Shares of Ax­some Ther­a­peu­tics $AXSM shot up Mon­day morn­ing on the sur­prise news that its lead drug scored sta­tis­ti­cal­ly sig­nif­i­cant re­sults for Alzheimer’s ag­i­ta­tion, a rel­a­tive­ly green field in drug R&D, in what’s billed as a piv­otal Phase II/III tri­al. But the com­pa­ny will have plen­ty of high-risk work to do be­fore it can ex­pect an FDA ap­proval.

Com­ing off the ropes of a late-stage fail for AXS-05 in treat­ment-re­sis­tant de­pres­sion, the biotech re­ports that their drug scored well against a place­bo based on a care­giv­er-rat­ed scale of Alzheimer’s pa­tients’ be­hav­ior, which in­cludes track­ing episodes of scream­ing or hit­ting. At week 5 re­searchers tracked mean re­duc­tions from base­line of 15.4 points for AXS-05 and 11.5 points for place­bo, giv­ing them a p val­ue of 0.010.

The drug, a com­bi­na­tion of 2 ther­a­pies — dex­tromethor­phan and bupro­pi­on — al­so beat out bupro­pi­on alone. And the drug achieved su­pe­ri­or­i­ty at week 3, ac­cord­ing to the com­pa­ny.

An­a­lysts, mean­while, have been pri­mar­i­ly track­ing this drug’s po­ten­tial in ma­jor de­pres­sive dis­or­der, where the com­pa­ny is lin­ing up a near-term ap­pli­ca­tion with the FDA af­ter re­port­ing up­beat da­ta in one of the tough­est fields in R&D. That left ex­pec­ta­tions low as the biotech ac­cel­er­at­ed the study read­out due to Covid-19 in­to Q2 from Q3.

Marc Good­man at SVB Leerink re­cent­ly not­ed:

In fact, we don’t be­lieve in­vestors in­clude any­thing for this in­di­ca­tion, and with good da­ta, we would as­sume the stock could be up $18 if in­vestors as­sume $650M of added peak sales at 50% POS, which we think is very rea­son­able.

Ac­tu­al­ly, the ini­tial re­sponse was much bet­ter than that, as Ax­some stock gy­rat­ed up more than 40% on the news. This is an un­cer­tain are­na, though, with re­searchers of­ten forced to stick with dif­fi­cult end­points and tough place­bo re­spons­es as care­givers track re­spons­es.

Good­man and oth­ers like to point out that no oth­er drug has been specif­i­cal­ly ap­proved for Alzheimer’s ag­i­ta­tion, leav­ing this a big op­por­tu­ni­ty. But oth­ers have tried and failed to make the da­ta stick, and this is an area where reg­u­la­tors will like­ly de­mand plen­ty of pos­i­tive da­ta.

Ot­su­ka’s Avanir un­der­scored just how dif­fi­cult this could be with their pro­gram for AVP-786 — deudex­tromethor­phan hy­dro­bro­mide [d6-DM]/quini­dine sul­fate) — which first scored a win in the first Phase III and then flopped in the sec­ond last fall.

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

The Drugs for Neglected Diseases initiative (DNDi) and Sanofi today said that their potential sleeping sickness treatment saw success rates of up to 95% from a Phase II/III study investigating the safety and efficacy of single-dose acoziborole.

The potentially transformative treatment for sleeping sickness would mainly be targeted at African countries, according to data published today in The Lancet Infectious Diseases medical journal. The clinical trial was led by DNDi and its partners in the Democratic Republic of the Congo (DRC) and Guinea, with the authors noting: