Less than one year af­ter Alex­ion part­ed with $25 mil­lion up­front to se­cure ac­cess to a sec­ond an­ti-FcRn as­set, it is aban­don­ing the ex­per­i­men­tal drug. The dis­con­tin­u­a­tion, dis­closed at the SVB Leerink Glob­al Health­care Con­fer­ence in New York dur­ing a fire­side chat, bodes well for ri­val Im­muno­vant.

The drug (ABY-039), part­nered for de­vel­op­ment with Swe­den’s Af­fi­body, was for­sak­en on the ba­sis of ear­ly-stage da­ta that was not viewed fa­vor­ably, Baird and SVB Leerink an­a­lysts not­ed.

“We be­lieve that this find­ing could have been due to a neg­a­tive safe­ty sig­nal, as Alex­ion al­so ac­knowl­edged that they knew the pro­gram was high-risk, due to the fact that pri­or bac­te­r­i­al se­quences had sug­gest­ed an in­creased like­li­hood of im­muno­genic­i­ty,” Baird’s Bri­an Sko­r­ney said.

“Giv­en this con­text, we do not be­lieve this dis­con­tin­u­a­tion should raise ques­tions re­gard­ing the po­ten­tial ben­e­fits and mech­a­nis­tic prop­er­ties in­volved with FcRn in­hi­bi­tion since Alex­ion di­a­logue may in­fer the de­ci­sion was safe­ty-based.”

Im­muno­vant’s ri­val drug, IMVT-1401, is in mul­ti­ple on­go­ing Phase II tri­als. SVB Leerink’s Thomas Smith has mod­eled peak sales of ~$2.7 bil­lion for the com­pa­ny’s three iden­ti­fied lead in­di­ca­tions: myas­the­nia gravis, thy­roid eye dis­ease and warm au­toim­mune he­molyt­ic ane­mia.

“(T)he dis­con­tin­u­a­tion of ABY-039 reads through as an in­cre­men­tal pos­i­tive for Im­muno­vant. Mov­ing for­ward, we con­tin­ue to be­lieve that IMVT-1401 pos­sess­es best-in-class po­ten­tial as a rapid­ly ad­min­is­tered and high­ly ef­fi­ca­cious FcRn in­hibitor,” Sko­r­ney said.

With the dis­con­tin­u­a­tion of ABY-039, there is one less FcRn an­ti­body in clin­i­cal de­vel­op­ment. How­ev­er, Alex­ion has an­oth­er an­ti-FcRn as­set it will hold on to — ALXN1830 — which it scored in a 2018 buy­out deal of Syn­tim­mune ($400 mil­lion up­front, with a po­ten­tial $800 mil­lion in mile­stones). There are al­so oth­er com­pa­nies in the space, in­clud­ing ar­genx, Har­bour Bio­Med and Mo­men­ta.

The neona­tal Fc re­cep­tor (FcRn) is an im­munoglob­u­lin G (IgG) and al­bu­min bind­ing pro­tein ex­pressed on the cell sur­face of most hematopoi­et­ic, en­dothe­lial, and ep­ithe­lial cells.

FcRn re­cy­cles IgG an­ti­bod­ies by shut­tling them away from lyso­so­mal degra­da­tion, there­by pre­serv­ing path­o­gen­ic an­ti­body lev­els in IgG-me­di­at­ed dis­eases such as myas­the­nia gravis (a long-term neu­ro­mus­cu­lar con­di­tion). Drugs de­signed to in­hib­it FcRn, there­fore, are de­signed to de­crease to­tal IgG — cru­cial­ly path­o­gen­ic IgG — to treat pa­tients.

So­cial im­age: Alex­ion

With just days before President Joe Biden’s Covid-19 booster rollout is set to go into effect, an FDA advisory committee appeared on the verge of not recommending boosters for anyone in the US before a last-minute change of wording laid the groundwork for older adults to have access to a third dose.

The FDA’s adcomm on Vaccines and Related Biological Products (VRBPAC) roundly rejected Pfizer/BioNTech booster shots for all individuals older than 16 by a 16-2 vote Friday afternoon. Soon after, however, the agency posed committee members a new question limiting booster use to the 65-and-older population and individuals at high risk of disease due to occupational exposure or comorbidities.

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

In recent months, the battle for PD-(L)1 dominance has spilled over into early cancer with Merck’s Keytruda and Bristol Myers Squibb’s Opdivo all alone on the front lines. Keytruda now has another shell in its bandolier, and it could spell a quick approval.

Keytruda cut the risk of relapse or death by 35% over placebo (p=0.00658) in high-risk, stage 2 melanoma patients who had previously undergone surgery to remove their tumors, according to full data from the Phase III KEYNOTE-716 presented Saturday at #ESMO21.

Merck has worked hard to bring its I/O blockbuster Keytruda into earlier and earlier lines of therapy, and now the wonder drug appears poised to make a quick entry into early advanced cervical cancer.

A combination of Keytruda and chemotherapy with or without Roche’s Avastin cut the risk of death by 33% over chemo with or without Avastin (p=<0.001) in first-line patients with persistent, recurrent or metastatic cervical cancer, according to full data from the Phase III KEYNOTE-826 study presented Saturday at #ESMO21.

Facing the big dogs in the PD-(L)1 space, AstraZeneca has taken its own contender Imfinzi into blockbuster territory in its four years on the market but sees even bigger things for the drug. Combinations could be the key, and early results from a mid-stage test are adding some fuel to that strategy.

Imfinzi combined with one of two investigational immunotherapies — a CD73 antibody dubbed oleclumab or an Innate’s anti-NGK2a named monalizumab — topped Imfinzi alone in terms of overall response and progression-free survival in patients with stage III non-small cell lung cancer whose tumors had not worsened during concurrent chemoradiation, according to interim data from the Phase II COAST trial set to be presented at #ESMO21.