On Wednes­day, Rel­ma­da Ther­a­peu­tics ran in­to yet an­oth­er ma­jor prob­lem for its lead can­di­date, two months af­ter fac­ing an ear­li­er set­back.

The CNS-fo­cused biotech re­vealed that REL-1017, its lead can­di­date that it has been de­vel­op­ing for ma­jor de­pres­sive dis­or­der, failed to reach the pri­ma­ry end­point in a Phase III study, look­ing at the drug as an ad­junc­tive treat­ment. The end­point was a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in de­pres­sion symp­toms com­pared to place­bo at 28 days, mea­sured by the Mont­gomery-As­berg De­pres­sion Rat­ing Scale.

In the study, the 113 pa­tients in the REL-1017 treat­ment arm saw a re­duc­tion of 15.1 points on the de­pres­sion scale af­ter 28 days, com­pared to 12.9 days for the 114 pa­tients on place­bo.

In­vestors took is­sue with Rel­ma­da $RLMD, send­ing the biotech’s shares spi­ral­ing more than 50% to un­der $2 a share as the mar­ket opened Thurs­day morn­ing. Its stock price has fall­en more than 90% since Sep­tem­ber, wip­ing away hun­dreds of mil­lions of dol­lars in mar­ket share af­ter REL-1017 failed to meet the pri­ma­ry end­point in a Phase III MDD tri­al as a monother­a­py.

That tri­al showed that af­ter 28 days, pa­tients who took the drug saw their scores de­crease by 14.8 points com­pared to 13.9 points from those on place­bo. Rel­ma­da re­port­ed a p-val­ue of p=0.28 at 28 days.

The biotech point­ed the fin­ger again at the same fac­tors that it blamed for a pre­vi­ous tri­al fail­ure, in­clud­ing “a lim­it­ed num­ber of high en­rolling sites with un­plau­si­ble place­bo re­sponse.” Per a state­ment, “im­plau­si­ble re­sults were again ob­served in two of the same high en­rolling RE­LIANCE I (Study 301) study cen­ters, where place­bo dra­mat­i­cal­ly out­per­formed REL-1017.”

Ex­ecs told in­vestors and an­a­lysts on a con­fer­ence call Wednes­day dis­cussing the re­sults that the com­pa­ny will have dis­cus­sions with FDA, in­clud­ing whether a Phase II tri­al, which did show some pos­i­tive ef­fi­ca­cy da­ta, could be con­sid­ered suf­fi­cient as a suc­cess­ful study.

Rel­ma­da’s goal has been to cre­ate a de­pres­sion drug that acts rapid­ly, in con­trast to SS­RIs that could take weeks to start work­ing. The FDA had ap­proved a rapid-act­ing ther­a­py for MDD back in Au­gust, Ax­some’s Au­veli­ty, which is an NM­DA re­cep­tor an­tag­o­nist. REL-1017 is a ND­MA re­cep­tor “chan­nel block­er,” Rel­ma­da says.

Rel­ma­da said that it will con­tin­ue to en­roll pa­tients in RE­LIANCE II, an­oth­er on­go­ing Phase III tri­al look­ing at REL-1017 as a po­ten­tial ad­junc­tive treat­ment for MDD. How­ev­er, it did say that Rel­ma­da will be im­ple­ment­ing some undis­closed pro­to­col and op­er­a­tional changes to the tri­al, and ad­di­tion­al­ly mak­ing “cer­tain im­prove­ments” to how the tri­al is run.

RE­LIANCE II is the biotech’s last Phase III tri­al look­ing at REL-1017 in MDD.

Rel­ma­da de­clined to com­ment to End­points News out­side of a state­ment and the ear­li­er con­fer­ence call.

The FDA’s Oncology Center of Excellence has been a bright spot within the agency in terms of speeding new treatments to patients. That flexibility was on full display this morning as FDA released new draft guidance spelling out exactly how oncology drug developers can fulfill both the accelerated and full approval’s requirements with just a single randomized controlled trial.

While Congress recently passed legislation that will allow FDA to require confirmatory trials to be recruiting and ongoing prior to granting an accelerated approval, the agency is now making clear that the initial trial used to win the AA, if designed appropriately, can also serve as the trial for converting the accelerated approval into a full approval.

US regulators cleared an ultra-rare drug from Pharming Group, by way of Novartis, on Friday afternoon.

The Dutch biotech said the FDA greenlit leniolisib for an immunodeficiency disease known as activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome, or APDS. People 12 years and older can receive the oral drug, to be marketed as Joenja, beginning early next month, Pharming said, five days ahead of the decision deadline set by the FDA as part of a priority review.

Digital therapeutics company Better Therapeutics announced on Thursday that it’s cutting 35% of its staff as it awaits FDA clearance for its first product.

The company, which launched eight years ago, is one of a growing group of companies seeking a digital alternative to traditional medicine. The space saw a record $7.5 billion in investments in 2021, according to Chris Dokomajilar at DealForma, with uses spanning ADHD, PTSD and other indications. However, private insurers have been slow to hop on board.