Mer­ck dis­cov­ers 'root cause' of ni­trosamine lev­els in block­buster di­a­betes drugs

Mer­ck has iden­ti­fied what caused lev­els of the ni­trosamine NTTP to ap­pear in batch­es of its block­buster di­a­betes drugs, the com­pa­ny con­firmed on Wednes­day.

An un­named source told Bloomberg, which first re­port­ed the news, that NTTP con­t­a­m­i­na­tion in cer­tain batch­es of its sitagliptin di­a­betes prod­ucts Janu­via and Janu­met oc­curred dur­ing stor­age and man­u­fac­tur­ing process­es.

The FDA said last Au­gust that it be­came aware of a ni­trosamine im­pu­ri­ty in cer­tain sam­ples of Mer­ck’s type 2 di­a­betes drug Janu­via. In or­der to avoid a short­age of the block­buster drug, the agency tem­porar­i­ly al­lowed high­er im­pu­ri­ty lev­els than the ac­cept­able in­take lim­it.

The agency added in a state­ment at the time that giv­en sitagliptin — the drug name for Janu­via — is a pre­scrip­tion drug, “it could be dan­ger­ous for pa­tients” with type 2 di­a­betes to stop tak­ing it with­out talk­ing to their health care pro­fes­sion­al first.

Nor­mal­ly, if a drug con­tains ni­trosamine lev­els above a cer­tain ac­cept­ed dai­ly lim­it, the fed­er­al agency rec­om­mends a re­call.

A Mer­ck spokesper­son told End­points News on Wednes­day that:

Mer­ck has iden­ti­fied the root cause of the ni­trosamine, NTTP, for­ma­tion in cer­tain batch­es of its sitagliptin-con­tain­ing prod­ucts and has sub­mit­ted a de­tailed re­port of its find­ings to rel­e­vant health au­thor­i­ties.

The com­pa­ny has al­ready in­sti­tut­ed ad­di­tion­al qual­i­ty con­trols and ex­pects to be able to con­sis­tent­ly re­duce NTTP lev­els to meet the long-term ac­cept­able dai­ly in­take lev­el this year, al­though the spe­cif­ic time­frame will be based on the progress of tim­ing to in­sti­tute process mod­i­fi­ca­tions and on en­gage­ment with FDA and oth­er Health Au­thor­i­ties.

Ni­trosamine im­pu­ri­ties have im­pact­ed mul­ti­ple com­pa­nies — such as back in 2019, when the FDA found ni­trosamine in drugs like Pfiz­er’s Chan­tix and Ac­cupril, as well as met­formin from mul­ti­ple com­pa­nies.

Ni­trosamines, per the FDA, can in­crease the risk of can­cer if pa­tients are ex­posed above the ac­cept­able lim­its for a long pe­ri­od of time.

More re­cent­ly, Phath­om Phar­ma­ceu­ti­cals had its launch of vono­prazan to treat He­li­cobac­ter py­lori (H. py­lori) bac­te­r­i­al in­fec­tions de­layed af­ter trace lev­els of ni­trosamines were found in com­mer­cial batch­es.

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

Forge Biologics has developed a bespoke affinity chromatography platform approach that factors in unique vector combinations to streamline development timelines and assist our clients in efficiently entering the clinic. By leveraging our experience with natural and novel serotypes and transgene conformations, we are able to accelerate affinity chromatography development by nearly 3-fold. Many downstream purification models are serotype-dependent, demanding unique and time-consuming development strategies for each AAV gene therapy product1. With the increasing demand to propel AAV gene therapies to market, platform purification methods that support commercial-scale manufacturing of high-quality vectors with excellent safety and efficacy profiles are essential.

Luke Miels, GSK chief commercial officer

GSK picks up Scynex­is' FDA-ap­proved an­ti­fun­gal drug for $90M up­front

Editor’s note: This is a live story and will be updated.

GSK is dishing out $90 million cash to add an antifungal drug to its commercial portfolio, in a deal spotlighting the pharma giant’s growing focus on infectious diseases.

The upfront will lock in an exclusive license to Scynexis’ Brexafemme, which was approved in 2021 to treat a yeast infection known as vulvovaginal candidiasis, except in China and certain other countries where Scynexis already out-licensed the drug.

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Feng Zhang (Susan Walsh/AP Images)

In search of new way to de­liv­er gene ed­i­tors, CRISPR pi­o­neer turns to mol­e­c­u­lar sy­ringes

Bug bacteria are ruthless.

Some soil bacteria have evolved tiny, but deadly injection systems that attach to insect cells, perforate them and release toxins inside — killing a bug in just a few days’ time. Scientists, on the other hand, want to leverage that system to deliver medicines.

In a paper published Wednesday in Nature, MIT CRISPR researcher Feng Zhang and his lab describe how they engineered these syringes made by bacteria to deliver potential therapies like toxins that kill cancer cells and gene editors. With the help of an AI program, they developed syringes that can load proteins of their choice and selectively target human cells.

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See­los Ther­a­peu­tics 'tem­porar­i­ly' stops study in rare neu­ro dis­or­der for busi­ness rea­sons

Microcap biotech Seelos Therapeutics is halting enrollment of its study in spinocerebellar ataxia type 3 (also known as Machado-Joseph disease) because of “financial considerations,” and in order to focus on other studies, the company said today, adding that the pause would be temporary.

The study will continue with the patients who have already enrolled, and the data from them will be used to decide whether to continue enrolling others in the future.

Mathai Mammen, FogPharma's next CEO

Math­ai Mam­men hands in J&J's R&D keys to lead Greg Ver­dine’s Fog­Phar­ma 

In the early 1990s, Mathai Mammen was a teaching assistant in Greg Verdine’s Science B46 course at Harvard. In June, the former R&D head at Johnson & Johnson will succeed Verdine as CEO, president and chair of FogPharma, the same month the seven-year-old biotech kickstarts its first clinical trial.

After leading R&D at one of the largest drugmakers in the world, taking the company through more than half a dozen drug approvals in the past few years, not to mention a Covid-19 vaccine race, Mammen departed J&J last month and will take the helm of a Cambridge, MA biotech attempting to go after what Verdine calls the “true emperor of all oncogenes” — beta-catenin.

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CSL CEO Paul McKenzie (L) and CMO Bill Mezzanotte

Q&A: New­ly-mint­ed CSL chief ex­ec­u­tive Paul McKen­zie and chief med­ical of­fi­cer Bill Mez­zan­otte

Paul McKenzie took over as CEO of Australian pharma giant CSL this month, following in the footsteps of long-time CSL vet Paul Perreault.

With an eye on mRNA, and quickly commercializing its new, $3.5 million-per-shot gene therapy for hemophilia B, McKenzie and chief medical officer Bill Mezzanotte answered some questions from Endpoints News this afternoon about where McKenzie is going to take the company and what advances may be coming to market from CSL’s pipeline. Below is a lightly edited transcript.

Boehringer re­ports ro­bust sales led by type 2 di­a­betes and pul­monary drugs, promis­es more to come high­light­ing obe­si­ty

Boehringer Ingelheim reported human pharma sales of €18.5 billion on Wednesday, led by type 2 diabetes and heart failure drug Jardiance and pulmonary fibrosis med Ofev. Jardiance sales reached €5.8 billion, growing 39% year over year, while Ofev took in €3.2 billion, notching its own 20.6% annual jump.

However, Boehringer is also looking ahead with its pipeline, estimating “In the next seven years the company expects about 20 regulatory approvals in human pharma.”

FDA ap­proves Nar­can opi­oid over­dose re­ver­sal spray for over-the-counter sale

The FDA today approved Emergent BioSolutions’ Narcan brand naloxone nasal spray for over-the-counter sales. The nod was expected and comes on the heels of a unanimous 19-0 advisory committee vote in favor of approval last month.

The move to OTC means the opioid overdose reversal agent will now be available on grocery, convenience and gas stations shelves, as well as potentially for purchase online.

J&J bows out of RSV vac­cine race, end­ing PhI­II study and ced­ing to Pfiz­er, GSK

Johnson & Johnson announced Wednesday morning it is ending development of its adult RSV vaccine that was in the middle of a 27,200-patient trial, giving up a big slice of what’s expected to be the next multibillion-dollar pharma market.

The decision came down to the shifting RSV “competitive landscape,” a company spokesperson tells Endpoints News, adding the “breadth of options” was much different than when J&J first started its pivotal study. The spokesperson declined to comment on the Phase III data, saying only the shot is undergoing an “ongoing assessment.”

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