Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since los­ing a con­tro­ver­sial court case over or­phan drug ex­clu­siv­i­ty last year, the FDA’s Of­fice of Or­phan Prod­ucts De­vel­op­ment has re­mained en­tire­ly silent on or­phan ex­clu­siv­i­ty for any prod­uct ap­proved since last No­vem­ber, leav­ing many spon­sors in lim­bo on what to ex­pect.

That si­lence means that for more than 70 or­phan-des­ig­nat­ed in­di­ca­tions for more than 60 prod­ucts, OOPD has is­sued no pub­lic de­ter­mi­na­tion on the sev­en-year or­phan ex­clu­siv­i­ty in the Or­ange Book, and no new list­ings of or­phan ex­clu­siv­i­ty ap­pear in OOPD’s search­able data­base, as high­light­ed re­cent­ly by George O’Brien, a part­ner in May­er Brown’s Wash­ing­ton, DC of­fice.

“These spon­sors can­not even be cer­tain that their or­phan-des­ig­nat­ed prod­ucts will be pro­tect­ed by or­phan ex­clu­siv­i­ty, be­cause FDA’s OOPD has ef­fec­tive­ly stopped mak­ing ex­clu­siv­i­ty de­ter­mi­na­tions since late 2021. The agency ap­pears to be seek­ing to avoid hav­ing to rec­og­nize an or­phan ex­clu­siv­i­ty broad­er than a prod­uct’s ap­proved use, as the Cat­a­lyst de­ci­sion would seem to re­quire of FDA,” O’Brien wrote yes­ter­day.

The FDA said in an emailed state­ment that FDA “is not cur­rent­ly fi­nal­iz­ing ODE [or­phan drug ex­clu­siv­i­ty] de­ter­mi­na­tions” be­cause of the “far-reach­ing im­pli­ca­tions” of the court’s de­ci­sion. The agency added:

The de­ci­sion has caused un­cer­tain­ty for rare dis­ease drug de­vel­op­ment. Un­der the court’s in­ter­pre­ta­tion of the scope of ODE, ODE would block ap­proval of an­oth­er com­pa­ny’s ap­pli­ca­tion for the same drug for the en­tire dis­ease or con­di­tion for which the drug is grant­ed or­phan-drug des­ig­na­tion, re­gard­less of whether the drug was ap­proved on­ly for a nar­row­er use or in­di­ca­tion.  Un­der that in­ter­pre­ta­tion, a spon­sor could seek ap­proval and ex­clu­siv­i­ty for a drug by fo­cus­ing on the small­est, eas­i­est-to-study pop­u­la­tions and such ex­clu­siv­i­ty would block the drug for the en­tire dis­ease, even though the spon­sor did not in­vest in study­ing and de­vel­op­ing the drug for all in­di­vid­u­als with the dis­ease. This could ad­verse­ly af­fect chil­dren—par­tic­u­lar­ly the youngest pe­di­atric pop­u­la­tions—and oth­er pop­u­la­tions that are typ­i­cal­ly stud­ied lat­er in drug de­vel­op­ment.

What’s unique about this sit­u­a­tion, O’Brien told End­points News in a phone in­ter­view, is that any con­gres­sion­al fix would have to be retroac­tive. And if there isn’t a con­gres­sion­al fix in the near term, “this is re­al­ly go­ing to snow­ball and force FDA’s hand” as any sec­ond-in-line com­peti­tors for a nov­el prod­uct could seek ap­proval for a dif­fer­ent sub­set of the same dis­ease, es­sen­tial­ly di­vid­ing up the dis­ease and win­ning ex­clu­siv­i­ty for all sub­sets if Cat­a­lyst re­mains the law.

“It’s pret­ty un­usu­al for FDA to try to un-ring the bell, and go back to re­cod­i­fy an in­ter­pre­ta­tion,” O’Brien added.

The agency made clear last May that the court’s de­ci­sion would have a pro­found im­pact on rare dis­ease drug de­vel­op­ment and in the way it as­sess­es ex­clu­siv­i­ty as it “blocks ap­proval of an­oth­er com­pa­ny’s ap­pli­ca­tion for the same drug for the en­tire dis­ease or con­di­tion for which the drug is grant­ed or­phan-drug des­ig­na­tion, re­gard­less of whether the drug was ap­proved on­ly for a nar­row­er use or in­di­ca­tion.”

The agency even went so far as to lob­by Con­gress on the is­sue, seek­ing a per­ma­nent res­o­lu­tion, but to no avail yet.

Or­phan ex­clu­siv­i­ty is grant­ed to drugs des­ig­nat­ed and ap­proved to treat dis­eases or con­di­tions af­fect­ing few­er than 200,000 peo­ple in the US (or more than 200,000 and no hope of re­cov­er­ing costs).

O’Brien said his phar­ma clients are con­fi­dent that if an ap­proval is a first-ever ap­proval, the ex­clu­siv­i­ty will be there down the road, but there are “still some frus­tra­tions” par­tic­u­lar­ly as the In­fla­tion Re­duc­tion Act ex­empts drugs from Medicare ne­go­ti­a­tions if they have on­ly one or­phan in­di­ca­tion, so some spon­sors may al­so be wor­ried about los­ing that ex­emp­tion.

He al­so said he thought FDA could grant the ex­clu­siv­i­ty and put the dates down in its data­base be­cause Cat­a­lyst “is about scope of ex­clu­siv­i­ty, not el­i­gi­bil­i­ty for earn­ing it.”

The Cat­a­lyst 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.

Af­ter ask­ing the Supreme Court to re­view the case, the two com­pa­nies an­nounced a set­tle­ment in Ju­ly, where­by Ja­cobus agreed to with­draw its pe­ti­tion to SCO­TUS and Cat­a­lyst dis­missed its patent in­fringe­ment claims and ac­quired rights to dis­trib­ute Ja­cobus’ Ruzur­gi in the US as a treat­ment for the rare Lam­bert-Eaton myas­thenic syn­drome in pe­di­atric pa­tients.

“As a re­sult, the out­come that FDA ap­pears to have sought to avoid — a sin­gle ap­proved am­i­fam­pri­dine prod­uct on the mar­ket — re­mains the sta­tus quo, at least un­til the ex­pi­ra­tion of the sev­en-year or­phan ex­clu­siv­i­ty pe­ri­od for Cat­a­lyst’s Fir­dapse in No­vem­ber 2025,” O’Brien wrote.

In the com­ing months, Con­gress will ei­ther need to pass a long-term fix for all or­phan in­di­ca­tions, or the FDA will need to fi­nal­ly con­sid­er how the court’s flip af­fects drugs with ac­tive terms of or­phan drug ex­clu­siv­i­ty as well as cur­rent­ly mar­ket­ed drugs, in­clud­ing gener­ics.

The FDA pre­vi­ous­ly said it ex­pects that some drugs that are in late-stage de­vel­op­ment, or that have al­ready been sub­mit­ted for mar­ket­ing ap­pli­ca­tion re­view, would be blocked from ap­proval un­der the Cat­a­lyst de­ci­sion’s in­ter­pre­ta­tion of the Or­phan Drug Act.

“The agency could al­so con­sid­er open­ing a pub­lic dock­et to so­lic­it stake­hold­er feed­back on pro­posed res­o­lu­tions, should a leg­isla­tive fix not ar­rive soon,” O’Brien wrote, adding:

In the mean­time, we rec­om­mend that spon­sors care­ful­ly as­sess whether a com­peti­tor is like­ly to seek ap­proval for the in­di­ca­tion or use whose or­phan ex­clu­siv­i­ty has not yet been rec­og­nized by FDA. In that sit­u­a­tion, con­sid­er­a­tion should be giv­en to a more as­sertive ap­proach, in­clud­ing pe­ti­tion­ing FDA to award the or­phan ex­clu­siv­i­ty or prepar­ing for po­ten­tial lit­i­ga­tion pri­or to a com­peti­tor ap­proval.

Syn­log­ic pres­i­dent and CEO Aoife Bren­nan re­ceived an or­phan drug des­ig­na­tion to­day for its po­ten­tial treat­ment of ho­mo­cystin­uria, a rare meta­bol­ic dis­ease, telling End­points via email:

The Or­phan Drug Des­ig­na­tion makes a re­al and crit­i­cal dif­fer­ence for life sci­ences com­pa­nies – es­pe­cial­ly de­vel­op­ment stage com­pa­nies – at­tempt­ing to tack­le se­ri­ous med­ical needs that af­fect small­er pop­u­la­tions. With Or­phan Drug Des­ig­na­tion the op­por­tu­ni­ties for more open di­a­logue with the FDA dur­ing the de­vel­op­ment and reg­is­tra­tion process, tax ben­e­fits and fee waivers are ma­te­r­i­al and can af­fect in­vest­ment de­ci­sions in ar­eas of sig­nif­i­cant med­ical need. We sup­port any ac­tions that will con­tin­ue to bring ac­cess to Or­phan Drug des­ig­na­tion for el­i­gi­ble com­pa­nies to help them ad­vance pro­grams.

Ed­i­tor’s note: Ar­ti­cle up­dat­ed with com­ment from the FDA.

Trodelvy notch­es a win in most com­mon form of breast can­cer

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

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Teresa Graham, incoming Roche Pharmaceuticals CEO

In­com­ing Roche CEO builds out his top team, tap­ping Genen­tech vet to lead phar­ma di­vi­sion

Roche announced another leadership shuffle Thursday morning – the head of global product strategy, Teresa Graham, will take over as CEO of Roche Pharmaceuticals in March while the company’s corporate executive committee will make a spot for Levi Garraway, CMO and executive VP of global product development.

Thomas Schinecker will take over the top spot as Roche group CEO in March, leaving his spot as head of diagnostics.

FDA ap­proves GSK's ane­mia drug with safe­ty warn­ing — af­ter bat­ting back sim­i­lar drugs

GSK has secured the first of four US approvals it’s hoping for this year, as the FDA greenlit daprodustat as a treatment for anemia due to chronic kidney disease.

But the FDA limited the use of the drug, to be marketed as Jesduvroq, to patients who have been receiving dialysis for at least four months and stopped short of approving it for patients not dependent on dialysis — in line with the recommendations of the advisory committee it consulted.

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David Kirn, 4D Molecular Therapeutics CEO (via website)

FDA places hold on 4D Mol­e­c­u­lar’s Fab­ry gene ther­a­py

4D Molecular Therapeutics quietly tucked an FDA clinical hold on its Fabry gene therapy into an SEC filing.

Meanwhile, the biotech issued a press release the same day after the closing bell on Thursday touting an IND for another asset, in diabetic macular edema.

The California biotech had paused enrollment of patients in its two trials of the Fabry gene therapy (4D-310) last month after three patients experienced kidney issues, all of which were resolved within four weeks. At the time, 4DMT said it would wait until the second half of this year to look at 12-month clinical data on six patients in the Phase I/II trials, one in the US and one in Taiwan and Australia.

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Raymond Stevens, Structure Therapeutics CEO

Be­hind Fri­day's $161M IPO: A star sci­en­tist, GPCR drug dis­cov­ery and a plan to chal­lenge phar­ma in di­a­betes

What does it take to pull off a $161 million biotech IPO these days?

In Structure Therapeutics’ case, it means having a star scientist co-founder paired with the computational drug discovery company Schrödinger, $198 million in private funding from blue-chip investors, almost six years of research work on G protein-coupled receptors and a slate of oral, small-molecule drugs, with an eye on the huge and growing diabetes and weight-loss market.

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Af­ter 13 years, Ramy Mah­moud steps in­to CEO seat at Opti­nose; Ru­pert Vessey set to ex­it Bris­tol My­ers in Ju­ly

After 13 years as president and COO at Optinose, Ramy Mahmoud has stepped into a new role as its CEO. He is taking the place of Peter Miller, who stepped down earlier this week, though Miller is still staying with the company as a consultant.

In 2010, the two business partners joined Optinose to take it in a new direction, transforming it from a delivery platform to product company. They previously worked together at Johnson & Johnson, when Miller was president at Janssen and Mahmoud headed medical affairs. Miller said after he learned about Optinose, “I did what I always do, which is find people smarter than me to talk with about the idea. And the first person I called was Ramy … and I said, ‘Hey, Ramy, what do you think of this technology?’”

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Te­va drops out of in­dus­try trade group PhRMA

Following in AbbVie’s footsteps, Teva confirmed on Friday that it’s dropping out of the industry trade group Pharmaceutical Research and Manufacturers of America (PhRMA).

Teva didn’t give a reason for its decision to leave, saying only in a statement to Endpoints News that it annually reviews “effectiveness and value of engagements, consultants and memberships to ensure our investments are properly seated.”

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Sanofi CFO Jean-Baptiste de Chatillon (L) and CEO Paul Hudson (Romuald Meigneux/Sipa via AP Images)

Sanofi sees downtick in flu sales as it preps for launch of RSV an­ti­body

Sanofi expects its RSV antibody jointly developed with AstraZeneca will be available next season, executive VP of vaccines Thomas Triomphe announced on the company’s quarterly call.

Beyfortus, also known as nirsevimab, was approved in the EU back in November and is currently under FDA review with an expected decision coming in the third quarter of this year. The news comes as the FDA plans to hold advisory committee meetings over the next couple months to review RSV vaccines from Pfizer and GSK.