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.

UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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