartis reached a cooperation with conatus, a pharmaceutical company, and paid $50 million in advance to obtain the potential rights of emricasan The failure of this clinical trial not only affected the cooperation between the two sides, but also conatus had to lay off 40% of its staff, suspended the research and development of cts-2090, a pre clinical Caspase-1 inhibitor, and hired Oppenheimer, a financial services company, to seek strategies to solve the problem of investor returns It is estimated that by the end of 2019, conatus's cash or current assets may be only US $10 million to US $15 million, which is very urgent < br / > 04, entresto < br / > indications: heart failure with preserved ejection fraction (HFPEF) < br / > Company: Novartis < br / > entresto was approved to treat heart failure with preserved ejection fraction in 2015 Because the test data published last year showed that it significantly reduced the risk of death and hospitalization, the sales increased greatly, and broke through the $1 billion mark < br / > entresto is expected to treat HFPEF HFPEF is a kind of heterogeneous heart failure without drug approval, accounting for almost half of all cases of heart failure, which is more common in women and the elderly According to relevant forecasts, once successful in the field of HFPEF treatment, it will cover 13 million patients around the world < br / > however, the paragon HF trial of entresto for HFPEF published in July did not meet the expectation The data showed that there was no significant difference in the composite primary end point of reducing cardiovascular death and overall heart failure hospitalization, but the overall evidence showed the potential clinical value of entresto Previously, Novartis had high hopes for entresto, with sales of the drug expected to peak at $5 billion < br / > however, Novartis did not give up expanding the use of entresto At the American Heart Association Conference held in November, Novartis reported further research data on paragon-hf, and announced another paragon-hf research trial, which will have a profound impact on some specific patients These patients included women, patients with structural changes in the left ventricle, and patients with a lower ejection fraction range Novartis said it would submit new data to relevant review agencies around the world to determine entresto's next research in the field of HFPEF treatment < br / > 05, fevipiprant < br / > indications: allergic asthma < br / > Company: Novartis < br / > recently, Novartis announced the latest results of key global phase III clinical research of new asthma drug fevipiprant Fevipiprant, an oral DP2 receptor antagonist, failed to improve lung function in patients with allergic asthma in both trials < br / > fevipiprant is regarded as a potential heavyweight drug of Novartis Early trials show positive results, which can improve patients' symptoms and lung function, inhibit inflammation, and even help to reverse the airway of allergic asthma patients caused by allergens such as pollen, dust mite or mold < br / > despite the prospect of fevipiprant in the field of allergic asthma treatment, two phase III clinical studies showed that fevipiprant failed to improve lung function with FEV1 as the detection index compared with placebo, and both trials involved uncontrolled asthma patients The results of a phase IIB trial show that the drug is the first to reduce the quality of airway smooth muscle and may reduce the use of high-dose sterol in patients < br / > it is not a case that the results of fevipiprant clinical trials fail to meet the expectations Previously, DP2 antagonists of AstraZeneca, actalon and Amgen also failed in the clinical trials However, Novartis is still conducting two clinical trials of fevipiprant for the deterioration of moderate to severe asthma, and the results are expected to be released next year Indications: glioblastoma (GBM) < br / > Company: BMS < br / > in 2019, the pharmaceutical industry is still seeking new therapies for glioblastoma, but the failure cases from immunooncology methods further hit this expectation < br / > in September, BMS announced that its PD-1 antibody, odevo, did not reach the primary end point in the phase III clinical study of patients with newly diagnosed MGMT methylated glioblastoma multiforme (GBM) Compared with the standard treatment of temozolomide and radiotherapy, oedival did not improve PFS The overall survival of the other major end point needs further evaluation < br / > this is the third clinical setback for opdivo in the research and development of GBM drugs The results of this clinical trial also make the industry have more doubts about the prospect of immunotherapy for GBM < br / > GBM has always been a difficult field of new drug research and development In the past 15 years, FDA has not approved a new first-line GBM therapy The previously approved first-line GBM therapy is temodal of MSD, which was approved in 2005 Some scientists think that the poor results of the relevant treatment test data may be due to the scarcity of T cells in the tumor microenvironment < br / > 07, PEXA VEC < br / > indications: HCC < br / > Company: transgene, silajen < br / > the feasibility of using virus to kill cells to treat tumors has been recognized by the pharmaceutical industry Based on this therapy, Amgen imligic has been approved for the treatment of advanced melanoma in 2015 In recent months, pharmaceutical giants such as Merck, Johnson & Johnson, and Aberdeen have increased their distribution in the field of oncolytic virus therapy (OVT) < br / > however, French pharmaceutical company transgene and partner Silva Jen announced in August that they would terminate the phase III clinical trial of PEXA VEC, a tumor immunolytic drug, which was expected to be launched in 2020 in advance PEXA VEC is a kind of immunotherapy for advanced liver cancer Although PEXA VEC combined with sorafenib (sorafenib) is better than the single drug group in the treatment trial, the mid-term analysis results show that it is unlikely to prolong the survival period of patients < br / > PEXA VEC is the main candidate drug of transgene company in OVT, and the only drug of sillajen company entering the clinical development stage at present For the listed sillajen, its market value of $3 billion is mainly driven by the potential of PEXA VEC Shares in both companies fell sharply after the announcement < br / > however, it seems that silajen will continue to promote PEXA VEC, which believes that the failure of the trial is due to the imbalance in the proportion of patients receiving salvage treatment, including chemotherapy, and thus the results are biased towards the control group Transgene said last month