Ver­tex has been charm­ing an­a­lysts for years now with its dom­i­nance of the cys­tic fi­bro­sis are­na; the reign­ing champ that has brushed aside a long line­up of ban­tamweight biotechs that could nev­er quite land a sin­gle, sol­id blow. And they did it again Wednes­day evening with a look at Q4 num­bers that made it clear they would con­tin­ue to per­form ad­mirably through the year — pan­dem­ic or no pan­dem­ic.

This year, though, we’ll find out if Ab­b­Vie AB­BV has the po­ten­tial to step in­to the ring with a ri­val drug that they be­lieve can chal­lenge the champ in a block­buster show­down.

Or if it’s just an­oth­er vic­tim of Ver­tex.

First, let’s look at the num­bers.

Ver­tex VRTX beat con­sen­sus, an es­sen­tial step in the un­end­ing Wall Street game of beat-the-num­ber in your quar­ter­ly re­port. The com­pa­ny’s rev­enue hit $2.073 bil­lion, with Trikaf­ta sales slam­ming it right at $1.7 bil­lion. That puts Ver­tex on track to hit an­nu­al 2022 rev­enue goals of $8.4 bil­lion to $8.6 bil­lion — megablock­buster num­bers. And this is one big biotech that has al­ways prid­ed it­self on ef­fec­tive­ly gam­ing con­sen­sus, so look for more beats ahead in 2022. (They were 4 for 4 in beat­ing quar­ter­ly con­sen­sus for 2021.)

Strengths, though, of­ten mir­ror threats. And in Ver­tex’s case, crit­ics ob­serve, they’ve al­ways had way too many bil­lion-dol­lar CF eggs in its rev­enue bas­ket. Hence the line­up of home run swings the com­pa­ny is tak­ing in its R&D group in search of out-of-park hits to add to the CF fran­chise.

A not-so-fun­ny thing hap­pened to TG Ther­a­peu­tics on its way to the ac­com­mo­da­tion re­view for its lead drug. The CEO re­vealed at an in­vest­ment con­fer­ence to­day that the FDA has slapped a hold over a seg­ment of the R&D work it's do­ing on the drug — a piece of the clin­i­cal plan that spurred some sec­ond looks af­ter the haz­ard ra­tio made the drug look more dan­ger­ous than the com­para­tor.

It was all spelled out in a fresh SEC fil­ing to­day, not­ing that dur­ing a fire­side chat at the B. Ri­ley Se­cu­ri­ties’ 2022 Vir­tu­al On­col­o­gy In­vestor Con­fer­ence, CEO Michael Weiss star­tled in­vestors with the news that the FDA dropped a “par­tial clin­i­cal hold on se­lect stud­ies of U2 and its com­po­nents for chron­ic lym­pho­cyt­ic leukemia and non-Hodgk­in's lym­phoma.” The hold in­volves the U2 ther­a­py, a com­bi­na­tion of an an­ti-CD20 mon­o­clon­al an­ti­body and UKONIQ (um­bral­is­ib), their PI3K-delta and CK1-ep­silon in­hibitor com­pared to the con­trol arm of obin­u­tuzum­ab plus chlo­ram­bu­cil.

The com­pa­ny ex­plained that the haz­ard ra­tio from the UNI­TY-CLL study came in at 1.04 — af­ter the Covid deaths were sub­tract­ed from the mix.

In the state­ment, the biotech TGTX notes:

No new pa­tients can be en­rolled and pa­tients who are ben­e­fit­ting from the drug may con­tin­ue on ther­a­py.

That’s not what in­vestors ex­pect­ed to hear, ev­i­dent­ly, and the sub­se­quent stam­pede wiped out 40% of the biotech’s mar­ket val­u­a­tion.

For­mer FDA com­mis­sion­er and cur­rent Pfiz­er board mem­ber Scott Got­tlieb went on the of­fen­sive against CMS this morn­ing — cit­ing the agen­cy's "flawed de­ci­sion mak­ing" and how the agen­cy's de­ci­sion on Aduhelm is putting not just Alzheimer's drug re­search in lim­bo but po­ten­tial­ly set­ting a neg­a­tive prece­dent for ac­cel­er­at­ed ap­provals.

Got­tlieb, who was in charge of the fed­er­al agency from 2017-2019, talked with Bio­Cen­tu­ry's Steve Us­din on how the prece­dent that CMS is set­ting could im­pact ac­cel­er­at­ed ap­provals out­side of Alzheimer's — and even fur­ther, blur­ring the lines of au­thor­i­ty be­tween the FDA and CMS.

Got­tlieb, who spent some time in the ear­ly 2000s as a CMS se­nior ad­vi­sor, said that the cen­ter's de­ci­sion would cre­ate a lot of ob­sta­cles for pa­tients.

The for­mer FDA com­mis­sion­er added:

Got­tlieb fur­ther drove the point on ac­cel­er­at­ed ap­provals, and that CM­S' de­ci­sion put pret­ty much the en­tire field of Alzheimer's drug re­search in lim­bo. He said that CMS is "now us­ing the is­sue of whether or not a drug is ap­proved un­der reg­u­lar ap­proval ver­sus ac­cel­er­at­ed ap­proval as a ba­sis po­ten­tial­ly go­ing for­ward for deny­ing cov­er­age to drugs."

CDC di­rec­tor Rochelle Walen­sky took to Twit­ter last week to launch a first-ever "Di­rec­tor De­brief" se­ries, speak­ing di­rect­ly to fol­low­ers on the chan­nel. She in­tro­duced the videos with a look back at the past year since she joined, not­ing “the many chal­lenges faced in the past year” and promis­ing in 2022 “to use sci­ence and trans­paren­cy” to im­prove pub­lic health.

As the CDC ad­justs its com­mu­ni­ca­tions style — hold­ing so­lo press brief­in­gs re­cent­ly for the first time since Walen­sky joined a year ago as well as that video se­ries de­but on Twit­ter — the big­ger ques­tion is, can bet­ter com­mu­ni­ca­tions re­build pub­lic con­fi­dence in the agency?

The new com­mu­ni­ca­tions come amid an on­go­ing prob­lem for the CDC — plum­met­ing pub­lic trust. At the be­gin­ning of the pan­dem­ic in April 2020, for in­stance, Pew Re­searchers found that an over­whelm­ing ma­jor­i­ty, 79% of US adults, viewed the CDC fa­vor­ably. Re­pub­li­cans and in­de­pen­dents lean­ing Re­pub­li­can led the way at 84% fa­vor­able, fol­lowed by De­moc­rats and De­mo­c­ra­t­ic lean­ers at 77%.

Then a mid-pan­dem­ic Pew query in March 2021 found that had dropped to 62% of US adults over­all who thought pub­lic health of­fi­cials in­clud­ing those at the CDC were do­ing an ex­cel­lent or good job. As the poll­sters not­ed then, “the rat­ing is down 5 points since No­vem­ber and much low­er than the 79% … dur­ing the ear­ly stages of the out­break in March 2020.”

While Pew hasn’t asked the ques­tion again yet this year, oth­er polls are show­ing big drops. A re­cent NBC News poll found that on­ly 44% of the US adults it sur­veyed said they trust­ed the CDC when it comes to Covid-19, while an al­most equal 43% said they didn’t trust the CDC on the virus.

With law­suits pil­ing up al­leg­ing its talc-based prod­ucts caused can­cer, J&J con­tro­ver­sial­ly spun its re­lat­ed li­a­bil­i­ties in­to a sep­a­rate com­pa­ny and filed for bank­rupt­cy back in Oc­to­ber. Now a com­mit­tee rep­re­sent­ing the talc claimants is say­ing not so fast — and sev­en bank­rupt­cy law pro­fes­sors are join­ing the cho­rus.

A group of pro­fes­sors from uni­ver­si­ties across the coun­try is look­ing to sub­mit an am­i­ci cu­ri­ae, or “friend of the court,” brief in sup­port of a mo­tion by the talc claimants’ com­mit­tee to dis­miss J&J’s Chap­ter 11 case, ac­cord­ing to court doc­u­ments filed on Tues­day.

In their brief, the pro­fes­sors called J&J’s move a “di­rect at­tack on the fun­da­men­tal in­tegri­ty of the Chap­ter 11 sys­tem,” that would “de­prive in­no­cent talc vic­tims of their day in court.” A tri­al on the com­mit­tee’s mo­tion to dis­miss is ex­pect­ed to be­gin in just a few weeks, on Feb. 14.

The case stems back to law­suits — 38,000 of them — claim­ing J&J’s wide­ly-used ba­by pow­der and oth­er talc prod­ucts con­tained as­bestos and caused mesothe­lioma and ovar­i­an can­cer. J&J said back in Oc­to­ber that it had racked up near­ly $1 bil­lion in de­fense costs, and about $3.5 bil­lion in pay­ments for set­tle­ments and ver­dicts.

Though that’s just a drop in the buck­et for J&J, which has a mar­ket cap of more than $450 bil­lion, the com­pa­ny ar­gued that the costs were un­ten­able and that a Chap­ter 11 was nec­es­sary “to ap­pro­pri­ate­ly as­sess, re­solve, and ad­min­is­ter these claims in an ef­fi­cient and eq­ui­table man­ner.”

For over 30 years, can­cer re­searchers have known some­thing rather ex­tra­or­di­nary, giv­en how hard it nor­mal­ly is to treat ad­vanced tu­mors.

If you just ex­tract the T cells float­ing in­side cer­tain pa­tients' tu­mors— a 10 to 30 gram slice will do —  ex­pand those cells in a lab, and re­in­fuse them back in­to the pa­tient, there’s a high like­li­hood those tu­mors will soon shrink. The NCI’s proof-of-prin­ci­ple ex­per­i­ment showed a 60% re­sponse rate in metasta­t­ic melanoma in 1988 — more than two decades be­fore oth­er im­munother­a­pies would be­gin to change can­cer care.

The tech­nique has al­so yield­ed ear­ly signs of ef­fi­ca­cy in lung can­cer, cer­vi­cal can­cer, col­orec­tal can­cer and breast can­cer, among oth­er tu­mor types.

Some pa­tients “have a mirac­u­lous re­sponse,” said Shana Kel­ley, a pro­fes­sor of chem­istry at North­west­ern Uni­ver­si­ty. “They can be cured. But it’s a very small per­cent­age.”

And yet tu­mor-in­fil­trat­ing lym­pho­cyte ther­a­py (TIL for short), as the pro­ce­dure is known, has still not been ap­proved for any type of can­cer. The prob­lem is es­sen­tial­ly two-fold, though both parts are con­nect­ed: First, the still-slow and cum­ber­some process re­quired to get T cells to grow out­side the body. And, per­haps more im­por­tant­ly, the vague­ly me­dieval na­ture of the en­tire op­er­a­tion.

TILs op­er­ate on a ba­sic in­tu­ition about can­cer bi­ol­o­gy: that most pa­tients' T cells al­ready have some T cells that have fig­ured out how to pen­e­trate a tu­mor’s myr­i­ad de­fens­es. They just need more of them.

The FDA on Wednes­day re­leased a trio of new guid­ance doc­u­ments un­der its Drug Com­pe­ti­tion Ac­tion plan to help the gener­ic drug in­dus­try with a more ef­fi­cient and trans­par­ent gener­ic drug re­view process.

One of the two fi­nal guid­ances re­leased deals with how the agency is­sues and us­es in­for­ma­tion re­quests (IRs) and dis­ci­pline re­view let­ters (DRLs) dur­ing the as­sess­ment of an orig­i­nal gener­ic drug ap­pli­ca­tion, al­so known as an ab­bre­vi­at­ed new drug ap­pli­ca­tion or AN­DA.

This guid­ance, which fi­nal­izes a draft from 2017, al­so ex­plains the tim­ing of an IR or a DRL and the ef­fect each will have on the as­sess­ment clock for a giv­en cy­cle. "Mi­nor changes were made from the draft to the fi­nal guid­ance, pri­mar­i­ly to re­flect cur­rent ter­mi­nol­o­gy," the FDA said.

The oth­er fi­nal guid­ance, build­ing on a draft from 2018, high­lights com­mon, re­cur­ring de­fi­cien­cies in AN­DAs that may lead to oth­er ap­proval de­lays.

The FDA and gener­ic in­dus­try have long bat­tled mul­ti­ple re­view cy­cles that can take years of back-and-forth and keep com­pe­ti­tion at bay, even as the over­whelm­ing ma­jor­i­ty of new drug ap­pli­ca­tions are ap­proved on the first try.

"Mul­ti­ple re­view cy­cles are high­ly in­ef­fi­cient, re­quire sig­nif­i­cant re­sources from ap­pli­cants and FDA, and de­lay pa­tient ac­cess to more af­ford­able gener­ic drugs," the FDA said. "By pro­vid­ing rec­om­men­da­tions to ap­pli­cants on how to avoid these com­mon de­fi­cien­cies, this guid­ance will help ap­pli­cants sub­mit high-qual­i­ty, com­plete ap­pli­ca­tions the agency can ap­prove in the first re­view cy­cle."

Ever since HIV first emerged decades ago, progress made to­wards treat­ing the dis­ease com­plete­ly has been slow. Al­though the in­fec­tion has gone from a death sen­tence to a chron­ic dis­ease, kept at bay with a con­stant in­take of an­ti-retro­vi­ral drugs, it re­mains in­cur­able.

Now, re­searchers at Fred Hutch say that Keytru­da, Mer­ck­'s an­ti-PD-1 can­cer megablock­buster, might be able to dis­place the virus from hu­man im­mune cells — which would be a game chang­er for treat­ment. The re­searchers claim that Keytru­da, which works by block­ing a re­cep­tor (PD-1) that tu­mors hi­jack to turn off T cells, can re­verse HIV's abil­i­ty to hide in cells and evade the im­mune sys­tem.

The study, pub­lished yes­ter­day in Sci­ence Trans­la­tion­al Med­i­cine, en­rolled 32 peo­ple with both can­cer and HIV, with the par­tic­i­pants al­so be­ing treat­ed with an­tivi­ral med­i­cines for HIV. Each pa­tient was giv­en 200 mg of Keytru­da every three weeks for up to 105 weeks, in some cas­es.

What makes HIV so hard to cure — de­spite a mo­men­tous re­search ef­fort over the past 4+ decades — is that the virus can lie dor­mant and hide from the im­mune sys­tem, par­tic­u­lar­ly in a group of T cells called CD4 lym­pho­cytes. This is known as the HIV reser­voir. While HIV is la­tent in the reser­voir, it does­n't repli­cate, but it can wake up, caus­ing vi­ral load to in­crease. Get­ting the virus out of those reser­voirs is para­mount to cur­ing HIV.

LifeS­can’s One­Touch blood glu­cose mon­i­tor­ing brand, once part of the John­son & John­son port­fo­lio, has a well-rec­og­nized 40-year his­to­ry in both health­care and ad­ver­tis­ing.

In the ear­ly 2000s, One­Touch TV ads with Amer­i­can blues singer-song­writer and leg­end BB King brought di­a­betes blood sug­ar test­ing to the main­stream. The King of Blues played his gui­tar while he talked about his type 2 di­a­betes in a se­ries of TV com­mer­cials in 2000, de­liv­er­ing clas­sic lines like “Di­a­betes is no joke” in his deep bari­tone.

Now LifeS­can is rolling out an up­dat­ed tech-en­abled take on di­a­betes man­age­ment along with a new spokesper­son – re­tired Na­tion­al Foot­ball League play­er and sports com­men­ta­tor Mike Golic who al­so has type 2 di­a­betes. Mov­ing be­yond just mak­ing blood sug­ar mon­i­tor­ing de­vices, LifeS­can is fo­cus­ing on a suite of dig­i­tal pro­grams and sup­port called One­Touch So­lu­tions.

LifeS­can is part­ner­ing with Noom, Fit­bit, Ce­celia Health and Well­doc for dig­i­tal ac­cess to healthy eat­ing, fit­ness, coach­ing and mul­ti-con­di­tion chron­ic dis­ease man­age­ment so type 2 pa­tients can pick and choose the sup­port ser­vices.

“It isn’t about prod­ucts and fea­tures any­more. It’s about that holis­tic so­lu­tion and sur­round­ing peo­ple with di­a­betes with more ca­pa­bil­i­ties and sup­port,” Lisa Rose, LifeS­can’s chief mar­ket­ing of­fi­cer, said.

Golic’s team mind­set, and his per­son­al type 2 man­age­ment over the past 17 years, made him an ide­al spokesper­son to de­liv­er the One­Touch mes­sage to help each cus­tomer build a per­son­al play­book with a “team” of sup­port tools.

Back in late Sep­tem­ber, the FDA re­leased a long-await­ed guid­ance on how the in­dus­try might use elec­tron­ic health records (EHRs) or med­ical claims da­ta in clin­i­cal stud­ies to sup­port a reg­u­la­to­ry de­ci­sion for ef­fec­tive­ness or safe­ty.

The draft guid­ance of­fered some light from FDA on which strate­gies might help a spon­sor get a new ap­proval across the fin­ish line or help with an sN­DA or sBLA. A to­tal of 57 com­ments were filed on the draft, with some com­pa­nies like Re­gen­eron, Janssen, and Am­gen, as well as in­dus­try groups like PhRMA and the RWE Al­liance, seek­ing ad­di­tion­al clar­i­ty and of­fer­ing sug­ges­tions.

Am­gen, for in­stance, called on the FDA to pro­vide more spe­cif­ic guid­ance "to en­able da­ta providers to gen­er­ate con­sis­tent as­sess­ment re­ports for da­ta qual­i­ty that will meet the Agency’s needs as part of a spon­sor’s reg­u­la­to­ry sub­mis­sions."

The com­pa­ny al­so said the draft guid­ance could "more clear­ly out­line ways to seek agree­ment with the Agency on key vari­ables that re­quire val­i­da­tion."

While not­ing some cir­cum­stances when val­i­da­tion may not be al­ways need­ed or use­ful ("e.g., when val­i­da­tion stud­ies have been pre­vi­ous­ly con­duct­ed in the same da­ta source"), Am­gen sug­gests vari­ables of im­por­tance for val­i­da­tion "could be dis­cussed and agreed to with FDA be­fore the study be­gins as part of an ear­ly in­ter­ac­tion with the FDA. This process could be out­lined in the guid­ance."

Re­gen­eron called on FDA to rec­og­nize that this is a "dy­nam­ic top­ic" and to pro­vide ad­di­tion­al de­tails on the sub­mis­sion of the pro­to­col or sta­tis­ti­cal analy­sis plan, the types of in­ter­ac­tions that spon­sors should ex­pect (e.g. meet­ing/writ­ten feed­back), time­lines for such feed­back, etc.

In 2021, it seemed like every two weeks, CD­MO gi­ant Catal­ent would re­lease some sort of im­por­tant news. If there was any ques­tion of whether the com­pa­ny could keep up the pace this year, those con­cerns were quelled al­most im­me­di­ate­ly, when its col­or­ful, out­spo­ken, long­time CEO John Chimin­s­ki an­nounced that he would step down lat­er this year af­ter 12 years.

And in four weeks, the com­pa­ny has an­nounced four deals. The lat­est: Catal­ent will pump $10 mil­lion in­to ex­pan­sions at its Malvern, PA and Dart­ford, UK sites to ex­pand the large-scale iso­la­tor units, in an ef­fort to im­prove con­tain­ment ca­pa­bil­i­ties for the mi­croniza­tion of high­ly-po­tent drugs.

Mi­croniza­tion is the process of re­duc­ing the di­am­e­ter of a sol­id ma­te­r­i­al’s par­ti­cles to al­low ac­tive phar­ma­ceu­ti­cal in­gre­di­ents to be­come sol­u­ble. If a drug is tak­en oral­ly or top­i­cal­ly, sol­u­bil­i­ty plays a key role in its ef­fec­tive­ness. All APIs need to be mi­cronized to in­crease strength, and the process is fa­vored be­cause of the sim­ple process need­ed to scale up and the cost ef­fec­tive­ness, Catal­ent said.

“These ex­pan­sions pro­vide the in­creased ca­pac­i­ty need­ed to meet cur­rent and fu­ture de­mand for high po­tent, high val­ue mi­croniza­tion,” said James Wal­ter, the VP of op­er­a­tions, oral and spe­cial­ty de­liv­ery, in a press re­lease.

A new hard-wall iso­la­tor sys­tem at each site will al­so en­able com­mer­cial scale jet milling, which is a pre­ferred method for con­trol­ling the par­ti­cle size and im­prov­ing the bioavail­abil­i­ty for poor­ly sol­u­ble com­pounds, which in­cludes high po­ten­cy APIs. A pow­der is loaded in­to a feed fun­nel and in­ject­ed in­to the main cham­ber of a mi­croniz­er, and then com­pressed gas is blown in through jet noz­zles, prod­uct mar­ket­ing man­ag­er Julie Do­boszczak said in an email. That forces the pow­der par­ti­cles to col­lide in­to each oth­er and break apart.