Bio­gen push­es for broad CMS cov­er­age of Alzheimer's drug — while Eli Lil­ly looks to es­cape an NCD

The nine-month quest for CMS to fig­ure out how (or how not) to cov­er Bio­gen’s new Alzheimer’s drug Aduhelm, and po­ten­tial­ly more amy­loid-tar­get­ed mon­o­clon­al an­ti­bod­ies, kicked off in earnest on Tues­day with an open pub­lic hear­ing of com­ments from var­i­ous stake­hold­ers stress­ing the pros and cons of cov­er­ing this new, pricey drug with un­known clin­i­cal ben­e­fits.

Bio­gen and its af­fil­i­ates stressed the need for a quick and pos­i­tive Na­tion­al Cov­er­age De­ter­mi­na­tion from CMS as oth­er physi­cians and a speak­er from ICER called on CMS to not cov­er the drug or to lim­it cov­er­age in cer­tain ways as Bio­gen’s clin­i­cal tri­als didn’t show strong signs of clin­i­cal ben­e­fit, the $56,000 an­nu­al price tag doesn’t match those ben­e­fits, and as the tri­als didn’t ad­dress a di­verse group of pop­u­la­tions, like African Amer­i­cans or Lat­inx, who are fre­quent­ly af­fect­ed by Alzheimer’s.

While an all-out re­jec­tion in cov­er­age from CMS seems un­like­ly giv­en the his­to­ry of the cen­ters’ pri­or NCDs on CAR-T ther­a­pies and oth­er treat­ments and de­vices, Bio­gen opened Tues­day’s call with the first two com­ments from ex­ec­u­tives re­it­er­at­ing the ne­ces­si­ty for wide­spread and ear­ly cov­er­age.

Ma­ha Rad­hakr­ish­nan

“Ther­a­py should not be lim­it­ed to aca­d­e­m­ic cen­ters as many un­der­served and un­der-rep­re­sent­ed pa­tients don’t have ac­cess to these cen­ters,” Ma­ha Rad­hakr­ish­nan, CMO at Bio­gen, said.

An ear­li­er Bio­gen ex­ec called on the agency to en­cour­age MACs to cov­er Aduhelm at the lo­cal lev­el while the NCD process is on­go­ing, echo­ing com­ments from an anony­mous Bio­gen em­ploy­ee who told End­points News last week that he de­clined to use his re­la­tion­ship with a large aca­d­e­m­ic med­ical cen­ter to en­cour­age lo­cal Medicare pol­i­cy­mak­ers to cov­er Aduhelm as he didn’t think it was eth­i­cal.

But it was in the writ­ten com­ments (see be­low) where a strong force of aca­d­e­mics and oth­er Alzheimer’s re­searchers called on Medicare to do what FDA didn’t do, and re­ject cov­er­age for Aduhelm

Not all amy­loid drugs?

But it was an Eli Lil­ly doc­tor who called on CMS to not make any rash de­ci­sion that pre­ma­ture­ly short­changes the en­tire class of amy­loid-tar­get­ed drugs.

Lil­ly said late last month it’s fil­ing its amy­loid-tar­get­ed do­nanemab with the FDA lat­er this year based on Phase II da­ta now that the FDA con­sid­ers amy­loid clear­ance rea­son­ably like­ly to lead to cog­ni­tive ben­e­fit.

Brandy Matthews

Brandy Matthews, a neu­rol­o­gist and se­nior med­ical ad­vis­er to Lil­ly, not­ed the com­pa­ny’s “con­cern” at the out­set of its pub­lic com­ment that a class-based NCD “might be pre­ma­ture at this point” be­cause dif­fer­ent mon­o­clon­al an­ti­bod­ies are at dif­fer­ent stages of de­vel­op­ment and ev­i­dence might be­come avail­able dur­ing or af­ter the NCD.

Each Alzheimer’s drug should be eval­u­at­ed on its own amy­loid plaque re­duc­tion, safe­ty pro­file and clin­i­cal ben­e­fit, Matthews said. CMS cov­er­age poli­cies to eval­u­ate ther­a­peu­tics should oc­cur for each one, she said while urg­ing CMS for flex­i­bil­i­ty that does not lim­it ac­cess to fu­ture ther­a­pies.

“Lim­i­ta­tions on the first ap­proved ther­a­py should not au­to­mat­i­cal­ly ap­ply to fu­ture ther­a­pies,” she said.

As Bio­gen-fund­ed aca­d­e­mics sig­naled how to use Aduhelm on Tues­day, Matthews called on CMS to use the en­roll­ment cri­te­ria for each clin­i­cal tri­al as the start­ing point for cov­er­age.

Flood of neg­a­tive writ­ten com­ments

Out­side of Tues­day’s call, a pile-up of writ­ten com­ments on the na­tion­al cov­er­age analy­ses shows just how many think FDA was wrong to ap­prove Aduhelm and that CMS should not pro­vide cov­er­age.

Roger Al­bin, a pro­fes­sor of neu­rol­o­gy at the Uni­ver­si­ty of Michi­gan, wrote, “The da­ta sup­port­ing util­i­ty of ad­u­canum­ab for Alzheimer Dis­ease isn’t even weak. The FDA should nev­er have ap­proved this agent. CMS should de­cline to pro­vide cov­er­age for ad­u­canum­ab treat­ment.”

James Lah, di­rec­tor of the Cog­ni­tive Neu­rol­o­gy Pro­gram at Emory Uni­ver­si­ty School of Med­i­cine, added, “The FDA made sev­er­al mis­takes in re­view­ing ad­u­canum­ab, but per­haps fore­most was their fail­ure to re­quest the ad­vi­so­ry pan­el con­sid­er the op­tion of Ac­cel­er­at­ed Ap­proval. Had they done so, I sus­pect there would have been fruit­ful dis­cus­sion to in­form the many de­ci­sions now left to us as providers and pay­ors to an­swer.”

“The fact that this drug was FDA ap­proved is a trav­es­ty; please do not make it worse. The mon­ey that would cov­er this drug could go to much bet­ter use for those pa­tients and care­givers,” wrote An­drea Bial, pro­gram di­rec­tor at the Loy­ola-Hines Geri­atric Med­i­cine Fel­low­ship Pro­gram.

Bri­enne Min­er, as­so­ciate pro­fes­sor of geri­atrics at Yale Uni­ver­si­ty, wrote, “I am deeply trou­bled by the pres­sure to use an un­proven and po­ten­tial­ly dan­ger­ous treat­ment in our pa­tients, many of whom are des­per­ate to try any­thing that might give them hope. I don’t see how they can re­al­ly make an in­formed de­ci­sion here.”

Saman­tha Hold­en, an as­sis­tant pro­fes­sor in the De­part­ment of Neu­rol­o­gy at the Uni­ver­si­ty of Col­orado, al­so not­ed, “As a cog­ni­tive neu­rol­o­gist and de­men­tia spe­cial­ist, I have long wait­ed for an ef­fec­tive dis­ease-mod­i­fy­ing ther­a­py for my pa­tients. I have not been con­vinced that ad­u­canum­ab is that drug. I am ex­treme­ly con­cerned re­gard­ing the pre­sent­ed da­ta, con­flict­ing re­sults be­tween EN­GAGE and EMERGE, the costs, and po­ten­tial to in­crease in­equities in neu­ro­log­i­cal care in this coun­try.”

Michael Car­ome, di­rec­tor of the non­prof­it Pub­lic Cit­i­zen’s Health Re­search Group, al­so called on CMS to ex­clude cov­er­age for Aduhelm, ar­gu­ing that the drug “can­not pos­si­bly be deemed rea­son­able and nec­es­sary” as “based on the cur­rent­ly avail­able sci­en­tif­ic ev­i­dence, re­duc­tion of amy­loid-be­ta plaques in the brain it­self is not a clin­i­cal­ly mean­ing­ful out­come.”

Mov­ing for­ward, the ini­tial writ­ten pub­lic com­ment pe­ri­od ends on Au­gust 11, and then CMS will re­view those com­ments over 6 months in de­vel­op­ing a pro­posed NCD and mem­o­ran­dum. No lat­er than Jan. 12, 2022, the pro­posed NCD will be avail­able, and the pub­lic will have one more 30-day com­ment pe­ri­od. A fi­nal NCD will be com­plet­ed no lat­er than April 12, 2022, CMS said Tues­day.

Medicare pay­ment rates and codes are gen­er­at­ed out­side the NCD process.

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

Forge Biologics has developed a bespoke affinity chromatography platform approach that factors in unique vector combinations to streamline development timelines and assist our clients in efficiently entering the clinic. By leveraging our experience with natural and novel serotypes and transgene conformations, we are able to accelerate affinity chromatography development by nearly 3-fold. Many downstream purification models are serotype-dependent, demanding unique and time-consuming development strategies for each AAV gene therapy product1. With the increasing demand to propel AAV gene therapies to market, platform purification methods that support commercial-scale manufacturing of high-quality vectors with excellent safety and efficacy profiles are essential.

Feng Zhang (Susan Walsh/AP Images)

In search of new way to de­liv­er gene ed­i­tors, CRISPR pi­o­neer turns to mol­e­c­u­lar sy­ringes

Bug bacteria are ruthless.

Some soil bacteria have evolved tiny, but deadly injection systems that attach to insect cells, perforate them and release toxins inside — killing a bug in just a few days’ time. Scientists, on the other hand, want to leverage that system to deliver medicines.

In a paper published Wednesday in Nature, MIT CRISPR researcher Feng Zhang and his lab describe how they engineered these syringes made by bacteria to deliver potential therapies like toxins that kill cancer cells and gene editors. With the help of an AI program, they developed syringes that can load proteins of their choice and selectively target human cells.

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Mathai Mammen, FogPharma's next CEO

Math­ai Mam­men hands in J&J's R&D keys to lead Greg Ver­dine’s Fog­Phar­ma 

In the early 1990s, Mathai Mammen was a teaching assistant in Greg Verdine’s Science B46 course at Harvard. In June, the former R&D head at Johnson & Johnson will succeed Verdine as CEO, president and chair of FogPharma, the same month the seven-year-old biotech kickstarts its first clinical trial.

After leading R&D at one of the largest drugmakers in the world, taking the company through more than half a dozen drug approvals in the past few years, not to mention a Covid-19 vaccine race, Mammen departed J&J last month and will take the helm of a Cambridge, MA biotech attempting to go after what Verdine calls the “true emperor of all oncogenes” — beta-catenin.

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See­los Ther­a­peu­tics 'tem­porar­i­ly' stops study in rare neu­ro dis­or­der for busi­ness rea­sons

Microcap biotech Seelos Therapeutics is halting enrollment of its study in spinocerebellar ataxia type 3 (also known as Machado-Joseph disease) because of “financial considerations,” and in order to focus on other studies, the company said today, adding that the pause would be temporary.

The study will continue with the patients who have already enrolled, and the data from them will be used to decide whether to continue enrolling others in the future.

Alec­tor cuts 11% of work­force as it dou­bles down on late-stage neu­ro pro­grams part­nered with GSK, Ab­b­Vie

A month after revealing plans to concentrate on its late-stage immuno-neurology pipeline, Alector is trimming its headcount by 11%.

The layoffs will impact around 30 employees across the organization, the company disclosed in an SEC filing, adding that the plan will “better align the company’s resources” with the new strategy. With $712.9 million in cash, cash equivalents and investments as of the end of 2022, Alector believes the reserves will now get it through 2025.

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Hugo Peris, Spiral Therapeutics CEO

Hear­ing-fo­cused biotech grabs trio of pro­grams from Oton­o­my's fire sale

Otonomy may be shutting down, but the lessons learned there will live on at another biotech working on new treatments for hearing loss.

San Francisco-based Spiral Therapeutics has bought certain assets related to three of Otonomy’s programs, ranging from data, patent rights, and know-how to inventory. That includes data around Otonomy’s twice-failed lead program, OTO-104 (Otividex), a sustained-exposure formulation of dexamethasone.

Jeff Bluestone (R), Sonoma Biotherapeutics CEO

Jef­frey Blue­stone brings his start­up haul to $400M+, join­ing forces with Re­gen­eron on cell ther­a­pies

These days, when Jeffrey Bluestone gets together with his contemporaries in science, the conversation often turns to retirement plans.

But a little more than three years ago, Bluestone reached a momentous turning point in his career, exiting a prestigious post at UCSF, where he had spent decades in the scientific pursuit of new therapies. And it had nothing to do with retirement anytime in the near future.

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CSL CEO Paul McKenzie (L) and CMO Bill Mezzanotte

Q&A: New­ly-mint­ed CSL chief ex­ec­u­tive Paul McKen­zie and chief med­ical of­fi­cer Bill Mez­zan­otte

Paul McKenzie took over as CEO of Australian pharma giant CSL this month, following in the footsteps of long-time CSL vet Paul Perreault.

With an eye on mRNA, and quickly commercializing its new, $3.5 million-per-shot gene therapy for hemophilia B, McKenzie and chief medical officer Bill Mezzanotte answered some questions from Endpoints News this afternoon about where McKenzie is going to take the company and what advances may be coming to market from CSL’s pipeline. Below is a lightly edited transcript.

Boehringer re­ports ro­bust sales led by type 2 di­a­betes and pul­monary drugs, promis­es more to come high­light­ing obe­si­ty

Boehringer Ingelheim reported human pharma sales of €18.5 billion on Wednesday, led by type 2 diabetes and heart failure drug Jardiance and pulmonary fibrosis med Ofev. Jardiance sales reached €5.8 billion, growing 39% year over year, while Ofev took in €3.2 billion, notching its own 20.6% annual jump.

However, Boehringer is also looking ahead with its pipeline, estimating “In the next seven years the company expects about 20 regulatory approvals in human pharma.”