Io­n­is, Akcea team face some tough ques­tions on safe­ty as FDA in­sid­ers pon­der risks linked to volane­sors­en

Re­searchers for Io­n­is’ $IONS ma­jor­i­ty-owned spin­out Akcea will have plen­ty of per­suad­ing to do this week if they ever ex­pect to get their drug volane­sors­en on the mar­ket.

The FDA in­ter­nal re­view came out to­day, re­flect­ing the same deep con­cerns that an­a­lysts have ex­pressed about the safe­ty of a drug that has been linked with re­peat­ed in­stances of sud­den and dan­ger­ous drops in platelet counts. Platelets are need­ed to trig­ger the clot­ting that stops bleed­ing.

Akcea’s shares $AK­CA im­me­di­ate­ly tum­bled 15% on the neg­a­tive tone of the in­ter­nal re­view.

James Smith

In a memo to the ad­vi­so­ry com­mit­tee meet­ing on Thurs­day, James Smith, the deputy di­rec­tor of the Di­vi­sion of Me­tab­o­lism and En­docrinol­o­gy Prod­ucts, spot­light­ed a gen­er­al agree­ment that the drug has a clear­ly pos­i­tive ef­fect on reg­u­lat­ing plas­ma triglyc­eride for pa­tients with rare cas­es of fa­mil­ial chy­lomi­crone­mia syn­drome. That’s a sur­ro­gate end­point for the dis­ease.

But is the ben­e­fit re­al­ly worth the risk of bleed­ing? That’s the big ques­tion that the de­vel­op­ers face this week. Reg­u­la­tors are al­so some­what per­plexed by Akcea’s wish to switch the dos­ing reg­i­men and their platelet mon­i­tor­ing strat­e­gy to some­thing that was nev­er test­ed in the clin­i­cal tri­als. 

From Smith’s note:

Al­though the re­views high­light sev­er­al safe­ty/tol­er­a­bil­i­ty is­sues, the pri­ma­ry fo­cus for both the ap­pli­cant and the re­view­ers has been the risk of throm­bo­cy­tope­nia (low blood platelet counts) and re­sult­ing po­ten­tial for se­ri­ous bleed­ing….(S)ome pa­tients can ex­hib­it a rapid and un­pre­dictable re­duc­tion in platelets to ex­treme­ly low lev­els. In CS6, no pa­tients as­signed to place­bo had a platelet count fall be­low 100,000/uL com­pared with 18 (55%) of 33 pa­tients as­signed to volane­sors­en…Switch­ing to bi­week­ly dos­ing and/or dose in­ter­rup­tions have not al­ways led to a suf­fi­cient­ly time­ly re­cov­ery of platelet count; some pa­tients have re­quired treat­ment with pred­nisone, hos­pi­tal­iza­tion, and/or ad­min­is­tra­tion of IVIG. To date, se­ri­ous bleed­ing events have not been ob­served in this rel­a­tive­ly lim­it­ed safe­ty data­base, but the re­view­ers high­light a high­er risk of non-se­ri­ous bleed­ing-re­lat­ed ad­verse events with volane­sors­en (e.g., epis­taxis, pe­techi­ae). Some of these events oc­curred at platelet lev­els where spon­ta­neous bleed­ing would be un­ex­pect­ed, sug­gest­ing the pos­si­bil­i­ty of an ab­nor­mal­i­ty of platelet func­tion as well as an ef­fect on platelet count.

Io­n­is re­port­ed a lit­tle more that a year ago that it had achieved its ef­fi­ca­cy end­point in Phase III. But five pa­tients were forced out of the tri­al due to a threat­en­ing de­cline in platelet counts. Grade 4 throm­bo­cy­tope­nia oc­curred in three pa­tients, which end­ed af­ter they stopped dos­ing. There were no with­drawals due to platelet counts af­ter the com­pa­ny be­gan mon­i­tor­ing the side ef­fect.

If they do get an ap­proval, says Smith, it will have to come with a REMS. But right now, that looks like the best case sce­nario.

Janet Woodcock (Greg Nash/Pool via AP Images)

'I re­al­ly don’t look back': Janet Wood­cock on her tran­si­tion away from drugs

Janet Woodcock may have one of the most historically long and drug-intense tenures in FDA history, but her new role is outside of all things pharma and the once-acting FDA commissioner isn’t looking back.

“No I really don’t look back,” Woodcock told Endpoints News via email on Monday morning. “Yes I will be transitioning. Longer discussion on infrastructure needed.”

Co­pay coupons gone wrong, again: Pfiz­er pays al­most $300K to set­tle com­plaints in four states

Pfizer has agreed to pay $290,000 to settle allegations of questionable copay coupon practices in Arizona, Colorado, Kansas, and Vermont from 2014 to 2018.

While the company has not admitted any wrongdoing as part of the settlement, Pfizer has agreed to issue restitution checks to about 5,000 consumers.

A Pfizer spokesperson said the company has “enhanced its co-pay coupons to alleviate the concerns raised by states and agreed to a $30,000 payment to each.”

Delaware court rules against Gilead and Astel­las in years-long patent case

A judge in Delaware has ruled against Astellas Pharma and Gilead in a long-running patent case over Pfizer-onwed Hospira’s generic version of Lexiscan.

The case kicked off in 2018, after Hospira submitted an Abbreviated New Drug Application (ANDA) for approval to market a generic version of Gilead’s Lexiscan. The drug is used in myocardial perfusion imaging (MPI), a type of nuclear stress test.

Taye Diggs (courtesy Idorsia)

Idor­sia inks an­oth­er celebri­ty en­dors­er deal with ac­tor and dad Taye Dig­gs as Qu­viviq in­som­nia am­bas­sador

Idorsia’s latest Quviviq insomnia campaign details the relatable dad story of a well-known celebrity — actor and Broadway star Taye Diggs.

Diggs stopped sleeping well after the birth of his son, now more than 10 years ago. Switching mom-and-dad nightly shifts to take care of a baby interrupted his sleep patterns and led to insomnia.

“When you’re lucky enough to be living out your dream and doing what you want, but because of something as simple as a lack of sleep, you’re unable to do that, it felt absolutely — it was treacherous,” he says in an interview-style video on the Quviviq website.

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Belén Garijo, Merck KGaA CEO (Kevin Wolf/AP Images for EMD Serono)

Mer­ck KGaA pumps €440M in­to ex­pand­ing and con­struct­ing Irish man­u­fac­tur­ing fa­cil­i­ties

The area of Ireland famous for Blarney Castle and its cliffsides along the Atlantic Ocean is seeing Merck KGaA expand its commitment there.

The German drug manufacturer is expanding its membrane and filtration manufacturing capabilities in Ireland. The company will invest approximately €440 million ($470 million) to increase membrane manufacturing capacity in Carrigtwohill, Ireland, and build a new manufacturing facility at Blarney Business Park, in County Cork, Ireland.

Rep. Katie Porter (D-CA) (Michael Brochstein/Sipa USA/Sipa via AP Images)

House Dems to Sen­ate lead­er­ship: Quick­ly move a rec­on­cil­i­a­tion bill with drug price ne­go­ti­a­tion re­forms

Twenty House Democrats, including Reps. Katie Porter of California and Susan Wild of Pennsylvania, are calling on Senate leaders to move quickly with a reconciliation bill (meaning they only need a simple majority for passage) with prescription drug pricing reforms, and to include adding new authority for Medicare to negotiate drug prices.

They also called on the Senate to specifically follow suit with the House passage of a $35 per month insulin cap (as Senate Majority Leader Chuck Schumer’s deadline for a vote on that provision has come and gone), and to cap Medicare Part D costs at $2,000 per year for seniors.

Phillip Gomez, SIGA CEO

UP­DAT­ED: On the back of SIGA Tech­nolo­gies' win with the FDA, the mon­key­pox virus sees the com­pa­ny spring­ing to fur­ther ac­tion

As the cases of monkeypox now sit at well over 100 worldwide and have spread to multiple continents, the orders for any type of vaccine against monkeypox are seeing nations and medical bodies looking to get their hands on anything and everything. And now SIGA Technologies seems to be getting in on the action.

According to Euronews, SIGA Technologies, a pharmaceutical company that is focused on providing medical countermeasures to biological and chemical attacks, is now in talks with several European authorities looking to stockpile its antiviral that can counter monkeypox. The drug known as tecovirimat or Tpoxx was approved by the FDA in 2018 as a vaccine for smallpox but was approved by the European Medicines Agency to also act against monkeypox, cowpox and complications from immunization with vaccinia.

Lutz Hegemann, Novartis president of global health

No­var­tis li­cens­es out leukemia drug as part of new glob­al coali­tion to in­crease ac­cess to can­cer treat­ments

The Union for International Cancer Control (UICC) has gathered a slate of Big Pharmas for its new collaboration in hopes of increasing access to cancer medicines in lower income countries, UICC announced yesterday.

Dubbed ATOM, or Access to Oncology Medicines, the coalition includes AstraZeneca, BeiGene, Novartis, Bristol Myers Squibb, Roche, Gilead, and Sanofi, among other organizations. The goal of the partnership is to increase generic and biosimilar development of cancer drugs as well as license out essential medicines to these countries. The third part of the partnership includes building up the infrastructure to diagnose cancers and properly handle cancer medicines.

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Bris­tol My­ers dusts off an old Cel­gene chemother­a­py for use in chil­dren with a rare blood can­cer

Bristol Myers Squibb is bringing new life to a chemotherapy drug from the old Celgene pipeline as it touts another approval in a rare form of blood cancer affecting young children.

The FDA on Friday approved Vidaza (chemically known as azacitidine) for pediatric patients 1 month and older with newly diagnosed juvenile myelomonocytic leukemia (JMML). The new indication marks the first approval for Vidaza in more than a decade, though it’s commonly used to treat acute myeloid leukemia and myelodysplastic syndromes (MDS).