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.

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