Es­ti­mat­ing a US price tag of $5K per course, remde­sivir is set to make bil­lions for Gilead, says key an­a­lyst

Da­ta on remde­sivir — the first drug shown to ben­e­fit Covid-19 pa­tients in a ran­dom­ized, con­trolled tri­al set­ting — may be murky, but its mak­er Gilead could reap bil­lions from the sales of the failed Ebo­la ther­a­py, ac­cord­ing to an es­ti­mate by a promi­nent Wall Street an­a­lyst. How­ev­er, the fore­cast, which is based on a $5,000-per-course US price tag, trig­gered the ire of one top drug price ex­pert.

Ge­of­frey Porges

Gilead has been ret­i­cent about its pric­ing plans, with com­pa­ny chief Dan O’Day em­pha­siz­ing the need for the com­pa­ny to be re­spon­si­ble. “I don’t think there is a prece­dent for this,” he said in re­sponse to the ques­tion posed by SVB Leerink an­a­lyst Ge­of­frey Porges in a post-earn­ings con­fer­ence call last month. “There is no rule book out there, oth­er than that we need to be very thought­ful about how we can make sure we pro­vide ac­cess to our med­i­cine to pa­tients around the globe and do that in a sus­tain­able way for the com­pa­ny.”

But on Wednes­day, Porges said he ex­pect­ed the drug to car­ry a list price of $5000 per course in the Unit­ed States, above the cost-ef­fec­tive es­ti­mate of $4,500 gen­er­at­ed by ICER, an in­creas­ing­ly in­flu­en­tial watch­dog that typ­i­cal­ly fa­vors a con­ser­v­a­tive ap­proach to pric­ing based on an in­ter­ven­tion’s ben­e­fit be­yond the stan­dard-of-care.

Al­though Remde­sivir is the on­ly ther­a­py so far to show a sta­tis­ti­cal­ly sig­nif­i­cant im­pact in help­ing hos­pi­tal­ized Covid-19 pa­tients with mod­er­ate-to-se­vere dis­ease re­cov­er faster (by four days) in a ran­dom­ized, place­bo-con­trolled study — the gold-stan­dard for ben­e­fit-risk cal­cu­la­tions — it is by no means a sil­ver bul­let. The drug, which thwarts an en­zyme the virus re­lies on to repli­cate, did not re­duce the rate of mor­tal­i­ty by a sta­tis­ti­cal­ly sig­nif­i­cant ex­tent in the tri­al.

ICER broke its usu­al prac­tices in ear­ly May to con­duct its own analy­sis based on ‘raw and im­ma­ture da­ta’ to come up with two dif­fer­ent ways to rea­son­ably price for the drug. The first, the ‘cost re­cov­ery’ mod­el in which the man­u­fac­tur­er prices the ther­a­py on the ba­sis of the min­i­mum costs of pro­duc­tion, chalked up a price of $10 for a 10-day course. (Al­though da­ta from a Gilead tri­al sug­gest a 5-day reg­i­men of the drug is as ef­fec­tive as the 10-day course).

But un­der the tra­di­tion­al cost-ef­fec­tive­ness mod­el, which looks at in­cre­men­tal health ben­e­fits and costs with­in the health sys­tem, the com­pa­ny would be jus­ti­fied to sell the same reg­i­men for $4,500, ICER sug­gest­ed in a draft re­port.

Michael Car­rie Rut­gers Uni­ver­si­ty

Michael Car­ri­er, a Rut­gers Uni­ver­si­ty law school pro­fes­sor who spe­cial­izes in in­tel­lec­tu­al prop­er­ty, in a pre­vi­ous in­ter­view with End­points News not­ed that there isn’t any sim­ple for­mu­la to cal­cu­late the ide­al price of a ther­a­py. “Just psy­cho­log­i­cal­ly, a cost or price be­low $1,000 seems to be more af­ford­able. I don’t think it’s go­ing to be $10. I don’t think it’ll be close to $4500.”

“Wall Street ex­pect­ing $GILD to ex­tract max­i­mum rev­enue ex­ceed­ing treat­ment val­ue.  No one should be sur­prised by this,” said Pe­ter Bach, the di­rec­tor of Memo­r­i­al Sloan Ket­ter­ing’s Cen­ter for health pol­i­cy and out­comes, in re­sponse to Porges’ es­ti­mate of $5,000-per-course on Twit­ter.

Gilead rose to promi­nence by vault­ing HIV to the ranks of a chron­ic dis­ease and as the pur­vey­or of im­pos­si­bly high-priced, but fan­tas­ti­cal­ly ef­fec­tive, he­pati­tis C drugs. Orig­i­nal­ly priced at $1000 per hep C pill, the US drug­mak­er drew the wrath of law­mak­ers and pol­i­cy­mak­ers at home and abroad, and as a re­sult of in­tense scruti­ny and emerg­ing com­pe­ti­tion, prices were re­vised down­wards.

Porges, on Wednes­day, es­ti­mat­ed the drug will be priced at $4000 per course in Eu­rope and $2000 for the same reg­i­men in oth­er mar­kets. Over­all, the fore­cast glob­al remde­sivir sales is $1.9 bil­lion by the end of this year, jump­ing to $6.7 bil­lion in 2021 (bol­stered by gov­ern­ment stock­pil­ing) and then in a range of $5.8 to $6.9 bil­lion in lat­er years.

Pe­ter Bach

“This fore­cast has more un­cer­tain­ty than any that we have pub­lished in the last 15 years, but it re­flects our view that remde­sivir works, it saves med­ical and so­ci­etal costs by short­en­ing dis­ease du­ra­tion and re­duc­ing sever­i­ty, and we be­lieve that Gilead will be per­mit­ted to cap­ture re­duced but still re­al prof­itabil­i­ty from the prod­uct,” he wrote. “We al­so be­lieve that SARS-nCoV2 (the virus be­hind Covid-19) is not go­ing away, or be­ing elim­i­nat­ed by vac­ci­na­tion (we do fore­cast grad­ual adop­tion of vac­ci­na­tion, but in our view that is un­like­ly to stop gov­ern­ment stock­pil­ing of remde­sivir).”

Len Yaffe, a for­mer sell-side med­ical an­a­lyst who now works with a health­care hedge fund called Stoc*Doc Part­ners, said he does not see the US da­ta on hos­pi­tal­ized/in ICU/on ven­ti­la­tor pa­tients sup­port Porges’ rev­enue pro­jec­tions.

“I ex­pect the num­ber of dai­ly new cas­es to drop sig­nif­i­cant­ly by Sep­tem­ber from the cur­rent run rate of 20,000 to un­der 10,000 — by the late fall, there should be drugs ef­fec­tive in ear­li­er treat­ment that would min­i­mize the mod­er­ate to se­vere­ly ill pa­tient group,” he told End­points. “So, if I am wrong, and there is a sig­nif­i­cant sec­ond wave ( I ex­pect a mi­nor one) this win­ter, then he (Porges) could be cor­rect…but I think he needs to base his case on the pos­si­ble in­tro­duc­tion of oth­er phar­ma­ceu­ti­cals, a new case pro­jec­tion (not just that the virus is “not go­ing away”), and not on grad­ual adop­tion of vac­ci­na­tion.”

Porges’ fore­cast is cer­tain­ly gen­er­ous, but the da­ta on the drug are less than stel­lar. On­ly days ago, Gilead un­veiled da­ta from an open-la­bel late-stage study that gen­er­at­ed more ques­tions than an­swers on the mag­ni­tude of remde­sivir’s ben­e­fit in the treat­ment of Covid-19. In this tri­al, pa­tients clas­si­fied as hav­ing mod­er­ate dis­ease were 65% more like­ly to show “clin­i­cal im­prove­ment” on a five-day reg­i­men com­pared to those giv­en stan­dard-of-care — but not those on the 10-day course.

The di­choto­my per­plexed Baird an­a­lyst Bri­an Sko­r­ney. The da­ta “con­tin­ue to in­di­cate a very mar­gin­al clin­i­cal ben­e­fit, while re­in­forc­ing that a ben­e­fit is like­ly more than ran­dom noise,” he wrote in a note. “We con­tin­ue to be­lieve that both the com­mer­cial op­por­tu­ni­ty for Gilead and the macro ben­e­fit of remde­sivir to so­ci­ety, at large, is very lim­it­ed.”

Gilead, mean­while, has al­ready do­nat­ed 200,000 course sup­ply of remde­sivir to gov­ern­ments, in­vest­ed $50 mil­lion in de­vel­op­ing the drug, and ex­pects to spend an­oth­er $1 bil­lion as it ramps up fur­ther de­vel­op­ment and man­u­fac­tur­ing of remde­sivir. The com­pa­ny plans to dis­close its pric­ing plans in the com­ing weeks and kick off com­mer­cial sales in the sec­ond half of this year.

Stock­pil­ing could be­gin in late 2021, af­ter drug pro­duc­tion has been amped up, Porges said. “We as­sume that peak prof­itabil­i­ty (op­er­at­ing mar­gin) for remde­sivir is 19% in 2021, and then de­clines as more and more rev­enue comes from heav­i­ly dis­count­ed (80%+) gov­ern­ment stock­pil­ing pur­chas­es. As a re­sult of the much low­er prof­itabil­i­ty com­pared to Gilead’s core busi­ness, the in­cre­men­tal prof­it con­tri­bu­tion is rel­a­tive­ly small (+2% in 2020, +10% in 2021 and then +1-4% in lat­er years).”

In the Unit­ed States, days af­ter topline da­ta on the drug were an­nounced by the NIH, the FDA is­sued a quick emer­gency use au­tho­riza­tion (a tem­po­rary move to al­low ac­cess to the drug while its mak­er gath­ers more da­ta in or­der to pur­sue stan­dard ap­proval). In the Eu­ro­pean Union, the med­i­cines reg­u­la­tor has rec­om­mend­ed ex­pand­ing com­pas­sion­ate use of remde­sivir in se­vere Covid-19 pa­tients, while a rolling re­view of the drug is on­go­ing. In the UK, the Gilead has struck a deal with the gov­ern­ment to sup­ply the drug for cer­tain Covid-19 pa­tients.

So­cial im­age: Daniel O’Day, AP Im­ages

What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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President Biden and Pfizer CEO Albert Bourla (Patrick Semansky/AP Images)

Chaot­ic ad­comm sees Pfiz­er/BioN­Tech boost­ers re­ject­ed for gen­er­al pop­u­la­tion, but rec­om­mend­ed for old­er and high-risk pop­u­la­tions

With just days before President Joe Biden’s Covid-19 booster rollout is set to go into effect, an FDA advisory committee appeared on the verge of not recommending boosters for anyone in the US before a last-minute change of wording laid the groundwork for older adults to have access to a third dose.

The FDA’s adcomm on Vaccines and Related Biological Products (VRBPAC) roundly rejected Pfizer/BioNTech booster shots for all individuals older than 16 by a 16-2 vote Friday afternoon. Soon after, however, the agency posed committee members a new question limiting booster use to the 65-and-older population and individuals at high risk of disease due to occupational exposure or comorbidities.

Lat­est news: It’s a no on uni­ver­sal boost­ers; Pa­tient death stuns gene ther­a­py field; In­side Tril­li­um’s $2.3B turn­around; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Next week is shaping up to be a busy one, as our editor-in-chief John Carroll and managing editor Kyle Blankenship lead back-to-back discussions with a great group of experts to discuss the weekend news and trends. John will be spending 30 minutes with Jake Van Naarden, the CEO of Lilly Oncology, and Kyle has a brilliant panel lined up: Harvard’s Cigall Kadoch, Susan Galbraith, the new head of cancer R&D at AstraZeneca, Roy Baynes at Merck, and James Christensen at Mirati. Don’t miss out on the action — sign up here.

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As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

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Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

Merck Research Laboratories CMO Roy Baynes

Mer­ck­'s Keytru­da un­corks full da­ta on lat­est ad­ju­vant win — this time in melanoma — adding bricks to ear­ly can­cer wall

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A combination of Keytruda and chemotherapy with or without Roche’s Avastin cut the risk of death by 33% over chemo with or without Avastin (p=<0.001) in first-line patients with persistent, recurrent or metastatic cervical cancer, according to full data from the Phase III KEYNOTE-826 study presented Saturday at #ESMO21.

EQRx chairman Alexis Borisy and CEO Melanie Nallichieri

EQRx, CStone un­furl full lung can­cer da­ta for PD-L1 drug in what the part­ners are call­ing a first

As a self-stylized drug pricing disruptor, EQRx has high hopes for its lead PD-(L)1 to offer proof of concept for the entire business model. After touting a win back in May, the biotech is back with full data in lung cancer that could back up an approval.

Patients dosed with EQRx and CStone Pharmaceuticals’ sugemalimab posted median progression-free survival of 9 months compared with 5.8 months for patients given placebo (p=0.0026), according to full data from the Phase III GEMSTONE-301 study in Stage III non-small cell lung cancer set to be presented at this weekend’s #ESMO21.

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As­traZeneca touts Imfinzi im­munother­a­py com­bos for lung can­cer in push to dri­ve PD-L1 drug up­take

Facing the big dogs in the PD-(L)1 space, AstraZeneca has taken its own contender Imfinzi into blockbuster territory in its four years on the market but sees even bigger things for the drug. Combinations could be the key, and early results from a mid-stage test are adding some fuel to that strategy.

Imfinzi combined with one of two investigational immunotherapies — a CD73 antibody dubbed oleclumab or an Innate’s anti-NGK2a named monalizumab — topped Imfinzi alone in terms of overall response and progression-free survival in patients with stage III non-small cell lung cancer whose tumors had not worsened during concurrent chemoradiation, according to interim data from the Phase II COAST trial set to be presented at #ESMO21.