My­ovan­t's re­l­u­golix clears first uter­ine fi­broids PhI­II test, but com­pe­ti­tion from Ab­b­Vie/Neu­ro­crine makes in­vestors jit­tery

Vivek Ra­maswamy’s bet on Take­da’s re­l­u­golix has worked — sort of.

Vivek Ra­maswamy

Less than three years af­ter the pro­lif­ic deal­mak­er spawned My­ovant as part of his um­brel­la of ‘Vants’ with a record $218 mil­lion IPO, the treat­ment in-li­censed from the Japan­ese drug­mak­er passed muster in a late-stage study in women with uter­ine fi­broids, which are com­mon non-can­cer­ous fe­male re­pro­duc­tive tract tu­mors. But in­vestors were not quite as im­pressed as the com­pa­ny’s shares $MY­OV tum­bled in ear­ly Tues­day trad­ing.

The oral drug, which is an an­tag­o­nist of the go­nadotropin-re­leas­ing hor­mone (GnRH) re­cep­tor, is de­signed to sup­press es­tro­gen pro­duc­tion in women. It is be­ing test­ed in twin piv­otal stud­ies in­volv­ing women with uter­ine fi­broids and heavy men­stru­al bleed­ing, called LIB­ER­TY 1 and LIB­ER­TY 2.

My­ovant on Tues­day un­veiled the re­sults of the first Phase III tri­al, which en­rolled 388 women and test­ed re­l­u­golix (40 mg) in com­bi­na­tion with fe­male hor­mones estra­di­ol (1 mg) and norethin­drone ac­etate (0.5 mg). In the tri­al, pa­tients re­ceived ei­ther re­l­u­golix com­bi­na­tion ther­a­py for 24 weeks; re­l­u­golix monother­a­py for 12 weeks fol­lowed by re­l­u­golix com­bi­na­tion ther­a­py for the next 12 weeks; or place­bo once dai­ly for 24 weeks.

In the study, 73.4% of women re­ceiv­ing once-dai­ly oral re­l­u­golix com­bi­na­tion ther­a­py achieved the re­spon­der cri­te­ria com­pared with 18.9% of women re­ceiv­ing place­bo (p < 0.0001) — meet­ing the main goal. A re­sponse was de­fined as a men­stru­al blood loss vol­ume of less than 80 mL and a 50% or greater re­duc­tion from base­line in men­stru­al blood loss vol­ume dur­ing the last 35 days of the 24-week treat­ment pe­ri­od. On av­er­age, women re­ceiv­ing re­l­u­golix com­bi­na­tion ther­a­py al­so ex­pe­ri­enced an 84.3% re­duc­tion in men­stru­al blood loss from base­line, which was a key sec­ondary end­point.

Ab­b­Vie $AB­BV and Neu­ro­crine Bio­sciences’ $NBIX ther­a­py elagolix (brand­ed as Orilis­sa), which was ap­proved last year to treat en­dometrio­sis, is al­so be­ing eval­u­at­ed for use in uter­ine fi­broids. It is has a sim­i­lar mech­a­nism of ac­tion com­pared to re­l­u­golix but is tak­en twice-dai­ly. The com­pa­nies have re­port­ed da­ta from two piv­otal six-month stud­ies. In one late-stage study, 68.5% (p<0.001) of elagolix-treat­ed women with uter­ine fi­broids achieved clin­i­cal re­sponse com­pared to place­bo (8.7%), in the sec­ond tri­al 76.2% (p<0.001) of elagolix-treat­ed women with uter­ine fi­broids achieved clin­i­cal re­sponse com­pared to place­bo (10.1%). A reg­u­la­to­ry sub­mis­sion for elagolix in uter­ine fi­broids is an­tic­i­pat­ed in mid-2019.

Phil Nadeau

“Re­l­u­golix will fol­low Neu­ro­crine’s GnRH an­tag­o­nist Orilis­sa to the U.S. mar­ket. How­ev­er, re­l­u­golix has cer­tain dif­fer­en­ti­at­ing fea­tures (once-dai­ly dos­ing, full es­tro­gen sup­pres­sion) that should al­low it to cap­ture share, par­tic­u­lar­ly in sit­u­a­tions such as uter­ine fi­broids or se­vere en­dometrio­sis where high GnRH sup­pres­sion is nec­es­sary,” Cowen’s Phil Nadeau wrote in a note in Feb­ru­ary, es­ti­mat­ing that in 2025 re­l­u­golix will gen­er­ate $1.15 bil­lion in uter­ine fi­broid sales.

Ob­sE­va $OB­SV is al­so cur­rent­ly de­vel­op­ing a GnRH re­cep­tor an­tag­o­nist called Lin­zagolix for uter­ine fi­broids — da­ta from its late-stage study is ex­pect­ed in the fourth quar­ter of this year.

“(G)yne­col­o­gists re­in­forced our the­sis that the clin­i­cal pro­file of the GnRH an­tag­o­nists could ad­dress a sig­nif­i­cant un­met need in uter­ine fi­broids and en­dometrio­sis, and that giv­en the het­ero­gene­ity in pa­tient re­sponse, there is like­ly to be a de­mand for all the three Gn­RHs”, SVB Leerink an­a­lysts wrote in a note pub­lished last month.

Da­ta from LIB­ER­TY 2 is ex­pect­ed in the third quar­ter of 2019, and if pos­i­tive, the two tri­als will form the ba­sis of a mar­ket­ing ap­pli­ca­tion that is planned for the fourth quar­ter, My­ovant said.

My­ovant’s in­vestors are not quite as en­thu­si­as­tic. Ab­b­Vie (our Go­liath) will file its mar­ket­ing ap­pli­ca­tion in the com­ing months, and if ap­proved will have some time to es­tab­lish it­self be­fore My­ovant (our David) makes it to the mar­ket, by which time it will be much hard­er for the small­er play­er to take a bite out of Ab­b­Vie’s mar­ket share. My­ovant’s stock $MY­OV was down about 29% at $12.22 in morn­ing trad­ing.

Baird’s Bri­an Sko­r­ney is­sued a glow­ing re­view of the My­ovant da­ta. “The first Phase 3 da­ta set in uter­ine fi­broids hit all the check box­es for an ap­prov­able, com­pet­i­tive pro­gram. We think the stock free-fall re­flects a sell-the-news dy­nam­ic, ex­ac­er­bat­ed by an ab­sence of ef­fi­ca­cy dif­fer­en­ti­a­tion and fi­nanc­ing con­cerns. We are buy­ers on the dip and con­tin­ue to be­lieve re­l­u­golix has block­buster po­ten­tial in uter­ine fi­broids and en­dometrio­sis,” he said in note on Tues­day.

“But I think the over­ar­ch­ing pres­sure on the stock is due to the fi­nanc­ing needs ahead of a launch that is prob­a­bly ~2 years away,” he added in an email to End­points News.

Uter­ine fi­broids are al­most al­ways be­nign tu­mors that emerge in or on the mus­cu­lar walls of the uterus. They can cause symp­toms such as ab­nor­mal uter­ine bleed­ing, heavy or painful pe­ri­ods, ane­mia, ab­dom­i­nal pain, back­ache, in­creased ab­dom­i­nal girth and bloat­ing, uri­nary fre­quen­cy or re­ten­tion, con­sti­pa­tion or painful defe­ca­tion, preg­nan­cy loss, painful in­ter­course and, in some cas­es, in­fer­til­i­ty. Be­tween 20% to 80% of women de­vel­op fi­broids by the time they reach age 50, ac­cord­ing to HHS es­ti­mates.

Lynn Seely

Take­da $TAK has an eq­ui­ty stake in My­ovant, which is al­so eval­u­at­ing re­l­u­golix as a treat­ment for en­dometrio­sis in women, as well as ad­vanced prostate can­cer in men. The biotech is run by Lynn Seely, the for­mer CMO of Medi­va­tion.

The in­fec­tious for­mer hedge fund man­ag­er Ra­maswamy has whipped up a pletho­ra of com­pa­nies un­der his um­brel­la firm Roivant, by con­vinc­ing in­vestors that lu­cra­tive re­turns can be made by tak­ing ex­per­i­men­tal drugs gath­er­ing dust on big phar­ma shelves all the way across the fin­ish line. His first big bet on Alzheimer’s/de­men­tia as­sets — much like every­thing else in the bat­tered field — failed spec­tac­u­lar­ly at his sem­i­nal Ax­o­vant $AX­ON}, but he has rein­vig­o­rat­ed the com­pa­ny in­to a gene-ther­a­py play­er. Mean­while, his en­thu­si­asm for the strat­e­gy has not with­ered, as he has birthed var­i­ous oth­er ‘Vants’ fo­cus­ing on dif­fer­ent ill­ness­es and ther­a­peu­tic ap­proach­es.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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CBO: Medicare ne­go­ti­a­tions will ham­per drug de­vel­op­ment more than pre­vi­ous­ly thought

As President Biden’s Build Back Better Act — and, with it, potentially the Democrats’ last shot at major drug pricing reforms in the foreseeable future — remains on life support, the Congressional Budget Office isn’t helping their case.

The CBO last week released a new slide deck, outlining an update to its model on how Medicare negotiations might take a bite out of new drugs making it to market. The new model estimates a 10% long-term reduction in the number of new drugs, whereas a previous CBO report from August estimated that 8% fewer new drugs will enter the market over 30 years.

Joshua Brumm, Dyne Therapeutics CEO

FDA or­ders DMD tri­al halt, rais­ing ques­tions about a whole class of promis­ing drugs

Dyne Therapeutics’ stock took a nasty hit this morning after the biotech put out word that the FDA had slapped a clinical hold on their top program for Duchenne muscular dystrophy. And now speculation is bouncing around Biotwitter that there could be a class effect at work here that would implicate other drug developers in the freeze.

Dyne execs didn’t have a whole lot to say about why the FDA sidelined their IND for DYNE-251 in DMD while “requesting additional clinical and non-clinical information for” the drug.

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Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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Chamath Palihapitiya and Pablo Legorreta

Bil­lion­aires Chamath Pal­i­hapi­tiya and Pablo Legor­re­ta hatch an $825M SPAC for cell ther­a­py biotech

Three years after Royalty Pharma chief Pablo Legorreta led a group of investors to buy up a pair of biotechs and create a new startup called ProKidney, the biotech is jumping straight into an $825 million public shell created by SPAC king and tech billionaire Chamath Palihapitiya.

ProKidney was founded 6 years ago but really got going at the beginning of 2019 with the $62 million acquisition of inRegen, which was working on an autologous — from the patient — cell therapy for kidney disease. After extracting kidney cells from patients, researchers expand the cells in the lab and then inject them back into patients, aiming to restore the kidneys of patients suffering from CKD.

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Michel Vounatsos, Biogen CEO (Credit: World Economic Forum/Ciaran McCrickard)

An un­ortho­dox pro­pos­al for Bio­gen's Medicare-man­dat­ed Aduhelm tri­al

Biogen has gone full blitz since Medicare announced it would only cover its new Alzheimer’s drug when used in clinical trials, accusing the agency of discriminating against Alzheimer’s patients and trying to get physicians to change regulators’ minds.  Critics, meanwhile, cheered what they see as a necessary wall protecting payers and patients from an unproven and unsafe drug.

Far less attention, though, has gone to what a Medicare-funded clinical trial would actually look like. Biogen has operated as if it would be a standard late-stage Alzheimer’s trial, enrolling a couple thousand patients and giving half placebo.

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