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    Home > Medical News > Medical World News > Top 15 most "down" clinical data in 2019 (I)

    Top 15 most "down" clinical data in 2019 (I)

    • Last Update: 2019-12-17
    • Source: Internet
    • Author: User
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    Compile newborn Clinical trials are the most important and expensive step in the market of new drugs It is no secret that the probability of a project from the first human trial to the market is very low Of course, once a project enters the critical trial phase, the probability of success will increase But with millions or even billions of dollars invested each year, many new drug projects fail at the last checkpoint Fierce bio tech recently released top 15 clinical failures in 2019, which have a significant impact on pharmaceutical companies and the patient groups they treat For pharmaceutical companies, it means not only wasting investment and missing business opportunities, but also, in some cases, raising concerns about the company's treatment platform and even the future fate of the company At the patient level, the list focuses on clinical trials that fail to meet targets or could otherwise provide clinically meaningful therapeutic progress in diseases for which therapeutic drugs have not been approved The list includes trials of invasive brain cancer, Alzheimer's disease (AD) and nonalcoholic steatohepatitis (NASH), the most difficult diseases in drug development At the same time, heart failure has made some progress in the past few years, but some types of heart failure are still resistant to treatment In this context, two drugs have been listed this year The list covers a range of companies, large and small, but some are more prominent For example, Novartis accounted for three items, and Alberta and Bojian / Weicai accounted for two items respectively The list also covers a range of technologies, from small molecules to biological agents, vaccines, gene therapy, gene editing drugs, etc It's worth noting that there is a drug in the list with quotation marks added for its clinical failure The drug was declared a failure earlier this year, but it made a miraculous comeback Don't doubt yourself Xiaobian believes you can guess which drug it is! Here are the top 8 items in the top 15 list, each of which gives a brief introduction to the drugs, indications for treatment, results and effects of failed trials High grade glioma (HGG) is one of the most difficult tumors to treat Depatux-m is one of at least three drugs that failed to reach the standard in the clinical trials of this highly invasive brain cancer in 2019 In the newly diagnosed patients with glioblastoma multiforme (GBM), depatux-m failed in the phase III interlance-1 trial GBM is a subclass of HGG, derived from brain cells called astrocytes, and is recognized as the fastest growing and most malignant type At present, the treatment of GBM is surgery and chemotherapy / radiotherapy, but the prognosis of patients is very poor, the average survival time is 12-18 months, only 5% of patients are still alive 5 years after diagnosis In the past years, efforts to develop new drugs for GBM have almost failed Roche's heavyweight product Avastin is one of the few targeted drugs approved by FDA to treat this cancer Depatux-m is an anti EGFR ADC targeting epidermal growth factor receptor (EGFR) This kind of drug is stable in the blood Once it enters the target cancer cells, it releases strong cytotoxic agents In the past few years, EGFR inhibitors have rarely been successful in GBM trials According to eberver, by linking EGFR targeted antibodies to chemotherapy payloads, it will help to succeed in the event of other EGFR drug failures But those hopes were dashed in May this year, after a provisional analysis of the data from the study The study was conducted in newly diagnosed GBM patients with positive EGFR expression and evaluated the efficacy and safety of depatux-m combined with placebo as a standard treatment The results showed that depatux-m did not show any benefit or efficacy signal for patients' survival, and the independent data monitoring committee recommended abandoning the clinical development of the drug This is also the second phase III trial that depatux-m failed in GBM Two years ago, depatux-m combined with temozolomide in the second-line treatment of recurrent GBM patients also failed in the phase III interlince-2 trial Depatux-m was previously tested in gliosarcomas, non-small cell lung cancer, and other solid tumors, but it no longer appears in the pipeline of Aberdeen Abbvie invented the drug, but used technology licensed by Seattle genetics and life sciences pharmaceuticals Because GBM is a difficult problem to overcome, the expectation of depatux-m has not been very high, which is different from the other ADC drug rova-t with the expectation of billions of dollars Unfortunately, the latter is also included in the top 15 list in 2019 Elenbcestat, a bace inhibitor, is the last ad drug in this category, but it was finally announced in September this year that the project was terminated, thus ending the chapter of developing bace inhibitor to treat ad Other bace inhibitors have been shelved due to safety and efficacy issues, and some trials have shown that these drugs have no cognitive impact and in some cases may actually cause symptoms to worsen more quickly Elenbcestat was abandoned after "adverse risk-benefit ratio" was found in the mid-term review of phase III mission ad test data, so safety seems to be the main problem again The first failure in this category was non selective bace inhibitors, which prompted Weicai, Bojian, Novartis and other companies to study whether the drugs selectively blocking BACE1 were more effective, and the results were in vain Novartis's project, umibecestat, a BACE1 inhibitor, was also withdrawn this year Before AstraZeneca and Lilly made the decision to give up the BACE1 inhibitor lanabecestat, the researchers suggested that it might be valuable to use a low-dose bace inhibitor as early as possible in pre symptom AD patients (possibly administered after inhibition with amyloid targeted antibody) Other researchers speculated that a worse outcome in some bace studies might mean that high levels of inhibition of BACE and amyloid peptide may interfere with the normal function of neurons to some extent Now, however, with no bace inhibitors in late clinical trials, these assumptions seem unlikely to be tested, at least in large-scale trials In addition to elenbcestat, only one ad drug (ban2401) was tested in phase III by Bojian and Weicai However, after careful analysis of the extended follow-up data, the unexpected revival of aducanumab means that the antibody is still an active ad project, but its success is not guaranteed, so the antibody is also listed in the top 15 list in 2019 In recent years, Nash has been the focus of the pharmaceutical industry, dozens of treatment methods are in the pipeline, but it has proved to be a difficult problem Eratasan, conatus's Pan caspase inhibitor, is one of the two Nash drugs on the top 15 list in 2019 The failure of the drug made the company lose its partnership with Novartis and forced it to cut 40% of its staff In 2016, Novartis and conatus signed a US $50 million advance payment cooperation agreement to jointly develop emricasan In June of this year, in the phase IIb ENCORE-LF trial in patients with decompensated NASH cirrhosis, there was no significant improvement in event free survival in the emricasan group compared with the placebo group Another study, encore-ph, found that ericasan was not superior to placebo in improving the mean hepatic venous pressure gradient in patients with compensatory Nash cirrhosis This result is based on the mediocre data from many other clinical studies in ericasan, so it's not surprising, but its impact on conatus is far-reaching Conatus also suspended the research and development of cts-2090, a pre clinical Caspase-1 inhibitor, and hired Oppenheimer to study strategic options, trying to find ways to bring some value to investors in trouble At the end of this year, conatus is expected to have only $10 million to $15 million in cash or current assets, so there is little time left for the company Entresto was approved by FDA in July 2015 to treat patients with heart failure (hfref) with reduced ejection fraction, reducing the risk of cardiovascular death and hospitalization for heart failure In 2018, for the first time, the drug's sales exceeded the $1 billion mark Hfref refers to the traditional concept of "systolic" heart failure, which can be seen in patients whose myocardium cannot effectively push oxygen rich blood to the whole body However, heart failure heart failure patients will be discharged from the normal amount of blood, this type of heart failure is known as HFpEF, the traditional concept of "diastolic heart failure", its incidence rate is on the rise Entresto may be effective in HFPEF, which accounts for about half of all cases of heart failure, is more common in women and the elderly, and there is no approved treatment It is estimated that the success of HFPEF may open up a global patient pool of about 13 million people for entresto, who tend to have higher hospitalization rates, lower quality of life and higher risk of death The global phase III paragon-hf trial of entresto in the treatment of HFPEF patients, published in July this year, was disappointing, missed the composite primary end point of reducing cardiovascular death and overall heart failure hospitalization, and threatened Novartis' hope of peak sales of the drug of $5 billion Novartis did not give up expanding the use of entresto The company reported the additional analysis of the paragon-hf study and the results from the paradim-hf study at the American Heart Association Conference in November, indicating that entresto showed "profound impact" in some patients, including women, patients with structural changes in the left ventricle, and patients with lower ejection fraction range Novartis said it would submit new data to global regulators to determine the next step in developing entresto to treat HFPEF Fevipiprant is the second drug that Novartis was listed on the top 15 list in 2019, an oral prostaglandin DP2 receptor antagonist that failed to improve lung function in two phase III trials involving patients with allergic asthma Fevipiprant has been regarded as a potential drug candidate in Novartis pipeline Early trials have shown that the drug may improve the symptoms and lung function of allergic asthma, inhibit inflammation, and even help reverse airway changes Despite hope, fevipiprant failed to improve lung function as measured by FEV1 compared to placebo, both of which involved patients with uncontrolled asthma A phase IIB trial has shown that the drug is the first to reduce the quality of airway smooth muscle and may reduce the use of high-dose steroids in patients Previously, the DP2 antagonists of AstraZeneca, actelion and Amgen also failed in clinical trials Novartis also recognized some characteristics of fevipiprant in early studies, including the lack of dose response Jefferies analysts say the odds of success are only 30% At present, Novartis is still carrying out two clinical trials on fevipiprant in the treatment of moderate and severe asthma deterioration, and the data will be released next year, so the project is not over However, the failure of allergic asthma test has brought pressure to gossamer bio, whose DP2 antagonist GB001 is in phase IIB of eosinophil asthma test, and data is expected to be published next year The biggest disappointment in 2019 in trying to find a new way to treat GBM came from the failure of immunooncology In September, data from the phase III checkmate-548 trial showed that,
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