Reshma Kewalramani, Vertex CEO (Vertex)

A year out from FDA ap­proval, Ver­tex looks to ex­pand top-sell­ing CF drug to pe­di­atrics

About a year af­ter get­ting the FDA thumbs-up for its block­buster cys­tic fi­bro­sis drug Trikaf­ta, Ver­tex is pick­ing up where it left off.

The Boston-based biotech read out pos­i­tive re­sults from a Phase III study in­volv­ing chil­dren ages 6 to 11, and an­nounced plans to file for a sup­ple­men­tal NDA lat­er this year. Pre­vi­ous­ly, the triplet reg­i­men was on­ly avail­able to pa­tients 12 and up.

Trikaf­ta, Ver­tex’s $VRTX fourth CF drug, is de­signed for those with at least one F508del mu­ta­tion in the CFTR gene. It cov­ers about 90% of CF pa­tients, un­like the com­pa­ny’s Ka­ly­de­co, which on­ly cov­ers 6% of Amer­i­cans with CF, ac­cord­ing to a STAT re­port. With­in weeks of Trikaf­ta’s Oc­to­ber 2019 launch, it be­came Ver­tex’s top-sell­ing drug. Quar­ter­ly US sales hit $420 mil­lion by the end of Jan­u­ary.

The win al­lowed for­mer CEO Jef­frey Lei­den to step down on a high note, pass­ing the torch to cur­rent CEO Resh­ma Ke­wal­ra­mani. Lei­den shift­ed over to ex­ec­u­tive chair­man of the com­pa­ny.

Car­men Boz­ic

“Our aim is to ex­tend el­i­gi­bil­i­ty to all pa­tients who may ben­e­fit from this trans­for­ma­tive med­i­cine, and the pos­i­tive re­sults from the study in chil­dren ages 6 through 11 years old al­lows us to take an­oth­er step for­ward to­ward this goal,” Car­men Boz­ic, Ver­tex CMO and EVP of glob­al med­i­cines de­vel­op­ment and med­ical af­fairs, said in a state­ment.

CF is char­ac­ter­ized by the build-up of sticky mu­cus in the lungs, di­ges­tive sys­tem and oth­er or­gans. It’s caused by a de­fec­tive pro­tein that re­sults from mu­ta­tions in the CFTR gene — the most com­mon mu­ta­tion be­ing F508del. Ac­cord­ing to Ver­tex, a Phase III study with 66 chil­dren pro­duced safe­ty da­ta “con­sis­tent with those ob­served in pre­vi­ous Phase III stud­ies.”

The drug cleared pri­ma­ry safe­ty and tol­er­a­bil­i­ty end­points, and showed “mean­ing­ful im­prove­ment” across sec­ondary ef­fi­ca­cy end­points, in­clud­ing per­cent pre­dict­ed forced ex­pi­ra­to­ry vol­ume in 1 sec­ond (ppFEV 1, a mark­er of cys­tic fi­bro­sis lung dis­ease pro­gres­sion), sweat chlo­ride, Cys­tic Fi­bro­sis Ques­tion­naire Re­vised (CFQ-R) res­pi­ra­to­ry do­main score, and body mass in­dex (BMI) through 24 weeks of treat­ment.

De­spite the an­nounce­ment, Ver­tex’s shares dropped 2.8% on Thurs­day, clos­ing at $255.65 per share.

In April, the com­pa­ny faced crit­i­cism from cost-ef­fec­tive­ness watch­dog ICER that its CF drugs were too ex­pen­sive. Trikaf­ta is priced at more than $311,000 an­nu­al­ly, or around $24,000 for a month’s sup­ply. ICER sug­gest­ed dis­counts of up to 77% to match the prices of Ver­tex’s CF drugs with their clin­i­cal val­ue.

“De­spite be­ing trans­for­ma­tive ther­a­pies, the prices set by the man­u­fac­tur­er – cost­ing many mil­lions of dol­lars over the life­time of an av­er­age pa­tient – are out of pro­por­tion to their sub­stan­tial ben­e­fits,” ICER CMO David Rind said in a state­ment. “When a man­u­fac­tur­er has a mo­nop­oly on treat­ments and is aware that in­sur­ers will be un­able to refuse cov­er­age, the lack of usu­al coun­ter­bal­anc­ing forces can lead to ex­ces­sive prices,” he added lat­er.

Days af­ter Trikaf­ta’s FDA ap­proval, Ab­b­Vie an­nounced plans to snag a port­fo­lio of CF drugs from Gala­pa­gos in a $245 mil­lion deal, and bring in a pre­clin­i­cal CFTR po­ten­tia­tor com­pound from the Cys­tic Fi­bro­sis Foun­da­tion. The Gala­pa­gos da­ta looked weak com­pared to Ver­tex’s, but Ab­b­Vie seemed stead­fast. It cur­rent­ly has a com­bo with one po­ten­tia­tor and two cor­rec­tor mol­e­cules in Phase I de­vel­op­ment.

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

Re­gen­eron's Evkeeza shows promise in curb­ing high triglyc­erides, but will ge­net­ic dis­par­i­ties lim­it use?

When Regeneron scored an early approval for lipid lowering antibody Evkeeza back in February, the drugmaker cracked open a new pathway to lower abnormally high cholesterol levels. Now, Regeneron is chasing high triglycerides as well with some promising mid-stage data — but will genetic restrictions limit the drug’s use?

Regeneron’s Evkeeza (evinacumab) cut median triglyceride levels by more than 800 mg/dL (57%) in patients with a rare disorder causing abnormally high triglyceride levels compared with an overall increase of 50 mg/dL (1.8%) in participants on placebo, according to Phase II data presented Sunday at the virtual American College of Cardiology meeting.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; and more

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I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

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As­traZeneca's Farx­i­ga missed big on Covid-19 study, but it's tak­ing SGLT2 safe­ty da­ta as a sil­ver lin­ing

AstraZeneca hasn’t seen many setbacks in recent months for SGLT2 inhibitor Farxiga, which broke ground in heart failure and kidney disease regardless of diabetes diagnosis. But the British drugmaker had to admit defeat in taking Farxiga into Covid-19, but follow-up results add a bit of a silver lining to that trial’s safety data.

Of hospitalized Covid-19 patients dosed with AstraZeneca’s Farxiga, 11.2% experienced an organ failure or died after 30 days of therapy compared with 13.8% of those given placebo, according to follow-up data from the DARE-19 study revealed Sunday at the virtual American College of Cardiology meeting.

Pfiz­er, Bris­tol My­er­s' Eliquis flops in post-heart surgery pa­tients, spurring an 'un­ex­plained sig­nal' in cer­tain deaths

Pfizer and Bristol Myers Squibb’s non-warfarin blood thinner Eliquis has raced out to become the most prescribed drug of its class on the market — even overtaking warfarin’s long-time lead. But in tricky-to-treat patients after a valve replacement, an investigator-sponsored study couldn’t turn up benefit and raised a troubling safety signal.

Eliquis failed to show benefit over standard of care in preventing serious clinical outcomes after a transaortic valve replacement (TAVR) and was linked to an “unexplained signal” in a subset of populations with a higher rate of non-CV deaths who did not need blood thinners apart from the surgery, according to data presented Saturday at the virtual American College of Cardiology meeting.

Vas Narasimhan (Photographer: Simon Dawson/Bloomberg via Getty Images)

No­var­tis whiffs on En­tresto study af­ter heart at­tacks — but that does­n't mean it's go­ing down qui­et­ly

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.

Michael Dell (Richard Drew, AP Images)

'Dude, you're get­ting a Del­l' — as a new deep-pock­et biotech in­vestor

What happens when you marry longtime insiders in the global biotech VC game with the family fund of tech billionaire Michael Dell, a synthetic biology legend out of MIT and Harvard and the former director of the NCI?

Today, the answer is a newly financed, $200 million biotech SPAC now cruising the industry for a top player interested in finding a short cut to Nasdaq.

Orion Biotech Opportunities priced their blank check company today, raising $200 million with Dell’s multibillion-dollar MSD group’s commitment on investing another $20 million in a forward-purchase agreement.

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Gene ther­a­py from Bio­gen's $800M buy­out flops in mid-stage study, deal­ing blow to new am­bi­tions

The #2 candidate from Biogen’s $800 million ocular gene therapy buyout has failed in a mid-stage trial, dealing an early blow to the big biotech’s plans to revitalize its pipeline with new technologies.

Biogen announced that the candidate, an experimental treatment for a rare and progressive form of blindness called X-linked retinitis pigmentosa (XLRP), failed to sufficiently improve vision in patients’ treated eye — patients only received an injection in one eye — after a year, on a standard scale, compared to their untreated eye. The company said they saw “positive trends” on several secondary endpoints, including visual acuity, but declined to say whether the trial actually hit any of those endpoints.

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In­cyte’s PD-(L)1 in­hibitor head­ed for an ODAC show­down next month

The FDA’s Oncologic Drugs Advisory Committee will spend a half day on June 24 reviewing Incyte’s PD-(L)1 inhibitor retifanlimab as a treatment for locally advanced or metastatic squamous carcinoma of the anal canal (SCAC) for those who have progressed on or who are intolerant of platinum-based chemotherapy.

The eighth PD-(L)1 entrant in January nabbed a priority review and an orphan designation from the FDA, which sets the agency’s final decision date as July 25.