FDA+ roundup: ALS bill would provide $100m annually to access potential drugs; FDA needs to better enforce ClinicalTrials.gov reporting, researchers say

The House En­er­gy & Com­merce Com­mit­tee be­gan mark­ing up a dozen bills on Wednes­day morn­ing in­clud­ing one that would re­quire the FDA to craft a five-year ac­tion plan for fos­ter­ing the de­vel­op­ment of drugs that im­prove or ex­tend the lives of peo­ple liv­ing with rare neu­rode­gen­er­a­tive dis­eases.

Rare neu­rode­gen­er­a­tive dis­eases, like amy­otroph­ic lat­er­al scle­ro­sis or ALS, have been his­tor­i­cal­ly very dif­fi­cult to treat. But this bi­par­ti­san bill, in­tro­duced by Rep. Mike Quigley (D-IL), will pro­vide $100 mil­lion for each of fis­cal years 2022 through 2026 to help HHS award grants to fa­cil­i­tate ac­cess to in­ves­ti­ga­tion­al drugs that di­ag­nose or treat ALS.

The FDA will award grants to pub­lic and pri­vate en­ti­ties to cov­er the costs of R&D for drugs that di­ag­nose or treat ALS and oth­er se­vere­ly de­bil­i­tat­ing neu­rode­gen­er­a­tive dis­eases, the bill text says.

In ad­di­tion, HHS would have to es­tab­lish the Pub­lic-Pri­vate Part­ner­ship for Neu­rode­gen­er­a­tive Dis­eases be­tween the NIH, FDA, and at least one el­i­gi­ble en­ti­ty (gen­er­al­ly, an in­sti­tu­tion of high­er ed­u­ca­tion or a non­prof­it or­ga­ni­za­tion). The bill, first in­tro­duced last sum­mer, al­so has a com­pan­ion bill in the Sen­ate, in­tro­duced by Chris Coons (D-DE).

FDA needs to bet­ter en­force Clin­i­cal­Tri­als.gov re­port­ing, Yale re­searchers write in JA­MA

De­spite clear in­struc­tions on how and when to re­port clin­i­cal tri­al re­sults, about 60% of tri­als fail to re­port re­sults on time and more than 30% (among al­most 3000 clin­i­cal tri­als with pri­ma­ry com­ple­tion dates be­tween Jan. 2017, and Jan. 2021) have not yet re­port­ed re­sults. That lack of re­port­ing means the FDA needs to beef up its en­force­ment ef­forts, re­searchers from Yale wrote re­cent­ly in a JA­MA view­point.

For its part, the FDA iden­ti­fies po­ten­tial vi­o­la­tions of the law gov­ern­ing the re­port­ing of the re­sults through in­ves­ti­ga­tions and third-par­ty com­plaints, and then at its dis­cre­tion, may is­sue a Pre­lim­i­nary No­tice of Non­com­pli­ance in­form­ing re­spon­si­ble par­ties of po­ten­tial vi­o­la­tions.

Yale re­searchers used FOIA to find that the FDA has on­ly is­sued 58 of its pre­lim­i­nary no­tices of non­com­pli­ance from 2013 through April 29, which they said is ‘a tiny frac­tion of the thou­sands of FDAAA-ap­plic­a­ble clin­i­cal tri­als iden­ti­fied as non­com­pli­ant with re­sults in­for­ma­tion re­port­ing re­quire­ments as of Jan­u­ary 2021.’

So how can the FDA help? The re­searchers say that in­stead of re­ly­ing on in­con­sis­tent BI­MO in­ves­ti­ga­tions and third-par­ty com­plaints to iden­ti­fy non­com­pli­ant tri­als, the FDA could in­stead use a con­tin­u­al­ly up­dat­ed list of FDAAA 801 prob­lems main­tained by the NIH. In ad­di­tion, FDA should pub­li­cize the no­tices more fre­quent­ly and en­sure that they present clear time­lines for fur­ther en­force­ment ac­tions if re­sults re­main un­re­port­ed.

‘The FDA can and should har­ness its en­force­ment tools to en­sure time­ly sub­mis­sion of tri­al re­sults in­for­ma­tion to Clin­i­cal­Tri­als.gov. By do­ing so, the FDA could bring im­por­tant miss­ing re­sults to light and demon­strate its com­mit­ment to pro­tect­ing pa­tients through clin­i­cal tri­al trans­paren­cy,’ they wrote.

Re­gen­eron and No­var­tis seek tweaks to ICH’s S12 guid­ance for gene ther­a­pies

No­var­tis, Re­gen­eron and oth­ers are sug­gest­ing tweaks in re­cent­ly re­leased com­ments on a re­cent guid­ance from ICH, known as S12, which deals with the non­clin­i­cal biodis­tri­b­u­tion con­sid­er­a­tions for gene ther­a­pies.

No­var­tis, for in­stance, took is­sue with the fact that vi­ral shed­ding is list­ed as ‘out of scope’ from the S12 guid­ance.

‘We be­lieve that it is a missed op­por­tu­ni­ty in not in­clud­ing this top­ic, par­tic­u­lar­ly as some would con­sid­er shed­ding as part of the ‘dis­tri­b­u­tion’ of a gene ther­a­py vec­tor. In ad­di­tion, there ex­ists sig­nif­i­cant health au­thor­i­ty di­ver­gence in opin­ion with re­spect to whether shed­ding should be as­sessed in non­clin­i­cal stud­ies. Please con­sid­er adding shed­ding with­in this guid­ance,’ Tim­o­thy MacLach­lan, ex­ec­u­tive di­rec­tor of pre-clin­i­cal safe­ty, and Jes­si­ca Riz­zo, reg­u­la­to­ry pol­i­cy man­ag­er, wrote.

And while the guid­ance sug­gests that non­clin­i­cal BD should be as­sessed pri­or to the ini­ti­a­tion of a clin­i­cal tri­al, No­var­tis won­ders what to do in a sit­u­a­tion where a spon­sor is at­tempt­ing to open an IND with an in­ter­im look on a much longer-term an­i­mal study, where spon­sors would get ad­di­tion­al in­for­ma­tion for the clin­i­cal tri­al from that an­i­mal study.

Re­gen­eron, mean­while, is seek­ing clar­i­ty on the ICH rec­om­men­da­tion for sam­ple col­lec­tion of a core pan­el of tis­sues/bioflu­ids. The New York biotech added:

The guid­ance could be read as rec­om­mend­ing that all of the list­ed tis­sue sam­ples should be col­lect­ed. In­stead, Re­gen­eron pro­pos­es that the guid­ance should rec­om­mend a risk-based ap­proach to guide which sam­ples should be col­lect­ed along with ap­pro­pri­ate jus­ti­fi­ca­tion pro­vid­ed by the de­vel­op­er, based on knowl­edge of the gene ther­a­py prod­uct and its tar­get(s). The same risk-based ap­proach could be used to de­ter­mine which of the col­lect­ed tis­sues would be an­a­lyzed. Do­ing so would al­low de­vel­op­ers to iden­ti­fy those sam­ple tis­sues that can pro­vide ear­ly sci­en­tif­ic ev­i­dence that could in­form fu­ture in-hu­man tri­als.

FDA must prompt­ly pun­ish Min­neso­ta Hos­pi­tal re­searchers, Pub­lic Cit­i­zen says

Pub­lic Cit­i­zen, a non­prof­it con­sumer ad­vo­ca­cy or­ga­ni­za­tion, filed a cit­i­zen pe­ti­tion on Wednes­day with the FDA, call­ing on the agency to take swift en­force­ment ac­tion against sev­er­al Min­neso­ta doc­tors cit­ed in re­cent warn­ing let­ters who con­duct­ed clin­i­cal re­search of dan­ger­ous drugs with­out the prop­er au­tho­riza­tions in place.

Ac­cord­ing to a warn­ing let­ter sent by FDA in Oc­to­ber, doc­tors nev­er filed the ap­pro­pri­ate INDs for the ke­t­a­mine tri­als with the FDA, as re­quired by law, and didn’t write ap­pro­pri­ate pro­to­cols to en­sure that chil­dren and preg­nant women weren’t en­rolled. The tri­als al­so didn’t ex­clude those who were un­der the in­flu­ence of in­tox­i­cants, in whom the use of ke­t­a­mine is cau­tioned.

‘A slap-on-the-wrist ap­proach for such non­com­pli­ance that sig­nif­i­cant­ly vi­o­lat­ed the rights of more than 1,700 vul­ner­a­ble hu­man sub­jects and en­dan­gered the health of safe­ty of many of these sub­jects will not suf­fice,’ Pub­lic Cit­i­zen wrote.

For years, paper-based processes and individual point solutions dominated the clinical research landscape, and patient participation in clinical trials was largely an in-person engagement. But when the COVID-19 pandemic took a stronghold, traditional clinical trial methods emerged as inadequate, putting clinical trials and the life sciences industry at a crossroads. Practically overnight, the industry had to rapidly shift to decentralized clinical trial methods, while maintaining data quality and regulatory compliance.

Al Sandrock (Biogen via Youtube)

Two years after Al Sandrock jumped from CMO to the top post in R&D — and just months after the hyper-controversial approval of the experimental Alzheimer’s drug aducanumab (Aduhelm) — Sandrock is planning to step out of his long career at Biogen.

Late Monday evening the big biotech put out word that Sandrock, a longtime fixture in the company after a 23-year stint, is hitting the exit.

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A few weeks after Jennifer Doudna introduced CRISPR/Cas9 genome editing to the world, one of her old students decided to take the central part of the biology-altering invention and kill it.

CRISPR/Cas9, as the name implies, is a two-part system: a string of letters called a guide RNA, that says where to cut the DNA. And an enzyme, Cas9, that does the cutting. Often compared to molecular scissors, it was the first system that allowed researchers to cut DNA with ease and precision, promising potential cures for genetic diseases such as sickle cell and cystic fibrosis.

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Rep. Diana DeGette (D-CO) (Alex Brandon/AP Images)

Reps. Fred Upton (R-MI) and Diana DeGette (D-CO) on Tuesday unveiled the second iteration of their mammoth 21st Century Cures Act, a wide-ranging, mostly pro-pharma law signed by former President Obama that pushed the FDA in certain directions on real-world data and other hot button issues.

This time around there’s a provision to fund a $6.5 billion (on par with Biden’s request) research center at NIH to speed new treatments and make riskier investments. Similar to DARPA, the new NIH division to be known as ARPA-H, would be run by a small group of program managers with more latitude to pursue high-risk, high-reward projects.

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Michel Vounatsos, Biogen CEO (Credit: World Economic Forum/Valeriano Di Domenico)

Following an oral explanation held at the November meeting of the EMA’s human medicines committee, Biogen received ‘a negative trend vote’ on its marketing application for its controversial Alzheimer’s drug aducanumab, the company said Wednesday morning.

The setback is just the latest in a string of negatives — from an anemic launch to rejection of coverage from the VA — since the surprising June approval of the drug by the FDA that led to multiple resignations from an advisory committee that unanimously rejected it.

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Catherine Stehman-Breen and Vic Myer, Chroma CEO and CSO

A handful of the world’s most prominent gene editing-focused academics have been working for over a year on a new company built around a new approach for modifying DNA to treat disease. Known as Chroma Medicine, it launched on Wednesday with $125 million in early funding from Atlas, Newpath, Cormorant and several other VCs.

Chroma will focus on a markedly different way of modifying the genome than most of the gene editing biotechs that have arisen since CRISPR was pioneered nearly a decade ago. Instead of trying to erase or rewrite portions of a patient’s actual DNA — those As, Ts, Cs and Gs — Chroma will try to change the way that DNA is expressed in the cell.

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Chiquita Brooks-LaSure (Photo by Caroline Brehman/CQ Roll Call via AP Images)

Although sales of Biogen’s expensive new Alzheimer’s drug have been anemic since the approval in June, the prospect of CMS eventually paying for it opens up a billion-dollar can of worms, and already has the agency defending some premium and deductible increases for seniors.

CMS explained late Friday that Medicare Part B will have to increase its standard monthly premium — from $148.50 in 2021 to $170.10 in 2022 — in part because of the massive spending that could occur should the agency sign off on a national coverage decision for the drug, known as Aduhelm, and its $56,000 annual price tag next year.

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Patients and families tell their Parkinson’s disease stories in new Acadia and StoryCorp campaign (via Acadia/StoryCorps))

Acadia Pharmaceuticals is putting the power of storytelling to work for Parkinson’s disease. While storytelling in general is often used in pharma marketing to help explain the realities of health conditions, Acadia is teaming up with the storytelling powerhouse StoryCorps for the new campaign.

Called ‘Yours, Truly,’ the work centers on pairs of people in poignant conversations relaying the stories of their own or their loved ones’ Parkinson’s experience.

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The US Securities and Exchange Commission has launched a probe into claims that Cassava Sciences, an Austin-based drug developer, manipulated data key to its case for its experimental Alzheimer’s drug simufilam, the Wall Street Journal reported Wednesday.

The report comes just two days after Cassava in an SEC filing revealed that ‘certain government agencies’ had asked the biotech for documentation. It wasn’t clear which agencies were inquiring or what information they sought, and Cassava went out of its way to say the requests weren’t accusations of wrongdoing.

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