UP­DAT­ED: Ab­b­Vie adds to the Botox war chest with a 12th FDA ap­proval — but com­pe­ti­tion is fast ap­proach­ing

Com­pe­ti­tion is clos­ing in on Ab­b­Vie’s block­buster Botox fran­chise — de­spite the drug­mak­er’s best ef­forts to avoid it. In the mean­time, the Chica­go area drug gi­ant can take some so­lace in a new in­di­ca­tion that will add to the block­buster drug’s war chest.

The FDA on Wednes­day gave Botox the green light to treat de­tru­sor (blad­der mus­cle) over­ac­tiv­i­ty as­so­ci­at­ed with neu­ro­log­i­cal con­di­tions in chil­dren 5 and old­er who were in­tol­er­ant to or didn’t im­prove on an­ti­cholin­er­gic meds, Ab­b­Vie said in a state­ment. Botox is now the first neu­ro­tox­in ap­proved for such use, the drug­mak­er said.

“While al­ways sat­is­fy­ing to bring forth new in­di­ca­tions, it is par­tic­u­lar­ly re­ward­ing when we can help ad­vance care for pe­di­atric pa­tients,” Mitchell Brin, Ab­b­Vie’s se­nior VP and CSO of Botox and neu­ro­tox­ins, said in a state­ment.

Blad­der mus­cle over­ac­tiv­i­ty oc­curs when the spinal cord and blad­der can’t com­mu­ni­cate ef­fec­tive­ly, caus­ing the blad­der mus­cle to in­vol­un­tar­i­ly con­tract. This in­creas­es pres­sure in the blad­der and re­duces blad­der ca­pac­i­ty, which can cause pa­tients to leak urine and suf­fer blad­der and kid­ney dam­age over time. In chil­dren, the most com­mon neu­ro­log­i­cal cause is spina bi­fi­da, though it can al­so be spurred by con­di­tions like trans­verse myelitis and spinal cord in­jury.

“When car­ing for pe­di­atric pa­tients with neu­ro­genic de­tru­sor over­ac­tiv­i­ty, we strive to re­duce blad­der pres­sure and in­crease the blad­der’s ca­pac­i­ty. Pre­vi­ous­ly, treat­ment op­tions were lim­it­ed pri­mar­i­ly to an­ti­cholin­er­gic med­i­cines, where long-term use needs to be con­sid­ered care­ful­ly, in ad­di­tion to surgery,” said Paul Austin, chief of pe­di­atric urol­o­gy at Texas Chil­dren’s Hos­pi­tal and pro­fes­sor of urol­o­gy at Bay­lor Col­lege of Med­i­cine.

Ab­b­Vie sub­mit­ted a sup­ple­men­tal BLA for the con­di­tion back in June, and said it ex­pect­ed a de­ci­sion by Q1 2021. Right on time, the OK was based on a Phase III study with more than 100 chil­dren, which showed that Botox re­duced day­time uri­nary in­con­ti­nence episodes, low­ered max­i­mum blad­der pres­sure and in­creased blad­der ca­pac­i­ty af­ter six weeks.

The most com­mon ad­verse re­ac­tions were bac­teri­uria (20%), uri­nary tract in­fec­tion (7%), leuko­cy­turia (7%), and hema­turia (3%), ac­cord­ing to Ab­b­Vie.

Al­ler­gan snagged its first ap­proval for Botox back in 1989 for two rare eye mus­cle dis­or­ders — ble­pharospasm and stra­bis­mus — then stacked on a va­ri­ety of oth­er in­di­ca­tions, in­clud­ing chron­ic mi­graine, over­ac­tive blad­der, cer­vi­cal dys­to­nia, spas­tic­i­ty and se­vere un­der­arm sweat­ing.

The fran­chise be­came Ab­b­Vie’s in 2019 when it sealed a $63 bil­lion deal to buy out Al­ler­gan. Ab­b­Vie im­me­di­ate­ly carved off Botox’s cos­met­ic use and Al­ler­gans’ oth­er cos­met­ic port­fo­lio in­to an Al­ler­gan Aes­thet­ics sub­sidiary and kept the drug’s ther­a­peu­tic in­di­ca­tions un­der the larg­er com­pa­ny’s di­rect um­brel­la.

Al­ler­gan has put up a tough fight against Botox com­peti­tors, in­clud­ing Evo­lus, which Al­ler­gan took to court on al­le­ga­tions that its Jeu­veau was de­vel­oped us­ing a stolen trade se­cret. In De­cem­ber, Evo­lus was is­sued a 21-month ban on the im­por­ta­tion or sale of the wrin­kle treat­ment — which was re­duced from an ini­tial 10-year ban pro­posed by a judge, Bloomberg re­port­ed. 

Still, oth­er ri­vals are cir­cling in on Botox, in­clud­ing Re­vance, which read out pos­i­tive Phase III re­sults for its Dax­i­bot­u­linum­tox­i­nA in Oc­to­ber. The FDA de­ferred its de­ci­sion on Re­vance’s BLA in No­vem­ber due to Covid-re­lat­ed trav­el re­stric­tions that kept the agency from per­form­ing an in­spec­tion of the com­pa­ny’s man­u­fac­tur­ing fa­cil­i­ty. And In June, Re­vance and My­lan an­nounced plans to move for­ward with a sep­a­rate pro­gram for a Botox biosim­i­lar.

Botox raked in $991.3 mil­lion in net sales in 2019, a 9.3% in­crease from 2018.

This sto­ry has been up­dat­ed to add that the new in­di­ca­tion in­cludes chil­dren who are in­tol­er­ant to an­ti­cholin­er­gic meds. 

MedTech clinical trials require a unique regulatory and study design approach and so engaging a highly experienced CRO to ensure compliance and accurate data across all stages is critical to development milestones.

In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

Avance Clinical is the Australian CRO for international biotechs providing world-class clinical research services with FDA-accepted data across all phases. With Avance Clinical, biotech companies can leverage Australia’s supportive clinical trials environment which includes no IND requirement plus a 43.5% Government incentive rebate on clinical spend. The CRO has been delivering clinical drug development services for international biotechs for FDA and EMA regulatory approval for the past 24 years. The company has been recognized for the past two consecutive years with the prestigious Frost & Sullivan CRO Best Practices Award and a finalist in Informa Pharma’s Best CRO award for 2022.

Mathai Mammen (Rob Tannenbaum, Endpoints News at BIO 2018)

Math­ai Mam­men makes an abrupt ex­it as head of the big R&D group at J&J

In an after-the-bell shocker, J&J announced Monday evening that Mathai Mammen has abruptly exited J&J as head of its top-10 R&D group.

Recruited from Merck five years ago, where the soft-spoken Mammen was being groomed as the successor to Roger Perlmutter, he had been one of the top-paid R&D chiefs in biopharma. His group spent $12 billion last year on drug development, putting it in the top 5 in the industry.

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Illustration: Kim Ryu for Endpoints News

Why non-opi­oid pain drugs keep fail­ing — and what's next for the field

In 1938, Rita Levi-Montalcini was forced to move her lab into her bedroom in Turin, as Mussolini’s facist government expelled Jewish people from studying or working in schools in Italy. Levi-Montalcini, then just a few years out of medical school and using sewing needles as scalpels in her makeshift lab, would soon discover nerve growth factor, or NGF, in chicken embryos.

Her discoveries formed the basis of our understanding of the peripheral nervous system and how cells talk to each other, and Levi-Montalcini went on to win the Nobel Prize in 1986. Much later, NGF was hailed as a promising target for new pain therapies, with some analysts quoting an $11 billion market. However, the latest anti-NGF candidate, Pfizer and Eli Lilly’s tanezumab, was rejected by the FDA last year because of a side effect that dissolved bone in some of its patients.

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Samantha Du, Zai Lab CEO

Any­one still look­ing for a CD47? Zai Lab shelves PhI pro­gram af­ter re­view­ing 'com­pet­i­tive land­scape'

Over the past few years, the promise of blocking CD47 — a “don’t eat me” signal co-opted by cancer cells — has sent drugmakers big and small into a frenzy. But one biotech is now bowing out.

Zai Lab is deprioritizing ZL-1201, its CD47 inhibitor, scrapping plans for a Phase II trial. It will now “pursue out-licensing opportunities,” the company said in its Q2 update. The decision was based on a review of the competitive landscape, it added, without going into further details.

Ted Love, Global Blood Therapeutics CEO

Up­dat­ed: Pfiz­er scoops up Glob­al Blood Ther­a­peu­tics and its sick­le cell ther­a­pies for $5.4B

Pfizer is dropping $5.4 billion to acquire Global Blood Therapeutics.

Just ahead of the weekend, word got out that Pfizer was close to clinching a $5 billion buyout — albeit with other potential buyers still at the table. The pharma giant, flush with cash from Covid-19 vaccine sales, apparently got out on top.

The deal immediately swells Pfizer’s previously tiny sickle cell disease portfolio from just a Phase I program to one with an approved drug, Oxbryta, plus a whole pipeline that, if all approved, the company believes could make for a $3 billion franchise at peak.

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Andy Jassy, Amazon CEO (Isaac Brekken/AP Images for NFL, File)

Up­dat­ed: FDA slaps Ama­zon with a warn­ing let­ter for sell­ing OTC mole re­moval prod­ucts

The FDA’s Center for Drug Evaluation and Research on Tuesday released a warning letter sent last week to Amazon CEO Andy Jassy in Seattle for selling mole removal products over-the-counter, or, as the FDA explains, “introducing, delivering, or causing the introduction or delivery into interstate commerce of products that are unapproved new drugs.”

“There are no over-the-counter (OTC) drugs that can be legally sold for mole or skin tag removal, and FDA has safety concerns about drugs marketed OTC directly to consumers for these uses,” the agency said in its Aug. 4 warning.

FDA commissioner Rob Califf (Tom Williams/CQ Roll Call via AP Images)

With drug pric­ing al­most done, Con­gress looks to wrap up FDA user fee leg­is­la­tion

The Senate won’t return from its summer recess until Sept. 6, but when it does, it officially has 18 business days to finalize the reauthorization of the FDA user fee programs for the next 5 years, or else thousands of drug and biologics reviewers will be laid off and PDUFA dates will vanish in the interim.

FDA commissioner Rob Califf recently sent agency staff a memo explaining how, “Our latest estimates are that we have carryover for PDUFA [Prescription Drug User Fee Act], the user fee funding program that will run out of funding first, to cover only about 5 weeks into the next fiscal year.”

Pascal Soriot, AstraZeneca CEO (David Zorrakino/Europa Press via AP Images)

As­traZeneca and Dai­ichi Sankyo sprint to mar­ket af­ter FDA clears En­her­tu in just two weeks

Regulators didn’t keep AstraZeneca and Daiichi Sankyo waiting long at all for their latest Enhertu approval.

The partners pulled a win on Friday in HER2-low breast cancer patients who’ve already failed on chemotherapy, less than two weeks after its supplemental BLA was accepted. While this isn’t the FDA’s fastest approval — Bristol Myers Squibb won an OK for its blockbuster checkpoint inhibitor Opdivo in just five days back in March — it comes well ahead of Enhertu’s original Q4 PDUFA date.

Civi­ca, Mayo Clin­ic and oth­ers sound off on FDA draft guid­ance to mit­i­gate drug short­ages

Several pharma groups are laying out the positives and negatives of new FDA draft guidance on how best to handle drug shortages.

The draft is intended to help companies develop and implement risk management plans (RMPs) to assist with any shortages of drugs or biologics. The guidance recommends a framework and factors for stakeholders to develop RMPs for their establishments, API manufacturers and others.

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