In a come­back, Por­to­la scores FDA ac­cel­er­at­ed ap­proval for once-re­ject­ed An­dexxa

Some­how stay­ing on the good side of the FDA, Por­to­la $PT­LA has scored an elu­sive reg­u­la­to­ry win for their once-re­ject­ed drug an­dex­anet al­fa.

The an­ti-an­ti­co­ag­u­lant — to be mar­ket­ed as An­dexxa — won the OK via the ac­cel­er­at­ed ap­proval path­way, mean­ing that Por­to­la will have to run a post-mar­ket­ing tri­al to demon­strate an abil­i­ty to con­trol bleed­ing in pa­tients.  The ap­proval was based on da­ta from two Phase III stud­ies, con­duct­ed among healthy vol­un­teers, that showed An­dexxa could re­verse an­ti­co­ag­u­lant ac­tiv­i­ty of the Fac­tor Xa in­hibitors Xarel­to (ri­varox­a­ban) and Eliquis (apix­a­ban). The drug al­so comes with a black box warn­ing and is in­di­cat­ed for use when re­ver­sal of an­ti­co­ag­u­la­tion is need­ed due to life-threat­en­ing or un­con­trolled bleed­ing.

Bill Lis

Por­to­la has fought long and hard for this win. It first sub­mit­ted an NDA for An­dexxa late 2015, on­ly to be caught off guard with an FDA re­jec­tion. At the time, the South San Fran­cis­co biotech said the agency was look­ing for more in­for­ma­tion on man­u­fac­tur­ing and how the an­ti­dote works in oth­er blood thin­ning drugs, such as edox­a­ban (Savaysa) and enoxa­parin (Lovenox).

The team filed again in Au­gust 2017, ex­act­ly a year af­ter it got the com­plete re­sponse let­ter. Reg­u­la­tors have since pushed back the ac­tion date from Feb­ru­ary to May 4, and Por­to­la hint­ed in a re­cent earn­ings call that there could be fur­ther de­lays as the FDA re­quest­ed fur­ther da­ta, send­ing stock down. But noth­ing came out of that warn­ing, and Por­to­la spread word about the OK late Thurs­day — right be­fore the orig­i­nal ac­tion date.

A spokesper­son told me that the CRL Por­to­la re­ceived in 2016 “fo­cused al­most sole­ly on man­u­fac­tur­ing con­cerns, which Por­to­la ad­dressed.”

“An­dexxa is a break­through prod­uct, and as such, clin­i­cal was much faster than man­u­fac­tur­ing,” they wrote. “In oth­er words, at that time, man­u­fac­tur­ing had to catch up with clin­i­cal.”

In a lengthy press re­lease, Por­to­la did not elab­o­rate on how it re­solved the FDA’s pre­vi­ous con­cerns, choos­ing in­stead to high­light the mar­ket po­ten­tial of its re­ver­sal agent in an era when Fac­tor Xa in­hibitors have be­come in­creas­ing pop­u­lar. One of them is Por­to­la’s own Bevyxxa, whose ap­proval raised some eye­brows since it bare­ly failed a piv­otal tri­al. Eu­ro­pean reg­u­la­tors gave it a thumbs down.

“We are proud that An­dexxa is a first-in-class med­i­cine dis­cov­ered in our labs,” said CEO Bill Lis. “We re­main com­mit­ted to our sci­en­tif­ic lead­er­ship in the fields of throm­bo­sis and hema­to­log­ic can­cers.”

The com­pa­ny now plans to launch an ear­ly sup­ply pro­gram of “Gen­er­a­tion 1” An­dexxa in June, with broad­er com­mer­cial launch an­tic­i­pat­ed in ear­ly 2019, as­sum­ing the FDA green­lights the man­u­fac­tur­ing process of its Gen­er­a­tion 2 prod­uct.

Mean­while, the post-mar­ket­ing tri­al is slat­ed to be­gin in 2019 and be re­port­ed in 2023.

Por­to­la shares edged up 3% in pre-mar­ket trad­ing. Ac­cord­ing to Eval­u­atePhar­maAn­dexxa car­ries a 2022 sell­side rev­enue fore­cast of $749m.

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Roivant par­lays a $450M chunk of eq­ui­ty in biotech buy­out, grab­bing a com­pu­ta­tion­al group to dri­ve dis­cov­ery work

New Roivant CEO Matt Gline has crafted an all-equity upfront deal to buy out a Boston-based biotech that has been toiling for several years now at building a supercomputing-based computational platform to design new drugs. And he’s adding it to the Erector set of science operations that are being built up to support their network of biotech subsidiaries with an eye to growing the pipeline in a play to create a new kind of pharma company.

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Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

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Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Doug Ingram (file photo)

Why not? Sarep­ta’s third Duchenne MD drug sails to ac­cel­er­at­ed ap­proval

Sarepta may be running into some trouble with its next-gen gene therapy approach to Duchenne muscular dystrophy. But when it comes to antisense oligonucleotides, the well-trodden regulatory path is still leading straight to an accelerated approval for casimersen, now christened Amondys 45.

We just have to wait until 2024 to find out if it works.

Amondys 45’s approval was unceremonious, compared to its two older siblings. There was no controversy within the FDA over approving a drug based on a biomarker rather than clinical benefit, setting up a powerful precedent that still haunts acting FDA commissioner Janet Woodcock as biotech insiders weighed her potential permanent appointment; no drama like the FDA issuing a stunning rejection only to reverse its decision and hand out an OK four months later, which got more complicated after the scathing complete response letter was published; no anxious tea leaf reading or heated arguments from drug developers and patient advocates who were tired of having corticosteroids as their loved ones’ only (sometimes expensive) option.

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Mark Mal­lon charts post-Iron­wood course by tak­ing CEO job at NeoGe­nomics; Glax­o­SmithK­line vet Feng Ren joins In­sil­i­co as CSO

Mark Mallon steps aside at Ironwood on March 12 after close to two years at the helm, and he already has a new change of scenery squared away. Beginning April 19, Mallon takes charge as CEO of cancer-focused genetic test maker NeoGenomics out of Fort Myers, FL while his predecessor, Douglas VanOort, is retiring after 12 years as NeoGenomics’ chairman and CEO.

It’s a fresh start for Mallon after what will amount to a tumultuous 23 months as Ironwood’s chief executive. Last year was marked by trial failures that spelled double trouble, leaving the Ironwood cupboard bare: first, a Linzess reformulation for irritable bowel syndrome with diarrhea (IBS-D) in May, and then the drug IW-3718 for persistent acid reflux in September. After IW-3718’s discontinuation, Ironwood chopped its staff by 35%. On Feb. 8, Mallon announced his departure at Ironwood, with president Tom McCourt getting bumped up to interim CEO.

Covid-19 roundup: Mer­ck­'s $356M sup­ply deal on hold as FDA asks for more da­ta; FDA ap­proves Pfiz­er/BioN­Tech vac­cine stor­age at stan­dard freez­er temps

Merck is pushing back plans to supply the US government with a Covid-19 drug after the FDA asked for more data to support an emergency use authorization.

The antibody, MK-7110, had looked promising in a Phase III study conducted by OncoImmune before Merck came along and bought the biotech for $425 million. At the interim analysis, investigators looked at data from 203 patients and concluded that a single dose of the drug cut the risk of death or respiratory failure by more than 50% among severe patients. And those taking the drug had a 60% higher chance of improvement in clinical status compared to placebo.

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Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

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S&P ex­pects steady ero­sion in Big Phar­ma's cred­it pro­file in 2021 as new M&A deals roll in — but don't un­der­es­ti­mate their un­der­ly­ing strength

S&P Global has taken a look at the dominant forces shaping the pharma market and come to the conclusion that there will be more downgrades than upgrades in 2021 — the 8th straight year of steady decline.

But it’s not all bad news. Some things are looking up, and there’s still plenty of money to be made in an industry that enjoys a 30% to 40% profit margin, once you factor in steep R&D expenses.