Fab­ry dis­ease: FDA drafts drug de­vel­op­ment guid­ance

The FDA on Wednes­day is­sued draft guid­ance pro­vid­ing rec­om­men­da­tions to drug­mak­ers on clin­i­cal tri­al de­sign and el­i­gi­bil­i­ty cri­te­ria for prod­ucts to treat Fab­ry dis­ease.

Fab­ry dis­ease is a rare in­her­it­ed dis­or­der caused by a de­fi­cien­cy of the lyso­so­mal en­zyme al­pha-galac­tosi­dase A (α-Gal A). Ac­cord­ing to the FDA, pa­tients with Fab­ry dis­ease ex­pe­ri­ence chron­ic gas­troin­testi­nal and neu­ro­path­ic symp­toms and pro­gres­sive or­gan dam­age that even­tu­al­ly caus­es chron­ic re­nal dis­ease, re­nal fail­ure, car­dio­vas­cu­lar dis­ease and strokes.

There are on­ly two prod­ucts ap­proved by the FDA to treat Fab­ry dis­ease, Sanofi Gen­zyme’s en­zyme re­place­ment ther­a­py (ERT) Fab­razyme (agal­si­dase be­ta) and Am­i­cus Ther­a­peu­tics’ Galafold (mi­gala­s­tat), which was grant­ed ac­cel­er­at­ed ap­proval in Au­gust 2018. A sec­ond ERT drug, Shire’s Re­pla­gal (agal­si­dase al­fa) is ap­proved in Eu­rope, but was with­drawn from con­sid­er­a­tion in the US in 2012 af­ter the FDA in­di­cat­ed the com­pa­ny would need to con­duct ad­di­tion­al clin­i­cal tri­als to sup­port ap­proval.

The FDA says it hopes the draft guid­ance will “fos­ter greater ef­fi­cien­cy in drug de­vel­op­ment in this rare dis­ease with the goal of en­hanc­ing clin­i­cal tri­al da­ta qual­i­ty.”

In the 7-page draft guid­ance, the FDA sets out its ex­pec­ta­tions for clin­i­cal tri­al el­i­gi­bil­i­ty cri­te­ria and tri­al de­sign, in­clud­ing con­sid­er­a­tions for ef­fi­ca­cy end­points for treat­ments tar­get­ing spe­cif­ic man­i­fes­ta­tions of the dis­ease.

As for el­i­gi­bil­i­ty cri­te­ria, the FDA says that all pa­tients should have a “con­firmed di­ag­no­sis of [Fab­ry dis­ease] based on both bio­chem­i­cal test­ing and mol­e­c­u­lar test­ing” and that clin­i­cal tri­als should en­roll both male and fe­male pa­tients, pro­vid­ing spe­cif­ic en­rol­ment cri­te­ria for pa­tients of each sex. The FDA al­so says that spon­sors should con­sid­er en­rolling pe­di­atric pa­tients “as ear­ly as fea­si­ble.”

Due to how rare Fab­ry dis­ease is, the FDA says that a sin­gle ad­e­quate and well-con­trolled tri­al “show­ing a clin­i­cal­ly mean­ing­ful treat­ment ef­fect on core clin­i­cal as­pects” of the dis­ease, plus con­fir­ma­to­ry ev­i­dence, is suf­fi­cient for ap­proval.

The FDA al­so says that spon­sors should em­ploy a par­al­lel group de­sign with ei­ther a place­bo or ac­tive con­trol group and con­sid­er strat­i­fy­ing pa­tients by age and sex.

For treat­ments meant to slow or halt dis­ease progress rather than re­verse the dis­ease, the FDA says spon­sors should en­sure the tri­al is con­duct­ed over a long enough pe­ri­od to ob­serve dis­ease pro­gres­sion, not­ing that spe­cial con­sid­er­a­tion should be tak­en with re­gards to long-term fol­low up for gene ther­a­pies.

The draft guid­ance al­so pro­vides con­sid­er­a­tions for end­point se­lec­tion for prod­ucts tar­get­ing spe­cif­ic as­pects of Fab­ry dis­ease, in­clud­ing drugs to treat neu­ro­path­ic and gas­troin­testi­nal symp­toms, re­nal dis­ease and car­diac dis­ease.

FDAFed­er­al Reg­is­ter No­tice


RAPS: First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion.

Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,600+ biopharma pros reading Endpoints daily — and it's free.

Novartis CEO Vas Narasimhan [via Bloomberg/Getty]

I’m not per­fect: No­var­tis chief Vas Narasimhan al­most apol­o­gizes in the wake of a new cri­sis

Vas Narasimhan has warily stepped up with what might pass as something close to a borderline apology for the latest scandal to engulf Novartis.

But he couldn’t quite get there.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,600+ biopharma pros reading Endpoints daily — and it's free.

FDA to Sarep­ta: Your wide­ly an­tic­i­pat­ed fol­lowup to Ex­ondys 51 is not get­ting an ac­cel­er­at­ed OK for Duchenne MD

In one of the least anticipated moves of the year, the FDA has rejected Sarepta’s application for an accelerated approval of its Duchenne MD drug golodirsen after fretting over safety issues.

In a statement that arrived after the bell on Monday, Sarepta explained the CRL, saying:

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,600+ biopharma pros reading Endpoints daily — and it's free.

Levi Garraway. Broad Institute via Youtube

Roche raids Eli Lil­ly for its next chief med­ical of­fi­cer as San­dra Horn­ing plans to step down

We found out Monday morning where Levi Garraway was headed after he left Eli Lilly as head of oncology R&D a few days ago. Roche named Garraway as their new chief medical officer, replacing Sandra Horning, who they say is retiring from the company.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,600+ biopharma pros reading Endpoints daily — and it's free.

Af­ter a posse of Wall Street an­a­lysts pre­dict a like­ly new win for Sarep­ta, we're down to the wire on a crit­i­cal FDA de­ci­sion

As Bloomberg notes, most of the Wall Street analysts that cover Sarepta $SRPT are an upbeat bunch, ready to cheer on the team when it comes to their Duchenne MD drugs, or offer explanations when an odd setback occurs — as happened recently with a safety signal that was ‘erroneously’ reported last week.

Ritu Baral Cowen
Endpoints News

Basic subscription required

Unlock this story instantly and join 57,600+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: No­var­tis spin­off Nabri­va fi­nal­ly scores its first an­tibi­ot­ic ap­proval

In May, Nabriva Therapeutics suffered a setback after the FDA rejected its antibiotic for complicated urinary tract infections — the Novartis spinoff has now had some better luck with the US agency, which on Monday approved its other drug for community-acquired bacterial pneumonia.

The drug, lefamulin, has been developed as an intravenous and oral formulation and been tested in two late-stage clinical trials. The semi-synthetic compound, whose dosing can be switched between the two formulations, is engineered to inhibit the synthesis of bacterial protein by binding to a part of the bacterial ribosome.

Saqib Islam. CheckRare via YouTube

Spring­Works seeks $115M to push Pfiz­er drugs across fin­ish line while Sat­suma sells mi­graine play in $86M IPO

SpringWorks and Satsuma — both biotech spinouts that have closed B rounds in April — are loading up with IPO cash to boost their respective late-stage plans.
SpringWorks

Bain-backed SpringWorks is the better-known company of the two, and it’s gunning for a larger windfall of $115 million to add to $228 million from previous financings. In the process, the Stamford, CT-based team is also drawing the curtains on the partnerships it has in mind for the pair of assets it had initially licensed from Pfizer.

Mi­nor­i­ty racial groups con­tin­ue to be dis­mal­ly rep­re­sent­ed in can­cer tri­als — study

Data reveal that different racial and ethnic groups — by nature and/or nurture — can respond differently in terms of pharmacokinetics, efficacy, or safety to therapeutics, but this disparity is not necessarily accounted for in clinical trials. A fresh analysis of the last decade of US cancer drug approvals suggests the trend continues, cementing previous research that suggests oncology trials are woefully under-representative of the racial makeup of the real world.

Van­da shares slide af­ter FDA spurns their big end­point and re­jects a pitch on jet lag re­lief

Back in the spring of last year, Vanda Pharmaceuticals $VNDA served up a hot stew of mixed data for a slate of endpoints related to what they called clear evidence that their melatonin sleep drug Hetlioz (tasimelteon) could help millions of travelers suffering from jet lag.

Never mind that they couldn’t get a planned 90 people in the study, settling for 25 instead; Vanda CEO Mihael H. Polymeropoulos said they were building on a body of data to prove it would help jet-lagged patients looking for added sleep benefits. And that, they added, would be worth a major upgrade from the agency as they sought to tackle a big market.