Hemophilia gene therapy comes to an end

Biomarin today announced that it will use its phase I / II clinical data and some phase III clinical data of valrox gene therapy for hemophilia A to apply for accelerated approval and listing at the end of this yearAmong the 20 patients in the third phase of clinical practice, 17 factor VIII (F8) can be evaluated, and the median level of F8 in 8 patients at 23-26 weeks is more than 40 IU / dlExperts estimate that the product is expected to become the first type a hemophilia gene therapy to be launched in the middle of next year, with an estimated price of $2-3 millionThe merger of spark, the second ranked company, which was examined by FTC, may have some relationship with the monopoly potential of hemophilia market, and the acquisition will be postponed to next yearSangamo and Pfizer's sb-525 also published some early dataTwo of the four high-dose patients observed the level of F8 over 50 IU / dl for 24 weeksThe other two did not reach this level due to the short observation time (< 10 weeks), but the growth trend was similar to that of the first two patientsUniqure also published early data on gene therapy amt-061 for hemophilia B, with factor IV levels reaching an average of 45% of normal in three patients after 36 weeks of treatment< br / > drug source analysis < br / > hemophilia is a common disease in rare diseases, with a market value of 10-20 billion US dollarsStandard therapy is expensive and inconvenient, and becomes the focus of new therapyRoche's bispecific antibody hemlibra is a major breakthrough, which is also the reason why the acquisition of spark was questioned by FTC, but it is a troublesome thing for some patients to produce neutralizing antibodiesAlthough the hemophilia treatment window is large (some normal people have 150% of F8 without coagulation disorders), the RNAi drug fitusiran has been called off clinical trials due to coagulation eventsNow, several gene therapy companies mentioned above are expected to enter the market within a few years, so bmrn tries to go public ahead of time to get the initiativeSanofi spent 11.6 billion to acquire bivv the year before lastA modified F8 preparation, bivv001 (rfviiifc-vwf-xten), has a half-life that is nearly twice longer than that of rFVIII itself and is more convenient to useIt is a micro innovation< br / > the sb-525 data looked good, which made sgmo stock up 17% and bmrn down 2% at one time today But this is the early data of a very small experiment after all Valrox's F8 level is similar to this level at 24 weeks, but it has declined since 30 weeks Fortunately, the decline slowed down in the next three years and now seems to be stable at about 20% There were 10 patients and 4 doses in sb-525 trial, only the highest dose had significant effect, the other three doses had only slight improvement in F8 level However, there was also a case of severe hypotension and a case of transaminase rise in high dose, although there were not too serious consequences The biggest advantage of valrox is that the observation time of high-dose patients has reached 3 years Although the level of F8 is lower than that of peak period, 20% of normal level is still enough to maintain 0% of annual bleeding rate (ABR), which is very difficult to exceed Another important advantage of bmrn is its production facilities Gene therapy is different from traditional medicine, mass production and distribution is still an important technical obstacle One of the advantages of sb-525 is that it has low immunogenicity and does not need to use steroids to prevent immune response, while Spark's sp8001 uses steroids in early clinical and its efficacy is not as good as the other two products < br / > in addition to the main technical problem of delivery, gene therapy requires a deep understanding of the biological process of interference due to its irreversibility, which also limits the speed of progress in this field Gene therapy has entered the mature stage at least in the field of low hanging fruit, such as ophthalmology and central nervous system, which can be administered locally at low concentration Hemophilia is a disease with a large therapeutic window, and there is a natural mutation F8 with high activity that can be used Hepatocytes can express F8, and the delivery efficiency is not too high, but also can express F8 at a sufficient level, which makes the system have enough window for drug administration Other tissue diseases such as DMD may be more difficult, because a certain proportion of muscle cells need to have a certain proportion of gene therapy in order to have functional improvement Nutritive myoprotein also exceeds the drug loading capacity of AAV, but recently Pfizer and Sarepta's micronutrient myogene therapy have achieved good results However, the window may be very limited, and Sarepta and solid encounter excessive dose of side effects < br / > gene therapy is expected to enter into disease treatment in large quantities According to statistics, there are more than 80 in vivo and in vitro gene therapy in the third phase of clinical research Although this provides a chance to cure many diseases without any treatment, it also puts great pressure on the payment system 10000 SMA patients can afford to use $2 million of drugs, but if dozens of such products enter the market, the payment department will be unable to help, and now there are insurance companies boycotting zolgensma In order to get high price of gene therapy, we should not only have temporary significant effect, but also show long-term stable effect For diseases with standard therapies (such as hemophilia), gene therapy should not only have a difference in efficacy, but also in proportion to the difference in cost Not all products can meet these standards In fact, several of the earliest gene therapies on the market have been basically withdrawn from the market < br / > original title: original hemophilia gene therapy comes to an end, and the battle of F8 is on the verge