UP­DAT­ED: FDA pan­dem­ic de­lays strike again with Is­raeli mi­cro­cap the lat­est to re­ceive a CRL based on in­spec­tion set­backs

Is­raeli mi­cro­cap Pro­tal­ix Ther­a­peu­tics and its part­ners at Ital­ian phar­ma com­pa­ny Chiesi re­ceived bad news re­gard­ing their Fab­ry dis­ease pro­gram.

The FDA is­sued the pair a com­plete re­sponse let­ter for the can­di­date, known as pe­gu­ni­gal­si­dase al­fa, the com­pa­nies said Wednes­day. Reg­u­la­tors were un­able to con­duct an in­spec­tion of a man­u­fac­tur­ing site in Is­rael due to Covid-19 trav­el re­stric­tions, lead­ing to the re­jec­tion, ac­cord­ing to Pro­tal­ix.

No con­cerns were raised over the safe­ty and ef­fi­ca­cy of the drug can­di­date, Pro­tal­ix added.

Dror Bashan

“While dis­ap­point­ing, we re­main con­fi­dent in the strength of our da­ta and in the depth of our pro­gram,” said Pro­tal­ix CEO Dror Bashan in a state­ment. “We re­main com­mit­ted to the pro­gram and to work­ing with the FDA and Chiesi to­ward the ap­proval of PRX‑102.”

Pro­tal­ix joins a grow­ing num­ber of phar­ma com­pa­nies that have said their FDA pitch­es were scut­tled pri­mar­i­ly as a re­sult of the pan­dem­ic, with reg­u­la­tors un­able to com­plete in­spec­tions in time for the re­view process. Pe­gu­ni­gal­si­dase al­fa had been sub­mit­ted un­der the ac­cel­er­at­ed ap­proval path­way and had al­ready seen its PDU­FA pushed back from Jan­u­ary.

On May 7, the FDA reached out to End­points News to clar­i­fy that, as a gen­er­al rule, “the lack of an in­spec­tion alone is not a rea­son for a com­plete re­sponse let­ter.”

The re­stric­tions have hit both large phar­mas and small biotechs, from No­var­tis, Mallinck­rodt and Bris­tol My­ers Squibb to North Car­oli­na-based Liq­uidia Tech­nolo­gies and now Pro­tal­ix. Even in the face of ex­pect­ed OKs, like with No­var­tis’ in­clisir­an, the FDA has strug­gled to con­duct time­ly in­spec­tions and in­stead been forced to pri­or­i­tize the re­view.

Gen­er­al­ly, the new sys­tem has been more friend­ly to those with new mol­e­cules with high­er clin­i­cal needs. And sim­i­lar to Pro­tal­ix’s case, the agency did not con­duct an on­site in­spec­tion at all for in­clisir­an, No­var­tis said at the time of its CRL.

An­oth­er wrin­kle in the Pro­tal­ix re­jec­tion comes from the re­cent full ap­proval of Sanofi Gen­zyme’s Fab­razyme, long the stan­dard of care in Fab­ry dis­ease. When Pro­tal­ix re­sub­mits its pitch fol­low­ing a Type A meet­ing, any sub­mis­sion will have to be in the con­text of that ap­proval, the CRL re­port­ed­ly said.

Giv­en that both Fab­razyme and pe­gu­ni­gal­si­dase al­fa are en­zyme re­place­ment ther­a­pies, that could hint to­ward the high­er con­cen­tra­tion the Pro­tal­ix can­di­date showed in its Phase III tri­al. Back when the first re­sults came in June 2019, high lev­els of pe­gu­ni­gal­si­dase al­fa cir­cu­lat­ed in the blood­stream af­ter 28 days, with a mean con­cen­tra­tion of 138 ng/mL among 15 evalu­able pa­tients.

In con­trast, Fab­razyme had his­tor­i­cal­ly shown a mean con­cen­tra­tion of 20 ng/mL at 10 hours post in­fu­sion.

More re­cent­ly though, Pro­tal­ix has os­ten­si­bly been work­ing to show it can prove bet­ter than Fab­razyme. This past Feb­ru­ary, the com­pa­ny re­leased topline re­sults from a small Phase III study where pa­tients would switch over from Fab­razyme to their ex­per­i­men­tal drug, show­ing that an IV in­fu­sion of pe­gu­ni­gal­si­dase al­fa every four weeks was well-tol­er­at­ed with no pa­tients de­vel­op­ing an­ti-drug an­ti­bod­ies.

Fab­ry dis­ease is a rare ge­net­ic dis­or­der that pre­vents the body from mak­ing the al­pha-Galac­tosi­dase-A en­zyme, re­sult­ing in ab­nor­mal de­posits of fat­ty sub­stances in blood ves­sel walls. The ul­ti­mate con­se­quences of these de­posits can range from pain and im­paired pe­riph­er­al sen­sa­tion to kid­ney and heart fail­ure.

May 7 up­date: This ar­ti­cle has been up­dat­ed to in­clude the FDA’s clar­i­fi­ca­tion that the lack of an in­spec­tion alone is not the rea­son for a CRL.

So­cial: from Pro­tal­ix web­site

Mov­ing Out of the Clin­ic with Dig­i­tal Tools: Mo­bile Spirom­e­try Dur­ing COVID-19 & Be­yond

An important technology in assessing lung function, spirometry offers crucial data for the diagnosis and monitoring of pulmonary system diseases, as well as the ongoing measurement of treatment efficacy. But trends in the healthcare industry and new challenges introduced by the COVID-19 pandemic are causing professionals in clinical practice and research to reevaluate spirometry’s deployment methods and best practices.

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Sanofi, Glax­o­SmithK­line jump back in­to the PhI­II race for a Covid vac­cine — as the win­ners con­gre­gate be­hind the fin­ish line

Sanofi got out early in the race to develop a vaccine using more of a traditional approach, then derailed late last year as their candidate failed to work in older people. Now, after likely missing the bus for the bulk of the world’s affluent nations, they’re back from that embarrassing collapse with a second attempt using GSK’s adjuvant that may get them back on track — with a potential Q4 launch that the rest of the world will be paying close attention to.

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SCO­TUS de­clines to re­view En­brel biosim­i­lar case, tee­ing up 30+ years of ex­clu­siv­i­ty and $20B more for Am­gen’s block­buster

As the House Oversight Committee is set to grill AbbVie CEO Richard Gonzalez on Tuesday over tactics to block competition for its best-selling drug of all time, another decision on Capitol Hill on Monday opened the door for billions more in Amgen profits over the next eight years.

The Supreme Court on Monday denied Novartis subsidiary Sandoz’s petition to review a Federal Circuit’s July 2020 decision concerning its biosimilar Erelzi (etanercept-szzs), which FDA approved in 2016 as a biosimilar to Amgen’s Enbrel (etanercept). Samsung’s Enbrel biosimilar Eticovo also won approval in 2019 and remains sidelined.

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How to man­u­fac­ture Covid-19 vac­cines with­out the help of J&J, Pfiz­er or Mod­er­na? Bi­ol­yse sees the dif­fi­cul­ties up close

When Biolyse, an Ontario-based manufacturer of sterile injectables, forged a deal with Bolivia last week to manufacture up to 50 million J&J Covid-19 vaccine doses, the agreement kicked off what will prove to be a test case for how difficult the system of compulsory licenses is to navigate.

The first problem: When Biolyse asked J&J, via a March letter, to license its Covid-19 vaccine, manufacture it in Canada and pay 5% royalties on shipments to needy, low-income countries, J&J rejected the offer, refusing to negotiate. J&J also did not respond to a request for comment.

Tim Mayleben (L) and Sheldon Koenig (Esperion)

On the heels of a sting­ing Q1 set­back, Es­pe­ri­on's long­time cham­pi­on is ex­it­ing the helm and turn­ing the wheel over to a mar­ket­ing pro

Just days after getting stung by criticism from a badly disappointed group of analysts, there’s a big change happening today at the helm of Esperion $ESPR.

Longtime CEO Tim Mayleben, who championed the company for 9 years from early clinical through a lengthy late-stage drive to successfully get their cholesterol drug approved for a significant niche of patients in the US, is out of the C suite, effective immediately. Sheldon Koenig — hired at the end of 2020 with a resume replete with Big Pharma CV sales experience —  is stepping into his place, promising to right a badly listing commercial ship that’s been battered by market forces.

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No­var­tis' En­tresto takes its 2nd fail­ure of the week­end at ACC, show­ing no ben­e­fit in most dire heart fail­ure pa­tients

Novartis’ Entresto started the ACC weekend off rough with a trial flop in heart attack patients, slowing the drug’s push into earlier patients. Now, an NIH-sponsored study is casting doubt on Entresto’s use in the most severe heart failure patients, another black mark on the increasingly controversial drug’s record.

Entresto, a combination of sacubitril and valsartan, could not beat out valsartan alone in an outcomes head-to-head for severe heart failure patients with a reduced ejection fraction (HFrEF), according to data presented Monday at the virtual American College of Cardiology meeting.

Matt Gline (L) and Vivek Ramaswamy

In­sid­er ac­count of Roivan­t's SPAC deal — and that $7.3B val­u­a­tion — re­veals a few se­crets as Matt Gline po­si­tions the com­pa­ny as the new ‘Big Phar­ma’

It was Oct. 7, 2020, and Matt Gline wasn’t wasting any time.

The CEO of Roivant had word that KKR vet Jim Momtazee’s SPAC had priced late the night before, triggering a green light for anyone interested in pursuing a big check for future operations and riding the financial instrument to Nasdaq. So he wrote a quick email congratulating Momtazee, whom he knew, for the launch.

Oh, and maybe Momtazee would like to schedule something with Gline and his executive chairman, Roivant founder Vivek Ramaswamy, to chat about Roivant and its business?

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$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

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John­son & John­son do­nates Ebo­la vac­cine amid new out­break; Ji Xing promis­es more than $127M for Mile­stone's nasal spray for rapid heart rate

As Johnson & Johnson continues to roll out its Covid-19 shot, the company is also focused on another vaccine.

J&J is donating up to 200,000 doses of its Ebola vaccine regimen developed with Bavarian Nordic to help health authorities deal with a new outbreak in Sierra Leone. The regimen, Zabdeno and Mvabea, was granted prequalification by the WHO in April, which will help accelerate its registration in countries where Ebola is a threat.