Mark Foley, Revance CEO

Fol­low­ing CRL, Re­vance says it's clear on in­struc­tions for re­sub­mit­ting BLA

In Oc­to­ber, the FDA hand­ed Re­vance Ther­a­peu­tics a CRL for its botox-based frown line ther­a­py, and the com­pa­ny said that the de­fi­cien­cies stemmed from a man­u­fac­tur­ing site. Now, the com­pa­ny says it has re­ceived the Type A meet­ing min­utes, and clear in­struc­tions for ad­dress­ing the short­com­ings.

Re­vance must pro­duce three con­sec­u­tive drug sub­stance lots and one drug prod­uct lot for Dax­i­bot­u­linum­tox­i­nA for In­jec­tion for glabel­lar lines, in or­der to re­sub­mit its BLA, the com­pa­ny said. This was de­ter­mined in a Dec 15 meet­ing. An­oth­er in­spec­tion of the man­u­fac­tur­ing site in north­ern Cal­i­for­nia will be re­quired af­ter the re­sub­mis­sion. The FDA has up to six months to com­plete the in­spec­tion and re­view.

“We be­lieve we have a clear path to re­sub­mis­sion of the BLA for Dax­i­bot­u­linum­tox­i­nA for In­jec­tion for glabel­lar lines fol­low­ing our Type A meet­ing with the FDA,” CEO Mark Fo­ley said in a state­ment. “As we have not­ed pre­vi­ous­ly and as con­firmed by the FDA dur­ing the meet­ing, the CRL was re­lat­ed to the on­site in­spec­tion of our man­u­fac­tur­ing fa­cil­i­ty and not the safe­ty and ef­fi­ca­cy of our drug prod­uct. The qual­i­fi­ca­tion of our new WCB is in progress and we look for­ward to re­sub­mit­ting the BLA as soon as pos­si­ble.”

Reg­u­la­tors found the Re­vance cell banks test­ing meth­ods — which are done to en­sure the safe­ty and pu­rifi­ca­tion of a prod­uct — were not suf­fi­cient enough to track qual­i­ty, and the man­u­fac­tur­ing process was dif­fer­ent from the one orig­i­nal­ly pro­posed for com­mer­cial­iza­tion, ac­cord­ing to a Form 483. Pro­ce­dures al­so lacked writ­ten de­tails, and the ac­tu­al yield and the­o­ret­i­cal yield didn’t match up, the FDA said.

The BLA was orig­i­nal­ly sub­mit­ted in Jan­u­ary 2020, but a re­view was de­layed be­cause of the Covid-19 pan­dem­ic.

There were no oth­er is­sues raised with the drug, the biotech said. But in­vestors re­act­ed, as shares plum­met­ed more than 30% af­ter the clos­ing bell. That fall has stopped, but not re­cov­ered yet, as shares of $RVNC were still $14.31 short­ly af­ter the open­ing bell.

Though the tri­als did not study the prod­uct against brand-name Botox, the best-sell­ing Al­ler­gan prod­uct gen­er­al­ly lasts for three to four months. Piv­otal Phase III stud­ies showed the treat­ment, dubbed Dax­i­bot­u­linum­tox­i­nA for In­jec­tion, al­lowed adults to main­tain mild frown lines for a me­di­an of 24 weeks with no se­ri­ous side ef­fects. Al­ler­gan’s brand-name Botox is said to last be­tween three and four months.

Even be­fore the CRL, Re­vance had prob­lems with the FDA, thanks to, in part, a back­log on in­spec­tions. The FDA said in No­vem­ber 2020 that it’s “ac­tive­ly work­ing to de­fine an ap­proach for out­stand­ing in­spec­tions,” but was held up due to trav­el re­stric­tions. That’s a prob­lem that hasn’t yet gone away, thanks to the emer­gence of the Omi­cron vari­ant.

Ed­i­tor’s Note: For more news and ex­clu­sive cov­er­age from the man­u­fac­tur­ing beat, sub­scribe to the End­points Man­u­fac­tur­ing week­ly re­port in your read­er pro­file.

Bio­mark­er 'roadmap­s' and the fu­ture of can­cer R&D; Cur­tain rais­es on #AS­CO22; Pfiz­er, No­var­tis tack­le drug ac­cess; 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.

While this was not a week for earth-shattering news, there were certainly a lot of interesting tidbits. If you found this recap helpful, please recommend it to your friends and colleagues. We’ll see you on the other side of the long weekend.

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Keep­ing pres­sure on Am­gen, Mi­rati draws mixed re­views on lat­est cut of KRAS da­ta

As the close runner-up to Amgen’s Lumakras in the KRAS race, any data cut from Mirati’s adagrasib continues to draw scrutiny from analysts. And the latest batch of numbers from ASCO is a decidedly mixed bag.

While a quick comparison suggests that adagrasib spurred slightly more responses and led to a longer overall survival than Lumakras among a group of non-small cell lung cancer patients, its duration of response appears shorter and the safety profile continues to spark concern.

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Switzer­land to de­stroy over 600,000 ex­pired dos­es of Mod­er­na Covid vac­cine

As concerns related to uptake and distribution continue to linger, Switzerland is among the first countries that plans to destroy hundreds of thousands of expired and unused Covid-19 vaccine doses.

The European country said it plans to destroy more than 600,000 doses of Moderna’s Spikevax Covid-19 vaccine as the doses have reached their expiration date.

However, Moderna CEO Stéphane Bancel told the World Economic Forum in Davos, Switzerland that he’s in the process of throwing 30 million doses in the garbage, exclaiming, “We have a big demand problem.”

Man­u­fac­tur­ing roundup: Phar­maron se­cures ac­qui­si­tion of a Rhode Is­land fa­cil­i­ty; GSK to open hub in South Amer­i­ca

A Chinese pharma company is growing its presence in the US with a newly acquired API manufacturing site.

Pharmaron has entered into a definitive agreement to acquire a Coventry, Rhode Island-based API manufacturing site from drug manufacturer Noramco, which was previously owned by Johnson & Johnson and now owned by the private equity firm SK Capital.

According to Pharmaron, the site has an established history of API manufacturing from pilot kilogram to commercial metric ton scales. However, according to The People’s Radio, an NPR station covering Rhode Island and parts of Massachusetts, the facility was formerly owned by a subsidiary of Purdue Pharmaceuticals called Rhodes Technologies and was known for making opioid products. According to that report, because of Purdue’s 2019 bankruptcy filing, the Coventry factory was sold to Noramco, another opioid ingredient manufacturer.

Ann is one of ViiV Healthcare's newest spokespeople as the retired school administrator speaks up about her HIV status.

GSK's Vi­iV de­buts next evo­lu­tion in HIV med Dova­to cam­paign with new spokes­peo­ple and new mes­sage

When Ann saw the first TV commercials for HIV medicine Dovato, she didn’t see herself represented. So the 74-year-old retired school administrator who’s been living with HIV since 1998, reached out to GSK’s ViiV Healthcare and asked why not?

Now Ann is one of three people starring in ViiV’s latest Dovato campaign called “Detect This.” The next-step evolution in the branded campaign plays on the word “detect” — often used in describing HIV status under control as undetectable — but in this case, uses the word as a directive for people to understand they can use fewer medicines.

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Tran­si­tion to new Eu­ro­pean clin­i­cal tri­als in­fo sys­tem starts slow­ly

At the end of January, the European Medicines Agency officially launched its new clinical trials info system (CTIS), although the migration to the new platform has only really just begun, and sponsors have until the end of January 2023 before all initial trial applications must be submitted through CTIS.

Overall, 56 clinical trial applications have been submitted in CTIS during the first 3 months since the launch of the system on Jan. 31, according to new data posted by the EMA. By comparison, about 4,000 new trials are authorized each year across Europe.

Nassim Usman, Catalyst Biosciences CEO

Af­ter $60M Ver­tex deal, group of Cat­a­lyst share­hold­ers claims biotech could’ve sold as­sets three years ago

Catalyst Biosciences was down to five employees in March, and the biotech needed to do something after two rounds of layoffs, a nixed collaboration and a culling of its hemophilia program.

In came Vertex, with $60 million to buy up the South San Francisco biotech’s preclinical complement drugs, which target the system that bridges the body’s innate and adaptive immune response and a class most known for Ultomiris and Soliris. The deal includes CB 2782-PEG, the dry AMD drug that Biogen no longer wanted in March.

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Lina Khan, FTC chair (Graeme Jennings/Pool via AP Images)

Pile-on over PBMs con­tin­ues with FTC com­ments and a new bi­par­ti­san Sen­ate bill

More than 500 stakeholders sent comments to the FTC on whether the commission should look further into pharma middlemen, known as PBMs, with many of the commenters calling for more federal oversight.

Similar to the critical open comment period in a deadlocked FTC session last February, pharmacies and pharmacy groups are continuing to call out the lack of transparency among the top 3 PBMs, which control about 80% of the market.

Pharma brands are losing their shine with US consumers who are now thinking about the economy and inflation instead of Covid. (Credit: Shutterstock)

Phar­ma brands fade in an­nu­al Har­ris con­sumer vis­i­bil­i­ty poll: Mod­er­na drops off and Pfiz­er dips

As Covid-19 concerns are fading in the US, so is biopharma visibility. The annual Axios Harris Poll survey to determine and rank the 100 most top-of-mind brands in the US finds Moderna, which was No. 3 last year, not on the list at all for 2022, and Pfizer sinking 37 spots.

However, it’s not that Moderna or Pfizer did anything wrong, it’s just that Americans have moved on to other worries beyond Covid.

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