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

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials.

Scoop: ARCH’s Bob Nelsen is back­ing an mR­NA up­start that promis­es to up­end the en­tire man­u­fac­tur­ing side of the glob­al busi­ness

For the past 2 years, serial entrepreneur Igor Khandros relied on a small network of friends and close insiders to supply the first millions he needed to fund a secretive project to master a new approach to manufacturing mRNA therapies.

Right now, he says, he has a working “GMP-in-a-box” prototype for a new company he’s building — after launching 3 public companies — which plans to spread this contained, precise manufacturing tech around the world with a set of partners. He’s raised $60 million, recruited some prominent experts. And not coincidentally, he’s going semi-public with this just as a small group of pioneers appears to be on the threshold of ushering in the world’s first mRNA vaccines to fight a worldwide pandemic.

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Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

Blueprint CEO Jeff Albers (file photo)

Blue­print plots re­turn to FDA with new Ay­vak­it da­ta in rare con­di­tion — and the an­a­lysts cheer

Over a decade after launch, Blueprint Medicines nabbed the first approval for their first drug earlier this year. Now, as they move forward with a Roche-partnered global launch, they’re touting data that could push them into more patients.

The Jeff Albers-led Cambridge biotech released their full pivotal data for Ayvakit in patients with advanced systemic mastocytosis. In one 53-person study, they showed that 76% of patients responded to the drug, 36% had complete responses and that on average their responses lasted for just over 3 years. A smaller, 32-patient study had a 75% response rate and most were still responding after 10.4 months, the last follow-up.

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Anthony Coyle (Repertoire)

Flag­ship's merged biotech Reper­toire nets ex-Pfiz­er CSO An­tho­ny Coyle as R&D chief

Flagship is building a big-name C-suite at its new, $220 million merged biotech.

Repertoire Immune Medicines, which already boasts former Bioverativ chief John Cox as its CEO, announced yesterday that Anthony Coyle, the former Pfizer CSO and the founding CEO of Pandion, will join as their head of R&D.

“As we progress clinical trials for our multi-clonal T cell candidates in immuno-oncology, Tony’s deep expertise in cellular immunology and novel therapeutic development will help us achieve our vision of creating a new class of transformative medicines for patients,” Cox said in a statement.

President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists. HHS con­tin­ues to claim Azar “will de­fer com­plete­ly to the FDA"

President Donald Trump, who seems intent on announcing a Covid-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the FDA and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Trump — who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA — will take matters into his own hands, running roughshod over the usual regulatory process.