Amycinpyrifya-sensitive lipid regime agent Phase III clinical lysa-critical.

Today, Celsion announced that its ThermoDox Phase III Clinical Independent Data Monitoring Board (DMC) has recommended the termination of the trial, called OPTIMAsecond mid-term analysis showed that the test had exceeded the previously set invalid threshold (0.900, actual value 0.903), but because of the p-value there was some uncertainty, the DMC left the decision to CLSNthe trial recruited 554 patients with 3-7 cm primary liver cancer, comparing the effects of ThermoDox with radiofrequency pyroelectricalate (RFA) and using RFA alone on OS, pfS as the secondary endpointCLSN plunged 64% todaydrug source analysis seven years ago CLSN because of its partnership with Haizheng made the small company famous in the Chinese pharmaceutical industry, when a phase three clinical failure called HEAT caused Hai to lose $5 million in a short period of time down paymentthe subsequent CLSN's sub-group analysis of the HEAT trial found that a population (medium-sized tumors, single lesions, 45-minute RFA treatment) seemed to be sensitive to ThermoDox, reducing the risk of death by up to 50%, and began a phase III clinical, OPTIMA, for this populationbut this subgroup analysis is very unreliable, as sugar cane to be frosted, radon to be originally, it seems to be related, but coincidentallyof course, clinical observations have concluded that the conclusions are not always unreliable, and many new drugs are also starting with clinical occasional observations, such as the recently listed Dravet drug Finteplais more likely to be false lying based on this subgroup analysis than the therapeutic hypothesis supported by systematic datathe technique itself is slightly higher than body temperature based on the phase change temperature of certain lipids, so the system is slower to release at 37 degreesBut if you raise the temperature in the lesions tissue, you will selectively release the drug in the lesions, the same idea as photosensitive ADCs or even ADCs themselvesRFA is a physical technique for treating liver cancer, using electrodes to raise temperatures locally in the lesionspatients' livers will be heated anyway, and the burden of a heat-sensitive preparation is small, so the choice of this indication is very ingeniousother lipids may have accumulated in tumor tissue through the EPR effect, and the liver is an ideal place for these nano-preparationsis said to increase the EPR effect after heating, and cell drinking is more effectiveCLSN claims the drug is 25 times more abundant in the liver, but an article says the technique in pig models allows amycin to accumulate three times as much in the liver as peripheral tissuesthree times doesn't sound high, but these traditional chemotherapy treatment windows are usually small, if not 1 or less the effective dose of the Dosita preclinical model are accurate to a single digit after the decimal point, so 3 times is a huge increase of course, the accumulation of lesions does not mean that the treatment window is expanded is that even liver cancer patients are still dominated by normal cells, so there are local toxicity problems the second is that killing in situ cancer cells does not necessarily translate into survival advantages, even if radiotherapy is sometimes the effect of systemic effects Another factor is liver cancer itself, which is a difficult-to-treat tumor especially first-line therapies have not progressed for many years, and this year The first-line therapy has been a multikinase inhibitor sorafinini, although this year's Tecentriq/Bevalsatoa is on the market for more than a decade, although this is a high-risk solid tumor about 50% of liver cancer in is caused by chronic hepatitis B, so the cure of hepatitis B can indirectly reduce the death toll from liver cancer rnAi drugs now targeting the main antigen mRNA of hepatitis B showed more than 10% anti-yang rate in early clinical lying, and a non-specific nucleic acid therapy is said to produce 50% transcurrent rate in phase II clinically, but the mechanism is more vague another major cause of liver cancer is NASH, an area that has failed many times in recent years but has several mechanisms that show good prospects such as GLP, FGF21, and thyroid receptor agonists NASH and hepatitis B is not good to treat, but than the late liver cancer may still be easy, so around Wei to save Zhao, cure these two diseases is a reliable strategy .