Near­ly two months af­ter hand­ing Y-mAbs a re­fusal to file let­ter for one of its main neu­rob­las­toma can­di­dates, the FDA gave the biotech an ac­cel­er­at­ed OK for the oth­er — but with a box warn­ing.

Y-mAbs, which flew most­ly un­der the radar un­til a few years ago, snagged ap­proval for naxi­ta­m­ab as a sec­ond-line treat­ment in com­bi­na­tion with gran­u­lo­cyte-macrophage colony-stim­u­lat­ing fac­tor (GM-CSF). Pa­tients old­er than 1 year old can take the drug for re­lapsed or re­frac­to­ry high-risk neu­rob­las­toma in the bone or bone mar­row. The good news cush­ioned last month’s blow, send­ing the com­pa­ny’s stock $YMAB — which sank more than 18% up­on news of the RTF — up 10.15% as of Mon­day morn­ing.

Naxi­ta­m­ab, now mar­ket­ed as Danyelza, was grant­ed pri­or­i­ty re­view in ear­ly June. Theex-Gen­mab ex­ecs run­ning Y-mAbs snagged it from Memo­r­i­al Sloan Ket­ter­ing, along with the biotech’s oth­er neu­rob­las­toma can­di­date, om­bur­tam­ab. The ap­proval rolled in just be­fore Thanks­giv­ing, a few days be­fore the can­di­date’s PDU­FA date.

Un­like om­bur­tam­ab, which tar­gets B7-H3, Danyelza goes af­ter GD2 — a com­mon anti­gen on the cell sur­face of var­i­ous tu­mors. It’s tak­en thrice week­ly, re­peat­ed every four weeks. Ac­cord­ing to the com­pa­ny’s S-1, a mouse ver­sion was used on pres­i­dent and founder Thomas Gad’s daugh­ter, who was di­ag­nosed with high-risk neu­rob­las­toma at age 2. She lat­er re­lapsed and be­gan tak­ing om­bur­tam­ab about 11 years ago, and has been dis­ease-free since.

“It’s very ex­cit­ing to see this treat­ment go from be­ing an ex­per­i­men­tal ther­a­py used at my daugh­ter’s bed­side to now be­ing FDA ap­proved,” Gad said in a state­ment.

The FDA based its de­ci­sion on two piv­otal stud­ies, which showed the drug was well-tol­er­at­ed with “clin­i­cal­ly man­age­able” ad­verse ef­fects, ac­cord­ing to the com­pa­ny. Reg­u­la­tors briefly put the pro­gram on a par­tial clin­i­cal hold back in 2017, due to “pro­posed ac­cep­tance cri­te­ri­on for the AD­CC‑CD16, AD­CC‑CD32, and CDC as­says” which were “too wide to pro­vide suf­fi­cient con­trol over these at­trib­ut­es,” ac­cord­ing to an SEC fil­ing. Y-mAbs sub­mit­ted a com­plete re­sponse to the par­tial hold in May 2018, and it was re­moved the fol­low­ing month.

The ap­proval comes with a box warn­ing, which states that Danyelza has been linked to se­ri­ous in­fu­sion re­ac­tions like ana­phy­lax­is, car­diac ar­rest, bron­chospasm, stri­dor and hy­poten­sion. One case of trans­verse myelitis and two cas­es of pos­te­ri­or re­versible en­cephalopa­thy syn­drome were re­port­ed, ac­cord­ing to the la­bel. Se­vere pain and se­vere hy­per­ten­sion were al­so list­ed as po­ten­tial side ef­fects.

But the most com­mon side ef­fects were most­ly mild and mod­er­ate, ac­cord­ing to the la­bel. They ranged from in­fu­sion-re­lat­ed re­ac­tion to pe­riph­er­al neu­ropa­thy to ede­ma.

“This ap­proval of Y-mAbs’ first BLA rep­re­sents a key step in work­ing to­wards our mis­sion of be­com­ing a world leader in de­vel­op­ing bet­ter and safer an­ti­body-based on­col­o­gy prod­ucts ad­dress­ing un­met pe­di­atric and adult med­ical needs,” CEO Claus Moller said in a state­ment.

Claus Moller

Go­ing forth, the FDA is re­quir­ing a con­fir­ma­to­ry tri­al with a min­i­mum of 80 pa­tients. The study will mea­sure over­all re­sponse rate, with du­ra­tion of re­sponse as the sec­ondary end­point. Pro­gres­sion-free sur­vival and over­all sur­vival are both long-term sec­ondary end­points.

As for om­bur­tam­ab, Y-mAbs ex­pects to meet with the FDA and re­sub­mit its ap­pli­ca­tion by the end of the year. The RTF cit­ed the need for more in­for­ma­tion on man­u­fac­tur­ing and clin­i­cal mod­ules, the com­pa­ny said. While it didn’t spec­i­fy ex­act­ly what reg­u­la­tors are look­ing for, Y-mAbs said it will pro­vide sup­ple­men­tary da­ta from a Phase II study on tu­mor re­sponse from the first 24 pa­tients in the tri­al.

Naxi­ta­m­ab is in sev­er­al oth­er Phase II tri­als, in­clud­ing pe­di­atric front-line high-risk neu­rob­las­toma and re­lapsed sec­ond-line os­teosar­co­ma.

More than five years after Corey Fishman and Michael Dunne dusted sulopenem off Pfizer’s shelves — the second castoff antibiotic they’ve brought out of the pharma giant — and founded Iterum Therapeutics around that single drug, they have lined up a quick shot at approval with priority review from the FDA.

The decision, six months from now, will mark a make-or-break moment for a struggling biotech that has just enough cash to keep the lights on until the third quarter.

Immunocore spent much of 2019 dealing with the fallout of the Neil Woodford scandal, as the former star investor’s fall crashed the biotech’s valuation out of unicorn range. Now it turns out that the company spent 2020 dealing with another internal scandal.

The longtime UK biotech darling disclosed in their IPO filing last week that they had fallen victim to an alleged kickback scheme involving one of their employees. After a whistleblower came forward, they said in their F-1, they spent the summer and spring investigating, finding fraud on the part of an employee and two outside vendors.