Sen. Patty Murray (D-WA) (Graeme Sloan/Sipa USA/Sipa via AP Images)

CDER di­rec­tor on ac­cel­er­at­ed ap­proval re­forms and a court de­ci­sion that will 'send a chill' across rare dis­ease drug de­vel­op­ment

At the sec­ond of two hear­ings be­fore the Sen­ate Health, Ed­u­ca­tion, La­bor & Pen­sions Com­mit­tee on the must-pass leg­is­la­tion (by the end of Sep­tem­ber) re­gard­ing the funds from bio­phar­ma in­dus­try ap­pli­ca­tions that will keep the FDA afloat over the next five years, CDER di­rec­tor Pa­trizia Cavaz­zoni raised par­tic­u­lar con­cerns about a re­cent court de­ci­sion while lay­ing out sev­er­al re­quests for con­gres­sion­al ac­cel­er­at­ed ap­proval re­forms.

Pa­trizia Cavaz­zoni

Re­spond­ing to a ques­tion from Sen. Tam­my Bald­win (D-WI), Cavaz­zoni said she wants to work with Con­gress to find a so­lu­tion af­ter a re­cent court de­ci­sion against the FDA “will send a chill in­to the de­vel­op­ment of rare dis­eases and it will dis­pro­por­tion­ate­ly af­fect chil­dren with rare dis­eases. It’s es­sen­tial to con­tin­ue to gen­er­ate the study of drugs in chil­dren, so this de­ci­sion will re­al­ly go counter to that.”

The case in ques­tion from last Oc­to­ber saw a US ap­peals court over­turn a pri­or FDA court win, say­ing that the agency nev­er should’ve ap­proved a rare dis­ease drug be­cause a pre­vi­ous­ly ap­proved but more ex­pen­sive drug with the same ac­tive in­gre­di­ent has or­phan drug ex­clu­siv­i­ty bar­ring such an ap­proval.

The sit­u­a­tion right now, Cavaz­zoni said, fol­low­ing the court’s de­ci­sion “is a spon­sor could study a dis­ease in a very nar­row seg­ment of the pop­u­la­tion and then be able to block fur­ther ap­provals through­out the en­tire con­di­tion that that drug could ad­dress.”

Sen. Su­san Collins (R-ME) al­so raised ques­tions with Cavaz­zoni re­gard­ing CMS’ re­cent de­ci­sion to not cov­er Bio­gen’s con­tro­ver­sial Alzheimer’s drug, and its dis­cus­sion of the safe­ty of the drug.

Cavaz­zoni de­fend­ed the ap­proval, say­ing the da­ta “are sol­id and the drug is ap­pro­pri­ate­ly made avail­able to pa­tients based on FDA’s de­ci­sion. It’s im­por­tant to dis­tin­guish FDA and CMS’ roles,” she said, adding that FDA is sole­ly re­spon­si­ble for de­ter­min­ing safe­ty and ef­fec­tive­ness, and CMS has a dif­fer­ent stan­dard, rea­son­able and nec­es­sary, which trans­late in­to the set­ting in how the drug is cov­ered.

“There are some ar­eas when it comes to ac­cel­er­at­ed ap­proval where we could use some help from Con­gress,” Cavaz­zoni said, not­ing that FDA doesn’t have the au­thor­i­ty to re­quire that con­fir­ma­to­ry tri­als are start­ed or be un­der­way by the time the drug is ap­proved, or at least have a de­tailed plan to con­duct those tri­als.

“An­oth­er area we can use some help is in ex­pe­dit­ing the with­draw­al of drugs when the con­fir­ma­to­ry tri­als do not con­firm the drug is as­so­ci­at­ed with clin­i­cal ben­e­fit,” Cavaz­zoni said. “Right now the ex­pe­dit­ed with­draw­al path is any­thing but ex­pe­dit­ed. It can take up to 2 years and re­quire lots of re­sources and lots of ad­min­is­tra­tive bur­den.”

Com­mit­tee Chair Sen. Pat­ty Mur­ray of Wash­ing­ton ac­knowl­edged that the user fee pro­grams in gen­er­al have an im­por­tant role, and they en­sure that more drugs and de­vices cross the fin­ish line and that the FDA gets the ap­pro­pri­ate re­sources.

Richard Burr

“It should be un­think­able that af­ter 2 years, when FDA’s work has been more im­por­tant than ever, that we would fail to get this done or force the agency to send pink slips,” Mur­ray said, while say­ing that they should look back at this pan­dem­ic — from FDA’s work to re­view and ap­prove vac­cines quick­ly to oth­er is­sues like test­ing strug­gles and the hy­drox­y­chloro­quine de­ba­cle.

The top Re­pub­li­can mem­ber of the com­mit­tee, Richard Burr of North Car­oli­na, raised con­cerns about the cur­rent lack of funds flow­ing in­to biotech in gen­er­al, and said to­day’s hear­ing was about ac­count­abil­i­ty, while men­tion­ing the need for FDA “to speed not on­ly the re­view of prod­ucts but their de­vel­op­ment as well.”

He al­so raised sev­er­al con­cerns, high­light­ing sev­er­al bench­marks the agency failed to meet in the last user fee agree­ment.

“Now FDA wants dou­ble the mon­ey for mediocre per­for­mance im­prove­ments,” Burr said. “The more you use the user fee process to bul­ly dol­lars out of in­dus­try, hold­ing them hostage, the less ac­count­able the FDA is.”

Pe­ter Marks

CBER di­rec­tor Pe­ter Marks al­so ex­plained the cur­rent sit­u­a­tion of Covid-19 vac­cines for the youngest group of chil­dren (un­der 5), say­ing that as soon as the FDA re­ceives an ap­pli­ca­tion, “we’ll move quick­ly. It’s one of our high­est pri­or­i­ties.”

Again he said that an ad­comm of out­side ex­perts will meet and re­view the da­ta on the vac­cines too, and in the next week, Marks said, the FDA will re­lease a ten­ta­tive time­line for those meet­ing(s) as the agency re­views these 2 ap­pli­ca­tions from Pfiz­er and Mod­er­na. He al­so stressed that the FDA can’t start or fin­ish its re­views un­til the com­plete ap­pli­ca­tions are sub­mit­ted.

Com­pa­nies of­ten re­lease state­ments ahead of the FDA on when such ap­pli­ca­tions are ful­ly sub­mit­ted, he not­ed.

On the top­ic of va­can­cies, which is al­ways a ten­u­ous top­ic at the FDA as sev­er­al se­nior vac­cine and oth­er lead­ers moved on re­cent­ly, Cavaz­zoni said CDER is look­ing to fill roles for about 7-8% of its staff, which “isn’t a high rate for a large or­ga­ni­za­tion,” she said.

In re­sponse to ques­tions over the re­cent­ly un­veiled McK­in­sey con­flicts of in­ter­est with FDA re­gard­ing their opi­oid work, Cavaz­zoni stressed that CDER doesn’t have any con­tracts with McK­in­sey, and while McK­in­sey had worked with FDA, its work with FDA did not en­tail spe­cif­ic sci­en­tif­ic re­views of prod­ucts or process­es.

UP­DAT­ED: In a fresh dis­ap­point­ment, Am­gen spot­lights a ma­jor safe­ty is­sue with KRAS com­bo

Amgen had hoped that its latest study matching its landmark KRAS G12C drug Lumakras with checkpoint inhibitors would open up its treatment horizons and expand its commercial potential. Instead, the combo spurred safety issues that blunted efficacy and forced the pharma giant to alter course on its treatment strategy, once again disappointing analysts who have been tracking the drug’s faltering sales and limited therapeutic reach.

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Ad­dress­ing the ‘Ca­pac­i­ty Crunch’ with a Scal­able Plat­form Process Ap­proach

The field of gene therapy has been diligently moving forward over the past several decades to bring potentially life-saving treatments to patients with genetic diseases. In addition to two approved adeno-associated viral (AAV) gene therapies, there are more than 250 AAV gene therapies in various clinical trial stages.1 AAV vectors remain the most frequently used vector for delivering therapeutic transgenes to target tissues due to their demonstrated and lasting clinical efficacy and extensive safety track record. As AAV therapies advance through clinical trials and into commercialization, many biotech companies are turning to contract development and manufacturing organizations (CDMOs) to prepare their programs for late-stage clinical and commercial scale manufacturing. Given the scope and scale of the manufacturing needs that will accompany regulatory approvals for these assets, CDMOs continue to expand their capacity to meet the needs of increasing prevalent patient populations. However, despite rapid growth, projected gene therapy manufacturing demands still outpace the collective capacity of the CDMO industry.

A $5B Pfiz­er buy­out? Am­gen, Gilead head­line M&A Thurs­day; Al­ny­lam's AT­TR sweep; An­drew Lo's rare dis­ease quest; 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.

One of the cool things about adding EndpointsPharma to the daily roster is that my colleagues can now dedicate time to tracking quarterly updates and tuning into calls with Big Pharma companies. Check out their dispatch from the Q2 earnings below.

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Albert Bourla, Pfizer CEO (Laurent Gillieron/Keystone via AP)

Break­ing: Pfiz­er in hot pur­suit of a $5B buy­out of Glob­al Blood Ther­a­peu­tics — re­port

Pfizer CEO Albert Bourla has vowed to leave no stone unturned in the search for new biotech deals, and the BD team is not letting him down.

The Wall Street Journal reported today that Pfizer is in the final stages of acquiring Global Blood Therapeutics for $5 billion. According to the Journal report, though, Pfizer is not the only buyer at the deal table and while the pharma giant may be close to clinching it, there are no guarantees it will continue.

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Bob Bradway, Amgen CEO (Justin Kase Conder/AP Images for Amgen)

UP­DAT­ED: Am­gen chief Brad­way nabs a rare dis­ease play­er in $4B buy­out as the M&A tem­po ac­cel­er­ates

Amgen CEO Bob Bradway is bellying up to the M&A table today, scooping up the newly anointed commercial biotech ChemoCentryx $CCXI and its recently approved rare disease drug for $3.7 billion out of the cash stockpile. The deal comes in at $52 a share — a hefty increase over the $24.11 close yesterday.

Bradway and the Amgen team get a drug called Tavneos (avacopan) in the deal, a complement factor C5a inhibitor OK’d to treat anti-neutrophil cytoplasmic autoantibody (ANCA)-vasculitis, an autoimmune disease which can be lethal.

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George Yancopoulos, Regeneron president and CSO (Brendan McDermid/Reuters/Alamy)

George Yan­copou­los says he's on the trail of the holy grail: ‘This could rep­re­sent the next break­through for im­munother­a­py’

Two of the most outspoken — and successful — drug developers in biotech say they’ve collected early-stage clinical data that are pointing them down the trail to the holy grail in cancer immunotherapy R&D.

While analysts largely busied themselves today with chronicling the ongoing success of Regeneron’s two big cash cows — Dupixent and Eylea — chief scientist George Yancopoulos and CEO Len Schleifer used the Q2 call to spotlight their early success with a combination of the “homegrown” PSMAxCD28 costimulatory bispecific antibody REGN5678 in combination with their PD-1 checkpoint Libtayo. The presentation comes just weeks after Regeneron completed a deal to gather all rights to the PD-1 that had been in Sanofi’s hands. And the two top execs are unstinting in their praise of the potential of a whole set of costimulatory pipeline projects which they say may finally deliver the long-awaited next-level approach to broadening the immunotherapy field of drugs.

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Sen. Kyrsten Sinema (D-AZ) (Tom Williams/CQ Roll Call via AP Images)

De­moc­rats se­cure sup­port from key sen­a­tor ahead of po­ten­tial drug pric­ing vote

Senate Democrats may have all the votes they need to pass major drug pricing reform, after Sen. Kyrsten Sinema (D-AZ) reportedly pledged her support on Thursday — but will they fit it in before recess?

Sinema said she has agreed to “move forward” with the reconciliation bill with some stipulations, including the removal of a carried tax provision, according to recent reports. The bill is still expected to reduce the deficit by $300 billion, and Sen. Chuck Schumer (D-NY) said that he now anticipates “support from the entire Senate Democratic conference,” the Washington Post reported. 

CDC, NIH, FDA lead­ers call for US-based clin­i­cal tri­al of small­pox drug in treat­ing mon­key­pox

With the rising number of monkeypox cases, leading researchers at the CDC, FDA and NIH are calling on a randomized clinical trial to see if an approved smallpox drug is effective at treating monkeypox.

No monkeypox treatments are approved in the US, so patients looking to get relief for their lesions and other symptoms from the virus must go through a set of hurdles to get the smallpox drug through a government expanded access program. Approved for smallpox in 2018, the drug is marketed as TPOXX by the biotech SIGA. The European Union approved it for monkeypox in addition to smallpox earlier this year and the UK followed suit in July.

CDER director Patrizia Cavazzoni, FDA commissioner Robert Califf and OPDP acting director Catherine Gray

Drug pro­mo­tion en­force­ment so far sim­i­lar un­der new FDA chief, with just 4 let­ters in first half of 2022

Will a trio of new bosses at the FDA lead to an increase in drug advertising enforcement? It’s a good question, but with few letters sent out so far, there’s just not enough information to tell, says one longtime FDA regulatory watchdog.

“I don’t think there is anything to indicate the Administration is leaning one way or another,” Mark Senak, a lawyer at FleishmanHillard who tracks FDA actions on his Eye on FDA blog, said in an email. “It is worth noting that we have a new FDA Commissioner, new head of CDER and a new head of OPDP which opens up the possibility of change, but there has not yet been enough enforcement activity to identify real change.”

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