Ax­some re­ports late-stage de­pres­sion tri­al de­feat, shares wilt

Months af­ter re­port­ing its ex­per­i­men­tal drug cleared a late-stage study in ma­jor de­pres­sive dis­or­der, Ax­some Ther­a­peu­tics un­veiled da­ta from a piv­otal study in treat­ment-re­sis­tant de­pres­sion that showed the drug failed to meet the main goal.

In gen­er­al, tri­als test­ing de­pres­sion drugs are no­to­ri­ous­ly tricky and prone to fail­ure, in ma­jor part due to high rates of the place­bo ef­fect. Ex­ist­ing an­ti­de­pres­sants of­ten take weeks to kick in, and typ­i­cal­ly work on­ly in some pa­tients. This tri­al test­ed the ther­a­py in pa­tients who had failed to ben­e­fit from two or three pri­or treat­ments.

The pill AXS-05, which con­sists of a com­bi­na­tion of dex­tromethor­phan (DM) and bupro­pi­on, was test­ed against bupro­pi­on alone in TRD pa­tients for 6 weeks in the late-stage 312-pa­tient STRIDE-1 study. Da­ta showed the com­pa­ny’s ther­a­py in­duced a nu­mer­i­cal re­duc­tion on the Mont­gomery-Ås­berg de­pres­sion rat­ing scale, av­er­aged over the 6-week treat­ment pe­ri­od, ver­sus bupro­pi­on (p<0.001), but did not achieve sta­tis­ti­cal sig­nif­i­cance.

At week 6, AXS-05 in­duced a mean re­duc­tion of 11.6 on the rat­ing scale, ver­sus 9.4 on the bupro­pi­on arm (p=0.117).

But the com­pa­ny was en­thu­si­as­tic about the key sec­ondary end­points, which were met. Da­ta showed the Ax­some ther­a­py sig­nif­i­cant­ly im­proved symp­toms over the en­tire six week pe­ri­od with mean re­duc­tions of 8.6 for AXS-05 ver­sus 6.7 for bupro­pi­on (p=0.031). The com­pa­ny’s ex­per­i­men­tal ther­a­py al­so start­ed to show signs of work­ing as ear­ly as week 1, with a re­duc­tion of 5.2 ver­sus 3.6 on the bupro­pi­on arm (p=0.02).

The com­pa­ny now plans to con­duct an­oth­er late-stage study, where it will like­ly test AXS-05 against a place­bo. That study is ex­pect­ed to kick off in the third quar­ter. An ap­pli­ca­tion to mar­ket the ther­a­py in MDD pa­tients is ex­pect­ed to be sub­mit­ted in the sec­ond half of 2020.

The com­pa­ny has not­ed in the past that “a neg­a­tive STRIDE-1 read­out would have no im­pact on the NDA fil­ing in MDD and lim­it­ed im­pact on AXS-05’s com­mer­cial prospects, which al­ready has a dif­fer­en­ti­at­ed pro­file in­clud­ing new MoA, rapid on­set, large ef­fect size and fa­vor­able tol­er­a­bil­i­ty rel­a­tive to cur­rent ther­a­pies,” SVB Leerink an­a­lysts wrote in a note last month.

But in­vestors did not ap­pear to be con­vinced. The New York-based com­pa­ny’s shares $AXSM tum­bled about 18% at $52.12 in pre­mar­ket trad­ing.

AXS-05, which has been grant­ed fast track sta­tus by the FDA, is al­so be­ing test­ed as a treat­ment for ag­i­ta­tion as­so­ci­at­ed with Alzheimer’s and smok­ing ces­sa­tion.

A sep­a­rate ap­pli­ca­tion to mar­ket an­oth­er ex­per­i­men­tal ther­a­py, AXS-07, for use in acute mi­graine is al­so be­ing pre­pared. In De­cem­ber, Ax­some re­port­ed mid-stage da­ta that showed its for­mu­la­tion of an old con­tro­ver­sial Pfiz­er drug was ef­fec­tive in treat­ing nar­colep­sy in a small study.

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Cancer R&D chief José Baselga calls the disease-free survival data for their drug in an adjuvant setting of early stage, epidermal growth factor receptor-mutated NSCLC patients following surgery “momentous.” Roy Herbst, the principal investigator out of Yale, calls it “transformative.”

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Paul Hudson, Sanofi CEO (Getty Images)

Sanofi CEO Paul Hud­son has $23B burn­ing a hole in his pock­et. And here are some hints on how he plans to spend that

Sanofi has reaped $11.1 billion after selling off a big chunk of its Regeneron stock at $515 a share. And now everyone on the M&A side of the business is focused on how CEO Paul Hudson plans to spend it.

After getting stung in France for some awkward politicking — suggesting the US was in the front of the line for Sanofi’s vaccines given American financial support for their work, versus little help from European powers — Hudson now has the much more popular task of managing a major cash cache to pull off something in the order of a big bolt-on. Or two.

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David Chang, Allogene CEO (Jeff Rumans)

Head­ed to PhII: Al­lo­gene CEO David Chang com­pletes a pos­i­tive ear­ly snap­shot of their off-the-shelf CAR-T pi­o­neer

Allogene CEO David Chang has completed the upbeat first portrait of the biotech’s off-the-shelf CAR-T contender ALLO-501 at virtual ASCO today, keeping all eyes on a drug that will now try to go on to replace the first-wave personalized pioneers he helped create.

The overall response rate outlined in Allogene’s abstract for treatment-resistant patients with non-Hodgkin lymphoma slipped a little from the leadup, but if you narrow the patient profile to treatment-naïve patients — removing the 3 who had previous CAR-T therapy who didn’t respond, leaving 16 — the ORR lands at 75% with a 44% complete response rate. And 9 of the 12 responders remained in response at the data cutoff, offering a glimpse on durability that still has a long way to go before it can be completely nailed down.

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The Avance Clinical leadership team: CEO Yvonne Lungershausen, Sandrien Louwaars - Director Business Development Operations, Gabriel Kremmidiotis - Chief Scientific Officer, Ben Edwards - Chief Strategy Officer

How Aus­tralia De­liv­ers Rapid Start-up and 43.5% Re­bate for Ear­ly Phase On­col­o­gy Tri­als

About Avance Clinical

Avance Clinical is an Australian owned Contract Research Organisation that has been providing high-quality clinical research services to the local and international drug development industry for 20 years. They specialise in working with biotech companies to execute Phase 1 and Phase 2 clinical trials to deliver high-quality outcomes fit for global regulatory standards.

As oncology sponsors look internationally to speed-up trials after unprecedented COVID-19 suspensions and delays, Australia, which has led the world in minimizing the pandemic’s impact, stands out as an attractive destination for early phase trials. This in combination with the streamlined regulatory system and the financial benefits including a very favourable exchange rate and the R & D cash rebate makes Australia the perfect location for accelerating biotech clinical programs.

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