Herriot Tabuteau, Axsome CEO (Photo by Owen Hoffmann/Patrick McMullan via Getty Images)

Ax­some's ap­proved de­pres­sion drug clears Alzheimer's ag­i­ta­tion tri­al months af­ter Lund­beck-Ot­su­ka duo

Af­ter an Au­gust ap­proval for treat­ing ma­jor de­pres­sive dis­or­der, Ax­some Ther­a­peu­tics’ tablet for­mu­la­tion of a cough sup­pres­sant and an­ti­de­pres­sant has now cleared a Phase III in an­oth­er in­di­ca­tion.

The drug, known in MDD as Au­veli­ty and un­der the in­ves­ti­ga­tion­al name AXS-05, was bet­ter than place­bo at de­lay­ing the time for ag­i­ta­tion re­lapse in pa­tients with Alzheimer’s, the New York biotech said Mon­day morn­ing. Topline da­ta from the Phase III showed AXS-05 was sta­tis­ti­cal­ly sig­nif­i­cant in de­lay­ing the time to re­lapse, with a p-val­ue of 0.014.

Ax­some claims that’s a 3.6-fold low­er risk of re­lapse as com­pared to place­bo. The so-called AC­CORD tri­al treat­ed 178 pa­tients with the in­di­ca­tion, which has no ap­proved treat­ments. The pri­ma­ry end­point was cal­cu­lat­ed based on the 108 pa­tients who achieved a “sus­tained clin­i­cal re­sponse af­ter open-la­bel treat­ment” and were then ran­dom­ized 1:1 to con­tin­ue with the drug or switch to place­bo.

The num­ber of pa­tients was low­er than ini­tial­ly ex­pect­ed, with 260 orig­i­nal­ly ex­pect­ed to en­roll in the tri­al, Cowen an­a­lysts not­ed.

It could be years be­fore Ax­some is at the FDA’s doorstep with an ap­proval re­quest, though, as the com­pa­ny start­ed a sec­ond AD­VANCE tri­al in Sep­tem­ber. That study won’t read out un­til 2025, the biotech guid­ed dur­ing a quar­ter­ly up­date ear­li­er this month. For now, CEO Her­riot Tabuteau said Ax­some looks to con­fab with the FDA about fu­ture clin­i­cal de­vel­op­ment plans for the in­di­ca­tion.

Joseph Thome

“Giv­en the strong­ly pos­i­tive re­sults of AC­CORD, we look for­ward to the feed­back from the FDA on whether AD­VANCE and AC­CORD could con­sti­tute a reg­u­la­to­ry pack­age, with AD­VANCE-2 serv­ing as more of a con­fir­ma­to­ry tri­al,” Cowen an­a­lyst Joseph Thome wrote in a note short­ly af­ter the da­ta drop. “This sce­nario would be up­side to our late 2025 launch es­ti­mate.”

The da­ta come months af­ter Lund­beck and part­ner Ot­su­ka re­port­ed their own Phase III suc­cess in the in­di­ca­tion, with their de­pres­sion and schiz­o­phre­nia drug Rex­ul­ti. Mean­while, days ear­li­er, Aca­dia’s Alzheimer’s-re­lat­ed psy­chosis drug was giv­en a thumbs-down by FDA’s ad­vi­sors.

In Ax­some’s study, re­lapse pre­ven­tion was al­so ob­served. The rates of re­lapse in the dou­ble-blind por­tion were 7.5% for AXS-05-treat­ed pa­tients and 25.9% for those in the place­bo arm, which equates to a p-val­ue of 0.018, Ax­some said.

The drug de­vel­op­er said ag­i­ta­tion symp­toms were ham­pered start­ing at week 1 on open-la­bel treat­ment and through “all time­points,” as ob­served by the Co­hen-Mans­field Ag­i­ta­tion In­ven­to­ry, or CMAI.

Study in­ves­ti­ga­tors al­so looked at the dis­tress and bur­den on care­givers of the pa­tients dur­ing the open-la­bel por­tion. Those were both sta­tis­ti­cal­ly sig­nif­i­cant com­pared to base­line at weeks 4 and 8, the biotech re­port­ed.

No dis­con­tin­u­a­tions due to ad­verse events were re­port­ed for the AXS-05 group in the dou­ble-blind pe­ri­od, as com­pared to 1.9% for the place­bo co­hort. Ad­verse events were re­port­ed in 28.3% of drug-treat­ed pa­tients and 22.2% in the place­bo arm. A se­ri­ous ad­verse event, a fe­cal im­paction, in the AXS-05 group was de­ter­mined “to be not re­lat­ed to study med­ica­tion,” per an in­ves­ti­ga­tor.

Two and a half years ago, the FDA tagged the drug with break­through ther­a­py des­ig­na­tion for Alzheimer’s dis­ease ag­i­ta­tion. Now, the com­pa­ny is plan­ning to dis­cuss the new da­ta with the FDA “in the con­text of the on­go­ing clin­i­cal de­vel­op­ment of AXS-05 in this in­di­ca­tion,” Tabuteau said in a state­ment.

The break­through ban­ner was grant­ed af­ter a Phase II/III AD­VANCE-1 study showed CMAI to­tal score de­creased by 15.4 points on av­er­age from base­line at week 5. In the AC­CORD study da­ta re­leased Mon­day, CMAI mean re­duc­tions were 6.7 points at week 1, 11.0 points at week 2 and 20.6 points at week 5, which all come out to a p-val­ue be­low 0.001, Ax­some said.

Ax­some is al­so test­ing the drug in a mid-stage study for smok­ing ces­sa­tion.

The Big Phar­ma dis­card pile; Lay­offs all around while some biotechs bid farewell; New Roche CEO as­sem­bles top team; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

With earnings seasons in full swing, we’ve listened in on all the calls so you don’t have to. But news is popping up from all corners, so make sure you check out our other updates, too.

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Raymond Stevens, Structure Therapeutics CEO

Be­hind Fri­day's $161M IPO: A star sci­en­tist, GPCR drug dis­cov­ery and a plan to chal­lenge phar­ma in di­a­betes

What does it take to pull off a $161 million biotech IPO these days?

In Structure Therapeutics’ case, it means having a star scientist co-founder paired with the computational drug discovery company Schrödinger, $198 million in private funding from blue-chip investors, almost six years of research work on G protein-coupled receptors and a slate of oral, small-molecule drugs, with an eye on the huge and growing diabetes and weight-loss market.

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Ma­gen­ta halts stem cell work and may sell it­self fol­low­ing pa­tient death, clin­i­cal hold

Magenta Therapeutics said it is halting work on its stem cell transplant drug pipeline and may sell itself, a week after the company reported the death of a patient in an early stage trial of its antibody-drug conjugate.

The Cambridge, MA-based company said it will conduct a “review of strategic alternatives,” and that could include an “acquisition, merger, business combination, or other transaction.”

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Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

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Trodelvy notch­es a win in most com­mon form of breast can­cer

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

Sanofi scraps PhI­II tri­al for Prin­cip­ia drug af­ter re­view­ing com­pe­ti­tion

Months after the FDA placed Phase III trials of Sanofi’s BTK inhibitor on hold, the company is winding down one of the studies.

Sanofi reported in its Q4 earnings that the URSA study “was discontinued after careful evaluation of the emerging competitive treatment landscape in” myasthenia gravis, a rare disease that causes muscle weakness.

The Phase III, placebo-controlled trial was testing tolebrutinib in patients with the moderate-to-severe form of the disease. It started in late 2021, according to records on clinicaltrials.gov, and was originally designed to recruit 154 participants who were receiving the standard of care.

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Af­ter 13 years, Ramy Mah­moud steps in­to CEO seat at Opti­nose; Ru­pert Vessey set to ex­it Bris­tol My­ers in Ju­ly

After 13 years as president and COO at Optinose, Ramy Mahmoud has stepped into a new role as its CEO. He is taking the place of Peter Miller, who stepped down earlier this week, though Miller is still staying with the company as a consultant.

In 2010, the two business partners joined Optinose to take it in a new direction, transforming it from a delivery platform to product company. They previously worked together at Johnson & Johnson, when Miller was president at Janssen and Mahmoud headed medical affairs. Miller said after he learned about Optinose, “I did what I always do, which is find people smarter than me to talk with about the idea. And the first person I called was Ramy … and I said, ‘Hey, Ramy, what do you think of this technology?’”

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How to use ex­ter­nal con­trols: FDA spells out think­ing in new draft guid­ance

The use of real-world evidence to inform the FDA’s decision-making continues apace, with the agency releasing new draft guidance yesterday on how sponsors can compare outcomes of trial participants receiving a test treatment with outcomes in a group of people external to the trial.

The practice of externally controlled trials is common, particularly in oncology or other difficult areas where it’s not ethical or feasible to use internal controls.

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The Big Phar­ma axe: Mer­ck cuts chikun­gun­ya vax, Bris­tol My­ers drops Cy­tomX-part­nered pro­gram, and more

As fourth quarter earnings come in, Big Pharmas are disclosing changes to their pipelines during their investor calls, and sometimes more quietly in presentation appendices.

Merck dropped its chikungunya vaccine candidate, which completed a Phase II study. Merck acquired the vaccine through its purchase of Themis Bioscience in 2020. In developing a vaccine for chikungunya, a mosquito-borne virus, Valneva is the frontrunner, as it submitted its vaccine to the FDA at the end of December.

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