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.

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.

President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists

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.

#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.

#ES­MO20: Bris­tol My­ers marks Op­di­vo's sec­ond ad­ju­vant win — eye­ing a stan­dard of care gap

Moving into earlier and earlier treatment lines, Bristol Myers Squibb is reporting that adjuvant treatment with Opdivo has doubled the time that esophageal or gastroesophageal junction cancer patients stay free of disease.

With the CheckMate-577 data at ESMO, CMO Samit Hirawat said, the company believes it can change the treatment paradigm.

While a quarter to 30% of patients typically achieve a complete response following chemoradiation therapy and surgery, the rest do not, said Ronan Kelly of Baylor University Medical Center. The recurrence rate is also high within the first year, Hirawat added.

UP­DAT­ED: Two wild weeks for Grail end in $8B Il­lu­mi­na buy­out

Grail’s whirlwind two weeks have ended in the wealthy arms of its former founder and benefactors.

Illumina has shelled out $8 billion to reacquire the closely-watched liquid biopsy startup they spun out just 5 years ago and sold off much of its shares just 3 years ago. The deal comes nearly two weeks after the well-heeled startup filed for a potentially massive IPO — one that was disrupted just a week later when Bloomberg reported that Illumina was in talks to buy their former spinout for up to $8 billion.

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Roche vaults to the front of the NL­RP3 clin­i­cal race, pay­ing $448M up­front to bag In­fla­zome

Roche is going all in on NLRP3.

The pharma giant is putting down $448 million (€380 million) upfront to snatch Novartis-backed Inflazome, which makes it a clinical player in the space overnight.

Dublin and Cambridge, UK-based Inflazome is the second NLRP3-focused biotech Roche has acquired in less than two years, and although no numbers were disclosed in the Jecure buyout, this is almost certainly a much larger deal.

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Anthony Fauci (AP Images)

A press of­fi­cer at An­tho­ny Fau­ci’s NI­AID was un­masked as a hard-right Covid troll. He just re­tired to­day

William B Crews had been a public affairs specialist at the NIH’s National Institute of Allergy and Infectious Diseases.

That ended today when he informed the agency of his decision to retire, after he was identified as the managing editor at RedState, a prominent Trump loyalist website.

Crews’ RedState duties are performed under the alias streiff. While enjoying the benefits of pseudonymity, he disparaged and worked against NIAID with an incendiary level of rhetoric in the midst of a pandemic.

Donald Trump, AP

Covid-19 roundup: Trump sug­gests Pfiz­er vac­cine could be first ap­proved; VBI Vac­cines inks de­vel­op­ment deal with Cana­da

President Donald Trump commented Monday morning that Pfizer’s Covid-19 vaccine candidate could be the first to win approval by regulators.

During an interview on a Fox News’ morning show, the president said Pfizer was doing “very well” when asked which candidate could be approved, according to a Reuters report. He added that J&J could follow up afterward, saying “they’ll probably be a little later.”

Is­raeli biotech rais­es $57M to go where cur­rent BRAF in­hibitors can't, with back­ing from No­var­tis, SR One

For the blockbuster potential of Novartis’ Tafinlar and Pfizer’s Braftovi, all the BRAF inhibitors on the market so far only target V600 mutations — which accounts for roughly 50% of patients.

Israeli biotech Novellus now has $57 million to develop a drug that they say can help the other 50% who have everything else.

The Series C will fund a Phase II trial for PLX-8394, a “paradox breaker” that could block RAF without activating MAPK signaling. In a Phase I trial, a patient with a BRAF fusion saw their tumor go away after taking the drug, allowing Novellus to hit the ground running.