Hopes (and Stock Valuations) Tumble As New Herpesvirus Drug Tanks
Brincidofovir, better known to many in the chronic fatigue syndrome (ME/CFS) community as CMX001 tanked in its large Phase III trial. To say such a result was unexpected would be understating things. A lipid forumulated version of Vistide, Brincidofovir, demolished other anti-herpesvirus drugs in laboratory studies. They suggested that Brincidofovir should not only be considerably more powerful than other antivirals but that should cause many fewer side effects.
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[/fright]ME/CFS patients and doctors hoped the days of very long duration, expensive, high dose antiviral regimens to treat simmering herpesvirus infections might be over. With the company expressing interest in ME/CFS patients with documented herpesvirus infections some hoped an ME/CFS/herpesvirus trial might be next.
It's not to be so - at least not yet. The drug managed to meet one important endpoint: it did dramatically reduce the frequency of cytomegalovirus infections in transplant patients when they were on the drug.
Shortly after the transplant patients went off the drug, though, their rates of CMV infections soared. By the end of the trial no difference in CMV infections was found between the brincidofovir treated patients and the controls. When that result was announced Chimerix's stock price dropped eighty percent.
Did Doctors Unknowingly Sabotage the Trial?
All may not be lost. Chimerix researchers found that the increased infections occurred in patients treated with steroids for diarrhea. Suspecting the diarrhea was caused by a potentially fatal outcome called graft versus host disease (GHVD), the doctors hit the patients with immune suppressing steroids which resulted in increased rates of infection.
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[/fright]Diarrhea, however, is also a known side effect of brincidofovir which can be managed by pausing the dose. Chimerix officials belief the doctors in the study mistook a side effect of brincidofovir for GHVD. The fact that eight times as many corticosteroids were given in the Brincidofovir arm as in the control arm suggested Chimerix was right. Chimerix noted that patients given a temporary pause in treatment - as suggested in the treatment guidelines - did not end up with higher frequencies of CMV infection.
Ultimately some doctors inability to follow the study protocols not only may have ruined an enormously expensive study (450 transplant patients) and prevented a good drug from getting to the market but may have also killed some of the patients in the study. Oddly, brincidofovir, may have doubly improved its worth as it was able to keep CMV under control even as some patients were bring given immune suppressing drugs. Once brincidofovir was discontinued, however, the CMV infections - some of which were fatal - showed up in spades.
Back to the Drawing Board
Hopes for the drug remain high, but Chimerix immediately stopped all Phase III trials and went back to the drawing board with some Phase II trials. The HHV-6 Foundation reported that Chimerix is developing an IV form of the drug which should eliminate problems with diarrhea and more trials are expected this year. Hopefully only time and money has been lost.
The HHV-6 Foundation also noted that the earlier introduction of this drug in the Phase III trial compared to the Phase II trial could have played a role. Other trials suggest that early introduction of antivirals may, in some cases, impair a developing immune response and result in a higher frequency of later infections.
It's also possible that longer drug treatment regimens may be helpful. The Foundation pointed to a valganciclovir trial which found dramatically lower rates of infections in transplant patients receiving the drug for a year vs three months.
The Foundation reported that two other new anti-herpes virus drugs are currently either in Phase I or II clinical trials
Brincidofovir, better known to many in the chronic fatigue syndrome (ME/CFS) community as CMX001 tanked in its large Phase III trial. To say such a result was unexpected would be understating things. A lipid forumulated version of Vistide, Brincidofovir, demolished other anti-herpesvirus drugs in laboratory studies. They suggested that Brincidofovir should not only be considerably more powerful than other antivirals but that should cause many fewer side effects.
[fright]
It's not to be so - at least not yet. The drug managed to meet one important endpoint: it did dramatically reduce the frequency of cytomegalovirus infections in transplant patients when they were on the drug.
Shortly after the transplant patients went off the drug, though, their rates of CMV infections soared. By the end of the trial no difference in CMV infections was found between the brincidofovir treated patients and the controls. When that result was announced Chimerix's stock price dropped eighty percent.
Did Doctors Unknowingly Sabotage the Trial?
All may not be lost. Chimerix researchers found that the increased infections occurred in patients treated with steroids for diarrhea. Suspecting the diarrhea was caused by a potentially fatal outcome called graft versus host disease (GHVD), the doctors hit the patients with immune suppressing steroids which resulted in increased rates of infection.
[fright]
Ultimately some doctors inability to follow the study protocols not only may have ruined an enormously expensive study (450 transplant patients) and prevented a good drug from getting to the market but may have also killed some of the patients in the study. Oddly, brincidofovir, may have doubly improved its worth as it was able to keep CMV under control even as some patients were bring given immune suppressing drugs. Once brincidofovir was discontinued, however, the CMV infections - some of which were fatal - showed up in spades.
Back to the Drawing Board
Hopes for the drug remain high, but Chimerix immediately stopped all Phase III trials and went back to the drawing board with some Phase II trials. The HHV-6 Foundation reported that Chimerix is developing an IV form of the drug which should eliminate problems with diarrhea and more trials are expected this year. Hopefully only time and money has been lost.
The HHV-6 Foundation also noted that the earlier introduction of this drug in the Phase III trial compared to the Phase II trial could have played a role. Other trials suggest that early introduction of antivirals may, in some cases, impair a developing immune response and result in a higher frequency of later infections.
It's also possible that longer drug treatment regimens may be helpful. The Foundation pointed to a valganciclovir trial which found dramatically lower rates of infections in transplant patients receiving the drug for a year vs three months.
The Foundation reported that two other new anti-herpes virus drugs are currently either in Phase I or II clinical trials
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