Piv­otal myas­the­nia gravis da­ta from ar­genx au­gur well for FcRn in­hibitors in de­vel­op­ment

Lead­ing the pack of biotechs vy­ing for a piece of the gen­er­al­ized myas­the­nia gravis (gMG) mar­ket with an FcRn in­hibitor, ar­genx on Tues­day un­veiled keen­ly an­tic­i­pat­ed pos­i­tive late-stage da­ta on its lead as­set, bring­ing it one step clos­er to reg­u­la­to­ry ap­proval and lift­ing its stock by more than a third.

De­spite steroids, im­muno­sup­pres­sants, acetyl­cholinesterase in­hibitors, and Alex­ion’s Soliris, pa­tients with the rare, chron­ic neu­ro­mus­cu­lar dis­or­der (more than 100,000 in the Unit­ed States and Eu­rope) don’t nec­es­sar­i­ly ben­e­fit from these ex­ist­ing op­tions, leav­ing room for the crop of FcRn in­hibitors in de­vel­op­ment.

Bel­gium-based ar­genx’s ex­per­i­men­tal drug, ef­gar­tigi­mod, was test­ed against a place­bo over 26 weeks in 167 adults with gen­er­al­ized myas­the­nia gravis (gMG) who were on back­ground gMG ther­a­py in the late-stage study chris­tened ADAPT.

In the study, 67.7% of acetyl­choline re­cep­tor-an­ti­body pos­i­tive pa­tients treat­ed with ef­gar­tigi­mod achieved the pri­ma­ry end­point — the per­cent­age of re­spon­ders (a re­spon­der was de­fined as ≥2 point im­prove­ment for at least 4 con­sec­u­tive weeks, dur­ing the first 8-week pe­ri­od) on a dai­ly liv­ing with MG scale — com­pared with 29.7% on place­bo (p<0.0001).

On the sec­ondary goal, 63.1% of those pa­tients re­spond­ed to ef­gar­tigi­mod com­pared with 14.1% on place­bo on an­oth­er scale called Quan­ti­ta­tive Myas­the­nia Gravis (QMG) (p<0.0001). Oth­er sec­ondary end­points, in­clud­ing time on tri­al in clin­i­cal­ly mean­ing­ful im­prove­ment and fast on­set of re­sponse, were al­so found to be sta­tis­ti­cal­ly sig­nif­i­cant, al­though the time to qual­i­fy for re­treat­ment end­point was not met.

“While re­spon­der cri­te­ria in ar­genx’s ADAPT tri­al are slight­ly dif­fer­ent than those uti­lized in the piv­otal tri­als of Alex­ion’s Soliris, we broad­ly view ar­genx’s top-line da­ta as strong in com­par­i­son to the piv­otal da­ta from Soliris, and be­lieve this da­ta could po­si­tion FcRN in­hi­bi­tion as hav­ing a sig­nif­i­cant role …” Baird’s Bri­an Sko­r­ney wrote in a note.

Mean­while, there were no red flags on the safe­ty side. “Over­all, we think the like­ly speed of on­set and def­i­nite­ly the safe­ty of ef­gar­tigi­mod com­pares ex­treme­ly well to stan­dard of care ther­a­pies, such as IVIG and PLEX, which have rapid on­set but are no­to­ri­ous for their safe­ty is­sues,” Stifel an­a­lysts wrote in a note.

Shares of the com­pa­ny $ARGX shot up near­ly 33% to $210 on the Nas­daq in Tues­day morn­ing trad­ing.

With these re­sults, ar­genx plans to sub­mit a mar­ket­ing ap­pli­ca­tion for the IV for­mu­la­tion (60 min in­fu­sion) by the end of 2020. If ap­proved, like­ly by 2021, this ver­sion of the prod­uct should pave the way for the com­pa­ny’s sub­cu­ta­neous for­mu­la­tion (pack­aged as a sin­gle ~5 mL in­jec­tion) to boost com­mer­cial prospects. Stifel an­a­lysts fore­cast ~$1.7 bil­lion in peak sales for both ef­gar­tigi­mod for­mu­la­tions for use in MG pa­tients.

Oth­er play­ers with FcRn in­hibitors in the pipeline for MG in­clude UCB’s rozano­lix­izum­ab (~30 min sub­cu­ta­neous in­fu­sion), Mo­men­ta Phar­ma­ceu­ti­cals’ nipocal­imab (~7.5-15 min IV in­fu­sion, with a sub­cu­ta­neous for­mu­la­tion in de­vel­op­ment), Im­muno­vant’s IMVT-1401 (two sub­cu­ta­neous in­jec­tions of 2 mL each per dose) and Alex­ion’s ALXN1830 (a sub­cu­ta­neous in­fu­sion that will be test­ed in a Phase II tri­al planned for the sec­ond half of 202o). Apart from ef­fi­ca­cy, the con­ve­nience of dos­ing and du­ra­tion will play a key role in the adop­tion of these FcRn ther­a­pies, an­a­lysts said.

Ar­genx’s re­sults fur­ther val­i­date the an­ti-FcRn mech­a­nism in MG and bode well for the mid-stage nipocal­imab read­out ex­pect­ed in the com­ing weeks, Stifel an­a­lysts added on Tues­day.

MG oc­curs when IgG an­ti­bod­ies dis­rupt com­mu­ni­ca­tion be­tween nerves and mus­cles, caus­ing po­ten­tial­ly life-threat­en­ing mus­cle weak­ness. More than 85% of pa­tients progress to gen­er­al­ized MG (gMG) with­in 18 months, where mus­cles through­out the body may be af­fect­ed, re­sult­ing in ex­treme fa­tigue and dif­fi­cul­ties with fa­cial ex­pres­sion, speech, swal­low­ing and mo­bil­i­ty.

The need for new treat­ment op­tions is ap­par­ent — giv­en the tox­i­c­i­ty of steroids and im­muno­sup­pres­sants and Soliris’ pro­hib­i­tive costs. While in­tra­venous im­munoglob­u­lin (IVIg) is used as a stop-gap, high costs, long in­fu­sions ac­com­pa­nied by headaches and sup­ply con­straints lim­it its broad­er ap­peal.

“FcRn an­tag­o­nists’ broad­ly ap­plic­a­ble mech­a­nism of ac­tion and safe and ef­fi­ca­cious clin­i­cal pro­file should sup­port their com­pet­i­tive edge and sup­port use in ear­li­er lines of ther­a­py. Giv­en ef­gar­tigi­mod’s lead to mar­ket and like­ly avail­abil­i­ty as both IV and SQ, we an­tic­i­pate that it will cap­ture the li­on’s share of the mar­ket,” Cowen an­a­lyst Yaron Wer­ber wrote in an April note.

The neona­tal Fc re­cep­tor (FcRn) plays a key role in pre­vent­ing the degra­da­tion of IgG an­ti­bod­ies. 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 con­di­tion). Drugs de­signed to in­hib­it FcRn, there­fore, are de­signed to de­crease to­tal IgG — cru­cial­ly path­o­gen­ic IgG — to treat pa­tients.

So­cial im­age: ar­genx

In­side Track: Be­hind the Scenes of a Ma­jor Biotech SPAC

Dr. David Hung and Michelle Doig are no strangers to the SPAC phenomenon. As Founder and CEO of Nuvation Bio, a biotech company tackling some of the greatest unmet needs in oncology, Dr. Hung recently took the company public in one of this year’s biggest SPAC related deals. And as Partner at Omega Funds, Doig not only led and syndicated Nuvation Bio’s Series A, but is now also President of the newly formed, Omega-sponsored, Omega Alpha SPAC (Nasdaq: OMEG; oversubscribed $138m IPO priced January 6, 2021).

Aduhelm OK 'bit­ter­sweet' for ALS ad­vo­cates; Con­trast­ing Covid-19 vac­cine read­outs; GSK joins TIG­IT bat­tle; 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 the busiest days of June now behind us, we’re starting to think seriously about the second half of the year. In August, we have scheduled a special report where Endpoints will compile a list of the 20 most influential R&D executives in biopharma. Know a luminary who should definitely be included? Nominate them now.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,800+ biopharma pros reading Endpoints daily — and it's free.

Who are the lu­mi­nar­ies dri­ving the biggest ad­vances in bio­phar­ma R&D? End­points News is ask­ing for your nom­i­na­tions for a spe­cial re­port

In biopharma, driving a drug to market is the ultimate goal — but none of that happens without a strong research and development program. At the most successful companies, those R&D efforts are spearheaded by true innovators in the field who are always looking for that next novel mechanism of action or breakthrough safety profile.

Now, Endpoints News is asking you to tell us who those guiding lights are.

Leen Kawas, Athira CEO

Biotech founder placed on leave as $400M Alzheimer's start­up idea comes un­der scruti­ny

Athira Pharma, the Alzheimer’s biotech that emerged out of obscurity last year and raised nearly $400 million for a dark-horse approach to treating neurodegeneration, has found itself in sudden turmoil.

On Tuesday evening, the company released a terse statement announcing that CEO and founder Leen Kawas had been placed on administrative leave while an independent review board investigated “actions stemming” from her doctoral research at Washington State University. Mark Litton, who joined the company as COO two years ago, will take over day-to-day operations, they said.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,800+ biopharma pros reading Endpoints daily — and it's free.

Bris­tol My­ers breaks the bank on Ei­sai's fo­late re­cep­tor ADC drug, lay­ing out more than $3B+ for rights

For years, innovation in oncology has been a crapshoot with Big Pharma — the whales at the table — dropping the big bucks for the key to the next generation of tumor fighters. Bristol Myers Squibb hasn’t exactly made a name for being an innovator in the space, but that doesn’t mean it won’t splash in when it sees a potential winner.

Now, with a massive check in hand, the drugmaker is willing to put its intuition to the test.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,800+ biopharma pros reading Endpoints daily — and it's free.

Michael Chambers (L) and John Ballantyne

Dana­her strikes deal to buy boom­ing next-gen man­u­fac­tur­er Alde­vron for $9.6B

Life sciences conglomerate Danaher Corp. $DHR has struck a deal to buy the fast-growing Aldevron, one of the world’s top manufacturers of hotly sought-after plasmid DNA, mRNA and recombinant proteins for the burgeoning world of vaccine and drugmakers pushing some game-changing technologies.

Buyout talks set the stage for Danaher to settle on a $9.6 billion cash pact to acquire the private Fargo, ND-based company — a key supplier for a disruptive new Covid vaccine as well as a host of gene and cell therapy and CRISPR gene editing players — founded by Michael Chambers and CSO John Ballantyne as a crew of 2 back in 1998.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Jeff Albers, Blueprint CEO

Blue­print Med­i­cines nabs 4th ap­proval in bid to­ward prof­itabil­i­ty

Blueprint Medicines’ push to profitability continues.

On Wednesday, the Cambridge biotech announced the FDA approved its longtime lead drug, Ayvakit, for advanced systemic mastocytosis, a group of debilitating rare diseases where one type of immune cell — mast cells — builds up uncontrollably in a particular organ. The decision came on the heels of Phase III trials showing that more than half of late-stage patients who received the drug responded to it and did so for just over three years.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,800+ biopharma pros reading Endpoints daily — and it's free.

Franz-Werner Haas, CureVac CEO (Christoph Schmidt/picture-alliance/dpa/AP Images)

UP­DAT­ED: Cure­Vac blames vari­ants as a close­ly-watched Covid vac­cine goes down in flames, fail­ing piv­otal study with woe­ful da­ta

CureVac was widely expected to come in with a late but likely late-stage winner in the race to develop new vaccines for the Covid-19 pandemic. Instead, late Wednesday, the German biotech said their mRNA candidate CVnCoV flat failed a pivotal trial — quashing any hopes for a quick entry in the blockbuster field and gutting their share price.

CVnCoV demonstrated an interim vaccine efficacy of 47% against COVID-19 disease of any severity and did not meet prespecified statistical success criteria. Initial analyses suggest age and strain dependent efficacy.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,800+ biopharma pros reading Endpoints daily — and it's free.

Al Sandrock, Biogen R&D chief (Biogen via YouTube)

Days af­ter con­tro­ver­sy greet­ed Bio­gen's block­buster Alzheimer's OK, the big biotech con­cedes a set­back on the tau front

Just days after triggering a maelstrom of controversy with their decision to launch an unproven Alzheimer’s drug with a $56,000 price, Biogen $BIIB is back with the latest data on its mid-stage tau drug.

And it’s not good.

The big biotech says that gosuranemab — targeted at tau, the second leading drug target in Alzheimer’s — flat failed its Phase II and will now be taken out and dumped in the mass grave for all but one other Alzheimer’s drug in the past generation.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,800+ biopharma pros reading Endpoints daily — and it's free.