Con­gres­sion­al watch­dog ad­vis­es HHS to im­ple­ment 'post-mar­ket­ing' in­cen­tives to ad­dress dwin­dling an­tibi­ot­ic de­vel­op­ment ef­forts

With the Covid-19 cri­sis ex­pect­ed to shore up an­tibi­ot­ic use with op­por­tunis­tic sec­ondary bac­te­r­i­al in­fec­tions — and po­ten­tial­ly ex­ac­er­bate the rate an­tibi­ot­ic re­sis­tance — a con­gres­sion­al watch­dog has put to­geth­er a list of rec­om­men­da­tions to sort out the chal­lenges af­fect­ing an­tibi­ot­ic stew­ard­ship, track rates of drug re­sis­tance, and fix the ‘bro­ken’ mar­ket for an­tibi­otics.

While bac­te­r­i­al pathogens mu­tate and grow re­sis­tant to the ex­ist­ing crop of an­tibi­otics, dri­ven by un­bri­dled use in hu­mans and live­stock — the in­dus­try play­ers con­tribut­ing to the ar­se­nal of an­timi­cro­bials are fast dwin­dling, and the pipeline for new an­tibi­otics is em­bar­rass­ing­ly sparse, the WHO has warned.

The US Gov­ern­ment Ac­count­abil­i­ty Of­fice, on Wednes­day, is­sued a re­port en­com­pass­ing da­ta from doc­u­ments and in­ter­views with agency of­fi­cials and ex­perts, find­ing that there are var­i­ous chal­lenges in im­ple­ment­ing ap­pro­pri­ate an­tibi­ot­ic use in the Unit­ed States, for in­stance, fed­er­al re­quire­ments for an­tibi­ot­ic stew­ard­ship pro­grams ap­ply to on­ly cer­tain health care fa­cil­i­ties, and in­cen­tives for doc­tors to adopt an­tibi­ot­ic stew­ard­ship ac­tiv­i­ties are op­tion­al.

Source: GAO, 2020

Click on the im­age to see the full-sized ver­sion

The re­port rec­og­nized that al­though there is a raft of in­cen­tives in place to push drug­mak­ers to de­vel­op an­tibi­otics, such as fund­ing sup­port through the Bio­med­ical Ad­vanced Re­search and De­vel­op­ment Au­thor­i­ty (BAR­DA) and reg­u­la­to­ry re­forms such as the Lim­it­ed Pop­u­la­tion Path­way for An­tibac­te­r­i­al and An­ti­fun­gal Drugs (LPAD) —  there is a des­per­ate need for the pas­sage of “pull in­cen­tives,” or pol­i­cy mea­sures to in­crease the val­ue of a mar­ket­ed an­tibi­ot­ic by re­ward­ing drug­mak­ers on­ly af­ter their an­tibi­ot­ic is ap­proved.

Ex­ist­ing in­cen­tives, “while well-in­ten­tioned…ap­pear to have been in­suf­fi­cient, as they fo­cused ex­clu­sive­ly on bol­ster­ing the de­vel­op­ment pipeline with­out re­mov­ing the block­age cre­at­ed by is­sues with pay­ment,” CMS ad­min­is­tra­tor Seema Ver­ma con­ced­ed last Au­gust.

There has been a slew of bank­rupt­cies in the an­tibi­ot­ic sec­tor, as com­pa­nies see their val­ue go up in smoke as fee­ble sales frus­trat­ed growth. The long, ar­du­ous and ex­pen­sive path to an­tibi­ot­ic ap­proval — com­pli­cat­ed by is­sues of clin­i­cal tri­al en­roll­ment (there are no rapid di­ag­nos­tic tests to iden­ti­fy in­fec­tions,  and it is hard to re­cruit pa­tients in clin­i­cal tri­als to test an­tibi­otics that tar­get re­sis­tant bac­te­ria) of­fers lit­tle fi­nan­cial gain as treat­ments are typ­i­cal­ly priced cheap­ly. The me­di­an an­nu­al sales for brand name an­tibi­otics be­tween 2011 and 2015 ranged from $24 mil­lion to $75 mil­lion, where­as an­nu­al sales for most new, brand-name on­col­o­gy drugs were more than $500 mil­lion dur­ing the same pe­ri­od, the GAO re­port said.

For one of the biggest threats to glob­al health, the li­on’s share of an­tibi­ot­ic de­vel­op­ment is now tak­ing place in a hand­ful of labs of small bio­phar­ma com­pa­nies as a ma­jor­i­ty of their larg­er coun­ter­parts fo­cus on more lu­cra­tive en­deav­ors such as on­col­o­gy. Big Phar­ma has large­ly re­treat­ed from an­tibi­otics, and on­ly a hand­ful re­main in the space — in­clud­ing Mer­ck, Roche and GSK — down from more than 20 in the 1980s.

For­mer FDA com­mis­sion­er Scott Got­tlieb, in 2018, sug­gest­ed a “li­cens­ing mod­el” in which acute care in­sti­tu­tions that pre­scribe an­timi­cro­bial med­i­cines pay a fixed li­cens­ing fee for ac­cess to these drugs, grant­i­ng them the right to use a cer­tain num­ber of an­nu­al dos­es. Last year, the CMS un­veiled a pro­pos­al to re­struc­ture the pay­ment ap­pa­ra­tus to res­cue ex­ist­ing an­tibi­ot­ic man­u­fac­tur­ers, by clas­si­fy­ing drug re­sis­tance in a way that would com­pel high­er pay­ments to hos­pi­tals treat­ing pa­tients with an­timi­cro­bial re­sis­tance, and craft­ing a path­way for doc­tors to pre­scribe ap­pro­pri­ate new an­tibi­otics with­out dis­rupt­ing hos­pi­tal bud­gets. Un­der the cur­rent sys­tem, hos­pi­tals bun­dle to­geth­er the costs of all the ser­vices for a giv­en di­ag­no­sis, which tends to in­cen­tivize hos­pi­tals to pre­scribe cheap­er, gener­ic an­tibi­otics that are not en­gi­neered to tack­le drug-re­sis­tant in­fec­tions.

The GAO made 8 rec­om­men­da­tions fix the myr­i­ad of prob­lems, in­clud­ing that the CDC should de­vel­op a plan for con­sol­i­dat­ed re­ports of an­tibi­ot­ic re­sis­tance in pri­or­i­ty pathogens at reg­u­lar in­ter­vals; the HHS should iden­ti­fy lead­er­ship and clar­i­fy roles and re­spon­si­bil­i­ties among HHS agen­cies to as­sess the clin­i­cal out­comes of di­ag­nos­tic test­ing for iden­ti­fy­ing an­tibi­ot­ic-re­sis­tant bac­te­ria; and im­por­tant­ly that the HHS should come up with a strate­gic frame­work to fur­ther in­cen­tivize an­tibi­otics for drug-re­sis­tant in­fec­tions, in­clud­ing through the use of post­mar­ket fi­nan­cial in­cen­tives.

Each rec­om­men­da­tion apart from the post­mar­ket fi­nan­cial in­cen­tives was ac­cept­ed by the var­i­ous agen­cies. “HHS not­ed that, while it agrees that ad­di­tion­al in­cen­tives are need­ed to ad­dress the lim­it­ed pipeline for nov­el and in­no­v­a­tive treat­ments to com­bat an­tibi­ot­ic re­sis­tance, it is still con­duct­ing analy­ses to un­der­stand whether post­mar­ket in­cen­tives should be in­clud­ed as a com­po­nent of its forth­com­ing strate­gic frame­work to fur­ther in­cen­tivize the de­vel­op­ment of new treat­ments. How­ev­er, HHS did not spec­i­fy when its frame­work would be re­leased,” the GAO re­port said.

The au­thors, how­ev­er, stood by their call: “We be­lieve our rec­om­men­da­tion is still war­rant­ed.”

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

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Matt Gline (L) and Vivek Ramaswamy

Scoop: Vivek Ra­maswamy is hand­ing the CEO job to a top lieu­tenant at Roivant — but he’s not ex­act­ly leav­ing the biotech scene

Over the past 7 years since founding Roivant, Vivek Ramaswamy has been a constant blur of biotech building motion.

He launched his first biotech with an Alzheimer’s drug he picked up cheap, and watched the experiment implode in one of the highest profile pivotal disasters seen in the last decade. But it didn’t slow the 30-something exec down; if anything, he hit the accelerator. Ramaswamy blazed global paths and went on to raise billions to spur the creation of a large lineup of little Vants promising big things at a fast pace. He sold off a section of the Vant brigade to Sumitomo Dainippon for $3 billion. And more recently the relentless dealmaker has been building a computational discovery arm to add an AI-driven approach to kicking up new programs and companies, supplementing the in-licensing drive while pursuing advances that have created more than 700 jobs at Roivant, with $2 billion in reserves.

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José Baselga, AstraZeneca cancer chief (Brent N. Clarke/FilmMagic via Getty Images)

As­traZeneca's Calquence nabs an­oth­er win against Im­bru­vi­ca, but Eli Lil­ly is on its heels

Three years after first launching Calquence as a second generation BTK inhibitor, AstraZeneca continues to tout new data to compete with J&J and AbbVie’s first generation blockbuster Imbruvica.

The British pharma announced on Monday that Calquence passed a head-to-head Phase III study against Imbruvica in chronic lymphocytic leukemia, proving non-inferior — i.e. just as good — as the older drug. Although AstraZeneca did not break down any of the numbers, they said the drug proved superior on safety, triggering fewer cases of atrial fibrillation, an irregular heartbeat that can lead to stroke or heart failure.

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Covid-19 roundup: Mod­er­na dou­bles down on Covid-19 with new boost­er tri­als; Aus­tralia plans do­mes­tic pro­duc­tion of As­traZeneca vac­cine amid dis­tri­b­u­tion lag

As Merck bows out of the global race to develop vaccines for Covid-19, Moderna is doubling down to make sure they can quell new variants that have recently emerged and quickly spread.

The Cambridge, MA-based biotech put out word on Monday that in vivo studies indicate their mRNA vaccine works well enough against two strains first detected in the UK and South Africa. But with a six-fold reduction in neutralizing titers observed against the latter strain, the company is launching a new study of a booster version to make sure it can do the job.

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Jean-Christophe-Hyvert, Lonza

Lon­za look­ing to build on 'd­if­fer­en­ti­at­ed ad­van­tage' in Covid-19, CD­MO mar­ket­place in 2021

It’s not new for Lonza, the Swiss CDMO nearing its quasquicentennial anniversary, to be in the upper echelon of the biotech manufacturing industry.

But 2020 — as it was for many CDMOs — was a special year even by Lonza’s standards. The company inked a deal to produce 1 billion worldwide doses of Moderna’s Covid-19 vaccine and tapped pharma vet Pierre-Alain Ruffieux to lead its operations, moves which have allowed Lonza to make a myriad of other deals that will continue to ramp up its global production capacity.

News brief­ing: Jef­frey Lei­den to chair Tmu­ni­ty board of di­rec­tors; Op­di­vo wins new ap­proval in ad­vanced RCC

Longtime Vertex CEO Jeffrey Leiden is taking on a new role.

Leiden has been appointed chairman of Tmunity’s board of directors, the company announced Monday. The move comes about a year and a half after Leiden announced he’d be stepping down from his position at Vertex.

Vertex saw immense growth under Leiden, leading the company from its exit out of hepatitis C, when cures were moving in, and into cystic fibrosis. The company’s cystic fibrosis triple combo therapy Trikafta is already its best-seller, reaching the distinction just six weeks after launch and recording the strongest first quarter of sales for any drug, per some estimates.

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When Albireo Pharma’s board $ALBO moved to bring in Ron Cooper as the CEO more than 5 years ago, the development-stage company went with an experienced commercial player who had a big-time position on his resume after running Bristol Myers’ commercial ops in Europe.

Now, after successfully navigating a pivotal study, putting them in a foot race with a rival toward an FDA OK, Cooper is getting a boost from regulators on the last drive back to an arena he understands completely.

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IPO track­er: 2021 gets start­ed with a flur­ry of new of­fer­ings

A global pandemic couldn’t slow down what turned out to be a record year for biotech IPOs. With the calendar turning toward 2021, the Endpoints News team is prepped to track each new filing this year, and the outcome. We’re off to another hot start at least.

Below, you’ll find the companies that have filed to go public, in addition to those that have already priced. Through the first two business weeks of January, there have already been 9 biotechs that have filed or priced, and the number is only expected to grow. We’ll keep the tracker updated as it does.