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.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

All about Omi­cron; We need more Covid an­tivi­rals; GSK snags Pfiz­er’s vac­cine ex­ec; Janet Wood­cock’s fu­ture at FDA; and more

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Usama Malik

Ex-Im­munomedics CFO charged with in­sid­er trad­ing, faces up to 20 years in prison af­ter al­leged­ly tip­ping off girl­friend and rel­a­tives of a PhI­II suc­cess

The former CFO of Immunomedics, who helped steer the company to its $21 billion buyout by Gilead last year, has been charged with insider trading, the Department of Justice announced Thursday.

Usama Malik tipped off his then-girlfriend and four others that a Phase III study for Trodelvy would be stopped early four days before Immunomedics publicly announced the result in April 2020, DoJ alleged in its complaint. The individuals then purchased Immunomedics shares, selling them after the news broke and Immunomedics’ stock price doubled.

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Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

As Omi­cron spread looms, oral an­tivi­rals ap­pear to be one of the best de­fens­es — now we just need more

After South African scientists reported a new Covid-19 variant — dubbed Omicron by the WHO — scientists became concerned about how effective vaccines and monoclonal antibodies might be against it, which has more than 30 mutations in the spike protein.

“I think it is super worrisome,” Dartmouth professor and Adagio co-founder and CEO Tillman Gerngross told Endpoints News this weekend. Moderna CEO Stéphane Bancel echoed similar concerns, telling the Financial Times that experts warned him, “This is not going to be good.”

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Biospec­i­men M&A: Dis­cov­ery ac­quires Al­bert Li's he­pa­to­cyte project; PhI­II tri­al on Bay­er's Nube­qa reached pri­ma­ry end­point

Discovery Life Sciences has acquired what claims to be the Maryland-based host of the world’s largest hepatocyte inventory, known as IVAL, to help researchers select more effective and safer drug candidates in the future.

The combined companies will now serve a wider range of drug research and development scientists, according to Albert Li, who founded IVAL in 2004 and is set to join the Discovery leadership team as the CSO of pharmacology and toxicology.

Pfiz­er, Am­gen and Janssen seek fur­ther clar­i­ty on FDA's new ben­e­fit-risk guid­ance

Three top biopharma companies are seeking more details from the FDA on how the agency conducts its benefit-risk assessments for new drugs and biologics.

While Pfizer, Amgen and Janssen praised the agency for further spelling out its thinking on the subject in a new draft guidance, including a discussion of patient experience data as part of the assessment, the companies said the FDA could’ve included more specifics in the 20-page draft document.

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Janet Woodcock (AP Images)

Janet Wood­cock plots her fu­ture at FDA, with se­nior ad­vi­sor role to fall back on if Califf wins con­fir­ma­tion

Acting FDA commissioner Janet Woodcock has been the face of just about every drug approval decision at the agency since the turn of the century. Since the pandemic began, she’s moved between the top of the drugs center to the head of therapeutics at Operation Warp Speed, leading the drive for work on Covid-targeted mAbs and antivirals.

Looking forward — and pending a quick Senate confirmation to cement Rob Califf’s return to the top of FDA early next year — Woodcock’s role at the agency will again be in flux.

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Richard Pazdur (via AACR)

Ac­cel­er­at­ed ap­proval re­forms need mean­ing­ful con­fir­ma­to­ry tri­al im­prove­ments, pro­fes­sors write in Sci­ence

Outside of Covid-19, 2021 has been the year of the accelerated approval.

Beginning last spring, FDA openly challenged six “dangling” accelerated approvals (hadn’t confirmed their clinical benefit yet), three of which were later pulled by the companies.

Then in June, FDA pulled out the accelerated approval pathway, seemingly out of nowhere, to sign off on Biogen’s controversial Alzheimer’s drug Aduhelm. It hadn’t even been mentioned at the drug’s adcomm.

With on­ly burns to show in gene ther­a­py, Astel­las inks deal with AAV spe­cial­ist Dyno in push for a bet­ter cap­sid

On the hunt for a better AAV capsid for gene therapy, Eric Kelsic’s Dyno Therapeutics has set itself apart with its focus on machine learning to help speed discovery. Now, Japanese drugmaker Astellas — fresh off a slate of gene therapy burns — is taking a bet on Dyno as it looks to the future.

Astellas and Dyno will work together as part of an R&D pact to develop next-gen AAV vectors for gene therapy using Dyno’s CapsidMap platform directed at skeletal and cardiac muscle, the companies said Wednesday. Under the terms of the deal, Dyno will design AAV capsids for gene therapy, while Astellas will be responsible for conducting preclinical, clinical and commercialization activities for gene therapy product candidates using the capsids.