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.

The FDA today approved Emergent BioSolutions’ Narcan brand naloxone nasal spray for over-the-counter sales. The nod was expected and comes on the heels of a unanimous 19-0 advisory committee vote in favor of approval last month.

The move to OTC means the opioid overdose reversal agent will now be available on grocery, convenience and gas stations shelves, as well as potentially for purchase online.

The mRNA player Moderna is further cementing its presence on the African continent.

Moderna announced on Thursday that it has finalized an agreement with Kenya’s government to partner up and bring an mRNA manufacturing facility to the east African nation. The new facility aims to manufacture up to 500 million doses of vaccines annually. Moderna also said the new facility will have the ability to spike its production capabilities to respond to public health emergencies on the continent or globally.

Dallas-based biotech Nanoscope Therapeutics unveiled Phase II results on its gene therapy for a rare eye disease Thursday morning.

In the RESTORE trial, 18 patients with retinitis pigmentosa got a gene therapy called MCO-010 while nine got placebo. On a vision test called the MLYMT, the treatment group had a one-point greater change over one year in their score compared to the placebo group, the primary endpoint of the study. However, the 95% confidence interval was 0.0 to 3.0, meaning the result was not statistically significant. The p-value was not provided.

When Vigil Neuroscience filed its IPO papers in late 2021, the biotech revealed that the FDA had just cleared its Phase I trial — but with a partial clinical hold that limited dosing to under a certain level.

More than a year later, the FDA has lifted the hold.

Vigil is now free to dose VGL101, an antibody targeting TREM2, at levels higher than 20 mg/kg in its ongoing and future clinical trials in patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), an inherited condition that affects the brain and spinal cord.