Mer­ck, the late­com­er to the Covid-19 vac­cine race, said to­day that it will push its first can­di­date in­to the clin­ic this quar­ter and move the oth­er one there by the end of the year.

They are like­ly go­ing to be sin­gle-dose reg­i­mens, Mer­ck not­ed, as op­posed to the prime-boost ap­proach be­ing adopt­ed in Phase III stud­ies by Mod­er­na, Pfiz­er/BioN­Tech and As­traZeneca/Ox­ford.

Roger Perl­mut­ter

For the first time since the com­pa­ny threw its name in­to the hat with one li­cens­ing deal and an ac­qui­si­tion, R&D chief Roger Perl­mut­ter al­so of­fered his thoughts on how the fron­trun­ners are do­ing, why he didn’t go with an mR­NA ap­proach de­spite a long­stand­ing part­ner­ship with Mod­er­na, and what gaps Mer­ck’s pro­grams might fill.

Bot­tom line: There will like­ly still be plen­ty to do in 2021, when Mer­ck ex­pects to have avail­able hun­dreds of mil­lions of dos­es that it’s now man­u­fac­tur­ing at risk.

“There’s rea­son to be­lieve that mul­ti­ple vac­cines will be re­quired in or­der to man­age this ex­tra­or­di­nary glob­al pan­dem­ic, in par­tic­u­lar when one thinks about the het­ero­gene­ity of the pop­u­la­tion that we want to vac­ci­nate,” he said on Mer­ck’s Q2 earn­ings call.

Both of the can­di­dates his team is now ad­vanc­ing are vi­ral vec­tors that de­liv­er the gene for the spike pro­tein of the coro­n­avirus to cells. Themis, which is now a Mer­ck sub­sidiary, us­es a measles vec­tor; it will move in­to Phase I in Q3. The one li­censed from In­ter­na­tion­al Aids Vac­cine Ini­tia­tive, mean­while, us­es the re­com­bi­nant vesic­u­lar stom­ati­tis virus tech­nol­o­gy de­ployed for Mer­ck’s ap­proved Ebo­la vac­cine. Backed with a $38 mil­lion BAR­DA grant, the pro­gram will en­ter the clin­ic lat­er this year.

Clin­i­cal da­ta from oth­er vac­cine de­vel­op­ers sug­gest the spike pro­tein in­duces good im­mune re­spons­es — some­thing that was not guar­an­teed.

“We have to say that from our start­ing po­si­tion, know­ing very lit­tle about SARS-CoV-2 at the be­gin­ning, the re­sults we have seen thus far from a va­ri­ety of ear­ly stud­ies, Phase I stud­ies, are as good as one could hope for, re­al­ly,” Perl­mut­ter said.

The speed en­abled by mR­NA tech­nol­o­gy has been crit­i­cal for that. But look­ing at the long game, Mer­ck has oth­er con­cerns: Can they make a vac­cine po­tent enough that one dose is suf­fi­cient? What about one that can be ad­min­is­tered oral­ly? Do you need dif­fer­ent vac­cines for dif­fer­ent pop­u­la­tions, say the el­der­ly ver­sus some­one in their 20s?

When asked why he was so con­fi­dent about sin­gle-dose ac­tiv­i­ty, he went deep­er in­to the sci­ence:

We have a lot of con­fi­dence in the sin­gle dose ac­tiv­i­ty of both vac­cines be­cause these are repli­cat­ing vac­cines. So they repli­cate in you. They are very po­tent im­muno­gens, and they have sin­gle ad­min­is­tra­tion ac­tiv­i­ty in oth­er set­tings. So of course with the V590, that’s the vesic­u­lar stom­ati­tis virus vac­cine, that’s been demon­strat­ed for Ebo­la virus dis­ease very ef­fec­tive­ly. A sin­gle dose, you know, pro­vides in the field — in the set­ting of civ­il strife of a large mag­ni­tude — greater than 97.5% ef­fi­ca­cy in a sin­gle dose. Now I can’t tell you that that’s ex­act­ly how it will be­have when we put a dif­fer­ent gene, in this case SARS-CoV-2 spike pro­tein en­cod­ing nu­cle­ic acids, in­to the con­struct. But the in­ter­est­ing thing about the VSV plat­form is that this is ac­tu­al­ly a vac­cine in which the spike pro­tein be­comes part of the vac­cine. The repli­ca­tion of the virus is com­plete­ly de­pen­dent on the spike pro­tein, it be­comes the en­ve­lope pro­tein of the vac­cine. Which is — it’s dif­fer­ent from sim­ply ex­press­ing the pro­tein wher­ev­er one ex­press­es it. That has big ef­fects, and pre­clin­i­cal­ly the mag­ni­tude of the re­sponse fol­low­ing sin­gle ad­min­is­tra­tion is very im­pres­sive. Sim­i­lar­ly the measles plat­form has been shown in a va­ri­ety of dif­fer­ent set­tings, most re­cent­ly with re­spect to the chikun­gun­ya ad­min­is­tra­tion, to be a very po­tent im­muno­gen.

The plan is to elu­ci­date the prop­er­ties of each in the up­com­ing clin­i­cal tri­als and fig­ure out the best de­vel­op­ment paths for both, rather than choos­ing one over the oth­er.

On top of its vac­cine work, Mer­ck dis­closed to­day that it’s plan­ning to send MK-4482, the Ridge­back-part­nered an­tivi­ral, in­to large-scale Phase III stud­ies in Sep­tem­ber. — Am­ber Tong and Ja­son Mast

Chi­na-backed hack­ers tried to steal Mod­er­na’s Covid-19 re­search, per of­fi­cial

Ear­li­er this week, Mod­er­na ac­knowl­edged it had re­moved sig­nage around its Nor­wood, MA man­u­fac­tur­ing plant due to un­spec­i­fied se­cu­ri­ty is­sues. Now, the cul­prit has ap­par­ent­ly emerged, and it doesn’t come as a sur­prise.

Chi­nese-backed hack­ers at­tempt­ed to steal some of Mod­er­na’s Covid-19 vac­cine re­search, ac­cord­ing to an anony­mous US se­cu­ri­ty of­fi­cial cit­ed by Reuters. The of­fi­cial did not pro­vide fur­ther de­tails, and the FBI and HHS de­clined to iden­ti­fy which com­pa­nies had been the tar­get of Chi­nese es­pi­onage.

The rev­e­la­tion comes a week af­ter the New York Times re­port­ed that the US Jus­tice De­part­ment had for­mal­ly in­dict­ed a pair of Chi­nese na­tion­als and ac­cused them of plot­ting to steal tech IP from a wide range of Amer­i­can com­pa­nies, in­clud­ing those work­ing on vac­cines. Ac­cord­ing to the in­dict­ment, the in­di­vid­u­als “con­duct­ed re­con­nais­sance on the com­put­er net­work of a Mass­a­chu­setts biotech firm pub­licly known to be re­search­ing a po­ten­tial COVID-19 vac­cine” on Jan­u­ary 27.

Re­con­nais­sance can mean a va­ri­ety of things, per cy­ber­se­cu­ri­ty ex­perts cit­ed by Reuters, in­clud­ing prob­ing web­sites for vul­ner­a­bil­i­ties and search­ing for im­por­tant ac­counts.

Mod­er­na re­moved sev­er­al signs around its Nor­wood plant a cou­ple months ago, but on­ly ad­dressed the is­sue af­ter the Boston Globe re­port­ed the com­pa­ny had al­so cov­ered up the sign on its head­quar­ters in what ap­peared to be white shrink wrap. Com­pa­ny spokes­peo­ple re­spond­ed vague­ly to those in­quiries.

Ray Jor­dan

“About two months ago, much of the sig­nage there was ei­ther ad­just­ed or re­moved out of an abun­dance of cau­tion for se­cu­ri­ty and for the safe­ty of our em­ploy­ees once it was clear that the pro­duc­tion fa­cil­i­ty would be­come a pri­ma­ry man­u­fac­tur­ing point for our vac­cine can­di­date,” chief cor­po­rate af­fairs of­fi­cer Ray Jor­dan told the Globe on Tues­day. “That was with­out any spe­cif­ic se­cu­ri­ty threats pre­cip­i­tat­ing the ac­tion.”

Rus­sia has al­so been ac­cused by the US, UK and Cana­di­an gov­ern­ments of at­tempt­ing to steal Covid-19 vac­cine da­ta from west­ern drug­mak­ers. It re­mains un­clear what, if any, in­for­ma­tion had been stolen, how­ev­er.

Mod­er­na this week launched a piv­otal Phase III study to de­ter­mine whether or not two 100 µg dos­es of their mR­NA vac­cine can pre­vent Covid-19 symp­toms from man­i­fest­ing. The com­pa­ny has emerged as one of the lead­ers in the vac­cine race, and BAR­DA com­mit­ted $472 mil­lion to help get that tri­al off the ground and scale up pro­duc­tion. — Max Gel­man

Remde­sivir buoys a down quar­ter for Gilead

The Covid-19 pan­dem­ic hit Gilead hard in the sec­ond quar­ter, but the phar­ma com­pa­ny ex­pects that to change for the bet­ter thanks to remde­sivir.

Jo­han­na Merci­er

Af­ter an­nounc­ing a 10 per­cent drop in sales in a quar­ter­ly earn­ings call with in­vestors Thurs­day af­ter­noon, Gilead re­vised its 2020 rev­enue pro­jec­tions up­ward, fore­cast­ing as much as $2.8 bil­lion more in year-end yield. Huge de­mand for remde­sivir is the biggest rea­son, as CCO Jo­han­na Merci­er hopes to meet the glob­al need by Oc­to­ber, ac­cord­ing to a Wall Street Jour­nal re­port.

Gilead re­ceived emer­gency FDA ap­proval for remde­sivir to treat Covid-19 back in May, with the com­pa­ny do­nat­ing treat­ments to the US gov­ern­ment for dis­tri­b­u­tion. The phar­ma start­ed sell­ing the drug this month, charg­ing $3,120 per course in the US and $2,340 in the EU.

The de­part­ment of Health and Hu­man Ser­vices makes up for al­most all of Gilead’s remde­sivir sales, as HHS sec­re­tary Alex Azar an­nounced a pur­chase of 500,000 cours­es of the drug on June 29. This ac­counts for all Ju­ly pro­duc­tion and 90 per­cent of pro­duc­tion in each of Au­gust and Sep­tem­ber.

SVB Leerink’s Ge­of­frey Porges cit­ed this HHS con­tract as a rea­son for op­ti­mism, ex­pect­ing Gilead to re­bound lat­er this year.

Due to remde­sivir’s com­pli­cat­ed man­u­fac­tur­ing process, Gilead has strug­gled to keep up with ear­ly de­mand for the drug. The pan­dem­ic has al­so af­fect­ed sup­ply chains around the world, and Gilead has not gone un­touched in this re­gard.

Dur­ing the earn­ings call, Gilead said it ex­pects to sell about one mil­lion to 1.5 mil­lion remde­sivir treat­ments in the sec­ond half of 2020. With these sales po­ten­tial­ly off­set­ting sec­ond-quar­ter loss­es, Gilead projects rev­enue to fall be­tween the $23.3 bil­lion and $25 bil­lion range, up from $21.8-22.2 bil­lion.

The Wall Street Jour­nal al­so cit­ed an an­a­lyst from Cred­it Su­isse who not­ed that Gilead is in­di­cat­ing full remde­sivir sales to be around $3 bil­lion and $4.5 bil­lion.

Over­all, Gilead post­ed a $3.34 bil­lion loss in the sec­ond quar­ter, large­ly dri­ven by ex­pens­es re­lat­ed to their $4.9 bil­lion ac­qui­si­tion of Forty Sev­en back in March. Be­cause Covid-19 al­so af­fect­ed how and when pa­tients de­cid­ed to seek rou­tine health care, sales for Gilead’s Bik­tarvy and De­scovy were al­so down for the quar­ter. — Max Gel­man

Japan pur­chas­es 120 mil­lion dos­es of Pfiz­er/BioN­Tech vac­cine can­di­date

The Covid-19 vac­cine can­di­date be­ing de­vel­oped by Pfiz­er and BioN­Tech has found a new buy­er — Japan.

The two com­pa­nies an­nounced Fri­day morn­ing that the Japan­ese gov­ern­ment has agreed to ac­quire 120 mil­lion dos­es of their mR­NA vac­cine, which would cov­er al­most 95 per­cent of the coun­try’s pop­u­la­tion. Fi­nan­cial terms of the deal were not dis­closed but are con­tin­gent on the tim­ing of de­liv­ery and vol­ume of dos­es.

The deal is al­so sub­ject to the can­di­date’s reg­u­la­to­ry ap­proval. As re­quest­ed by Japan, de­liv­er­ies of the vac­cine will start in the first half of 2021.

Pfiz­er is work­ing with BioN­Tech on four vac­cine pro­grams, two of which have re­ceived Fast Track des­ig­na­tion from the FDA. Ear­li­er this week, the com­pa­nies an­nounced the start of en­roll­ment for a Phase II/III study for the can­di­date BNT162b2, putting them on track for reg­u­la­to­ry re­view as ear­ly as Oc­to­ber.

That’s not the can­di­date most an­a­lysts ex­pect­ed to pro­vide the foun­da­tion for Pfiz­er’s vac­cine pro­gram, as BNT162b1 ap­peared more ex­cit­ing when pre­lim­i­nary da­ta dropped on Ju­ly 1. But BNT162b2 demon­strat­ed a bet­ter tol­er­a­bil­i­ty pro­file in Phase I/II, which end­ed up be­ing the de­cid­ing fac­tor along with T cell re­sponse. — Max Gel­man

For a look at all End­points News coro­n­avirus sto­ries, check out our spe­cial news chan­nel.

So­cial im­age: Daniel O’Day, Bloomberg via Get­ty

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

FDA announced today that doctors and pharmacists can now prescribe Paxlovid to patients without a positive test for Covid-19.

CDER Director Patrizia Cavazzoni reissued Paxlovid’s authorization letter Wednesday, saying it has revised the authorization to “no longer require positive results of direct SARS-CoV-2 viral testing.” The EUA now requires instead that adults and kids 12 years of age and older have a “current diagnosis of mild-to-moderate COVID-19.”

Sanofi expects its RSV antibody jointly developed with AstraZeneca will be available next season, executive VP of vaccines Thomas Triomphe announced on the company’s quarterly call.

Beyfortus, also known as nirsevimab, was approved in the EU back in November and is currently under FDA review with an expected decision coming in the third quarter of this year. The news comes as the FDA plans to hold advisory committee meetings over the next couple months to review RSV vaccines from Pfizer and GSK.