‘Clin­i­cal su­pe­ri­or­i­ty’: di­azepam nasal spray il­lus­trates FDA pa­ra­me­ters for or­phan drug ex­clu­siv­i­ty

Thanks to the last user fee agree­ment, known as the FDA Reau­tho­riza­tion Act of 2017, the agency can now ex­plain why a new­ly ap­proved or­phan drug is clin­i­cal­ly su­pe­ri­or to pre­vi­ous­ly ap­proved or­phan drugs and there­fore should be award­ed sev­en years of or­phan drug ex­clu­siv­i­ty.

Since 2017, the FDA has on­ly ex­plained how five treat­ments can be con­sid­ered clin­i­cal­ly su­pe­ri­or, with the lat­est com­ing last Fri­day for Neurelis Phar­ma­ceu­ti­cals’ Val­to­co (di­azepam nasal spray). The FDA ex­plains how di­azepam was pre­vi­ous­ly ap­proved as a gel ad­min­is­tered rec­tal­ly where­as Val­to­co’s in­tranasal route of ad­min­is­tra­tion is eas­i­er to use.

“In the con­text of when this drug is to be giv­en, typ­i­cal­ly in the mid­dle of a seizure event, it is in­her­ent­ly eas­i­er to ad­min­is­ter the drug to a pa­tient in­tranasal­ly than rec­tal­ly,” the FDA said.

The four oth­er drugs to ob­tain such clin­i­cal su­pe­ri­or­i­ty find­ings and win the or­phan ex­clu­siv­i­ty from the FDA since 2017 in­clude:

  • Pfiz­er’s My­lotarg (gem­tuzum­ab ozogam­icin) in Sep­tem­ber 2017, af­ter it was ini­tial­ly with­drawn from the mar­ket fol­low­ing an ac­cel­er­at­ed ap­proval in 2000, but was ap­proved lat­er for a low­er dose and dif­fer­ent sched­ule that was found to have less ear­ly mor­tal­i­ty, less he­pa­to­tox­i­c­i­ty, less veno-oc­clu­sive dis­ease, more rapid platelet re­cov­ery and less he­m­or­rhage, the FDA said.
  • CSL Behring’s Hizen­tra (Im­mune Glob­u­lin Sub­cu­ta­neous (Hu­man), 20% Liq­uid) in March 2018 be­cause the pre­vi­ous­ly ap­proved in­tra­venous for­mu­la­tion re­quires a cen­tral ve­nous ac­cess de­vice, which is as­so­ci­at­ed with an in­creased risk of throm­boem­bol­ic events and ac­cess-as­so­ci­at­ed in­fec­tions.
  • Astel­las Phar­ma’s Pro­graf (tacrolimus gran­ules for oral sus­pen­sion) in May 2018 be­cause “tacrolimus gran­ules for oral sus­pen­sion pro­vides an age ap­pro­pri­ate for­mu­la­tion for pe­di­atric pa­tients that avoids the se­vere risks as­so­ci­at­ed with er­ro­neous­ly com­pound­ed tacrolimus,” the FDA said.
  • No­var­tis’ Sig­ni­for LAR (pasireotide) in June 2018 for the treat­ment of Cush­ing’s dis­ease be­cause FDA said the dos­ing reg­i­men of the long-act­ing re­lease (once month­ly) pro­vides a ma­jor con­tri­bu­tion to pa­tient care over the dos­ing reg­i­men of the pre­vi­ous, im­me­di­ate re­lease (twice-dai­ly) ver­sion.

Mov­ing for­ward, drug de­vel­op­ers look­ing to ob­tain this “clin­i­cal­ly su­pe­ri­or” tag for their or­phan prod­ucts should look to 21 CFR 316.3(b)(3), which de­fines how a drug can pro­vide a sig­nif­i­cant ther­a­peu­tic ad­van­tage over an al­ready ap­proved drug (that is oth­er­wise the same drug) in one or more of the fol­low­ing three ways:

“(i) Greater ef­fec­tive­ness than an ap­proved drug (as as­sessed by ef­fect on a clin­i­cal­ly mean­ing­ful end­point in ad­e­quate and well con­trolled clin­i­cal tri­als). Gen­er­al­ly, this would rep­re­sent the same kind of ev­i­dence need­ed to sup­port a com­par­a­tive ef­fec­tive­ness claim for two dif­fer­ent drugs; in most cas­es, di­rect com­par­a­tive clin­i­cal tri­als would be nec­es­sary; or

(ii) Greater safe­ty in a sub­stan­tial por­tion of the tar­get pop­u­la­tions, for ex­am­ple, by the elim­i­na­tion of an in­gre­di­ent or con­t­a­m­i­nant that is as­so­ci­at­ed with rel­a­tive­ly fre­quent ad­verse ef­fects. In some cas­es, di­rect com­par­a­tive clin­i­cal tri­als will be nec­es­sary; or

(iii) In un­usu­al cas­es, where nei­ther greater safe­ty nor greater ef­fec­tive­ness has been shown, a demon­stra­tion that the drug oth­er­wise makes a ma­jor con­tri­bu­tion to pa­tient care.”

For more on the de­ter­mi­na­tions, the FDA pub­lish­es sum­maries of the clin­i­cal su­pe­ri­or­i­ty find­ings when a drug is el­i­gi­ble for or­phan drug ex­clu­siv­i­ty. The FDA Law Blog al­so of­fers more in­for­ma­tion on some of the su­pe­ri­or­i­ty de­ter­mi­na­tions be­fore 2017.

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.

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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Gilead re­leas­es an­oth­er round of murky remde­sivir re­sults

A month after the NIH declared the first trial on remdesivir in Covid-19 a success, Gilead is out with new results on their antiviral. But although the study met one of its primary endpoints, the data are likely to only add to a growing debate over how effective the drug actually is.

In a Phase III trial, patients given a 5-day dose of remdesivir were 65% more likely to show “clinical improvement” compared to an arm given standard-of-care. The trial, though, gave little indication for whether the drug had an impact on key endpoints such as survival or time-to-recovery. And in a surprising twist, a 10-day dosing arm of remdesivir didn’t lead to a statistically significant improvement over standard of care.

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Novus Ther­a­peu­tics plunges deep in­to pen­ny stock ter­ri­to­ry af­ter failed ear tri­al

After a more than 15-year run, a California-based biotech is exploring options, including a sale, after its lead experimental therapy failed an exploratory mid-stage study in patients with middle ear infections characterized by a build-up of fluid behind the eardrum.

The company, initially called Tokai Pharmaceuticals but which subsequently changed its name to Novus Therapeutics in 2017, saw its shares more than halve on Monday after the drug — OP0201— did not pass muster as an adjunct therapy to oral antibiotics in infants and children aged 6 to 24 months with acute otitis media (OM).

Fangliang Zhang (Imaginechina via AP Images)

The big mon­ey: Poised to make drug R&D his­to­ry, a Chi­na biotech un­veils uni­corn rac­ing am­bi­tions in a bid to raise $350M-plus on Nas­daq

Almost exactly three years after Shanghai-based Legend came out of nowhere to steal the show at ASCO with jaw-dropping data on their BCMA-targeted CAR-T for multiple myeloma, the little player with Big Pharma connections is taking a giant step toward making it big on Wall Street. And this time they want to seal the deal on a global rep after staking out a unicorn valuation in what’s turned out to be a bull market for biotech IPOs — in the middle of a pandemic.

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Len Schleifer (left) and George Yancopoulos, Regeneron (Vimeo)

Eyes on he­mo­phil­ia prize, Re­gen­eron adds a $100M wa­ger on joint de­vel­op­ment cam­paign with In­tel­lia

When George Yancopoulos first signed up Intellia to be its CRISPR/Cas9 partner on gene editing projects 4 years ago, the upstart smartly ramped up its IPO at the same time. Today, Regeneron $REGN is coming back in, adding $100 million in an upfront fee and equity to significantly boot up a whole roster of new development projects.

And they’re highlighting some clinical hemophilia research plans in the process.

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Hill­house re­casts spot­light on Chi­na's biotech scene with $160M round for Shang­hai-based an­ti­body mak­er

Almost two years after first buying into Genor Biopharma’s pipeline of cancer and autoimmune therapies, Hillhouse Capital has led a $160 million cash injection to push the late-stage assets over the finish line while continuing to fund both internal R&D and dealmaking.

The Series B has landed right around the time Genor would have listed on the Hong Kong stock exchange, according to plans reported by Bloomberg late last year. Insiders had said that the company was looking to raise about $200 million.

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Jean-Jacques Bienaimé, BioMarin chairman and CEO

Bio­Marin holds the line on bleeds with 4-year val­rox up­date on he­mo­phil­ia A — but what's this about an­oth­er de­cline in Fac­tor 8 lev­els?

BioMarin has posted some top-line results for their 4-year followup on the most advanced gene therapy for hemophilia A — extending its streak on keeping a handful of patients free of bleeds and off Factor VIII therapy, but likely stirring fresh worries over a continued drop in Factor VIII levels.

We just don’t know how big a drop.

We’ll see more data when the results are presented at the World Federation of Hemophilia in a couple of weeks. But in a statement out Sunday night, BioMarin $BMRN reported that none of the patients required Factor VIII treatment, adding:

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As­traZeneca trum­pets the 'mo­men­tous' da­ta they found for Tagris­so in an ad­ju­vant set­ting for NSCLC — but many of the ex­perts aren’t cheer­ing along

AstraZeneca is rolling out the big guns this evening to provide a salute to their ADAURA data on Tagrisso at ASCO.

Cancer R&D chief José Baselga calls the disease-free survival data for their drug in an adjuvant setting of early stage, epidermal growth factor receptor-mutated NSCLC patients following surgery “momentous.” Roy Herbst, the principal investigator out of Yale, calls it “transformative.”

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