A decade af­ter it first failed, a Shire-de­vel­oped Take­da an­tivi­ral ap­pears suc­cess­ful in Phase III

Near­ly 20 years af­ter it first en­tered the clin­ic and over a decade af­ter it first flunked a Phase III tri­al, a Take­da-owned drug to treat CMV in­fec­tions has proven ef­fec­tive in a late-stage study.

Take­da didn’t break down all the num­bers, but said that in a 352-per­son tri­al, marib­avir out­per­formed physi­cian’s choice in clear­ing in­fec­tions in trans­plant pa­tients who were re­sis­tant to cur­rent treat­ments. In a state­ment, Obi Umeh, Take­da’s marib­avir pro­gram leader, said they would take the da­ta to reg­u­la­tors in the US and Eu­rope.

CMV, or cy­tomegalovirus, is a com­mon virus that af­fects much of the pop­u­la­tion with­out caus­ing symp­toms, but it can be dan­ger­ous to peo­ple whose im­mune sys­tems are com­pro­mised, such as re­cip­i­ents of bone mar­row or or­gan trans­plants.

Obi Umeh

“To­day, trans­plant pa­tients who do not re­spond or ex­pe­ri­ence ad­verse events re­lat­ed to ex­ist­ing ther­a­pies may be at high­er risk for com­pli­ca­tions from the virus, in­clud­ing trans­plant fail­ure and death,” Umeh said. “Marib­avir has the po­ten­tial to re­de­fine man­age­ment of post-trans­plant CMV in­fec­tions by help­ing pa­tients clear the virus with less treat­ment lim­it­ing tox­i­c­i­ties.”

An ap­proval would give Take­da one of the first big wins from the Shire buy­out and mark the cul­mi­na­tion of a wild, two-decade ride for a drug Glax­o­SmithK­line first syn­the­sized two decades ago. In 2003, af­ter some ear­ly work in the clin­ic, the then an­tivi­ral-fo­cused Big Phar­ma li­censed the drug to the rare dis­ease and in­fec­tious dis­ease-fo­cused biotech Vi­roPhar­ma.

Vi­roPhar­ma ad­vanced the drug, with pos­i­tive re­sults, through Phase II, but in 2009, it missed the pri­ma­ry end­point on a Phase III study, fail­ing to pre­vent CMV in­fec­tions bet­ter than place­bo in pa­tients re­ceiv­ing bone mar­row trans­plants. Vi­roPhar­ma went back to the draw­ing board, even­tu­al­ly ar­gu­ing that a high­er dosage might lead to a bet­ter re­sponse.

In 2013, though, the drug left Vi­roPhar­ma’s hands and passed to Shire, which bought out the en­tire biotech for $4.2 bil­lion. The Irish drug­mak­er upped the dosage and ran the drug through a smat­ter­ing of phar­ma­co­ki­net­ic and ef­fi­ca­cy stud­ies, test­ing whether giv­ing 4 to 12 times the amount of drug might im­prove per­for­mance.

In 2016, they showed ef­fi­ca­cy in a Phase II study that 400mg, 800mg, and 1200mg helped clear in­fec­tion. Based off those re­sults, the FDA hand­ed the com­pa­ny break­through des­ig­na­tion. The most re­cent Phase III used 400 mg, or four times the dosage of the Phase III that failed in 2009.

The same year it re­ceived break­through des­ig­na­tion, the com­pound served as one of the as­sets in Take­da’s de­ci­sion to buy out Shire for $62 bil­lion. Glob­al­Da­ta pro­ject­ed that it could earn around $200 mil­lion per year in sales by 2023.

Still, key ques­tions re­main for the drug. Take­da has yet to break down the safe­ty da­ta, which ap­peared to be a con­cern in a re­cent Phase II study. Last year, the com­pa­ny an­nounced re­sults from a tri­al com­par­ing marib­avir to the Roche an­tivi­ral Val­cyte. Marib­avir was bet­ter at clear­ing in­fec­tion, but Val­cyte ap­peared safer: Two thirds of the marib­avir group saw treat­ment-re­lat­ed ad­verse events, com­pared to one fifth of Val­cyte pa­tients.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

All about Omi­cron; We need more Covid an­tivi­rals; GSK snags Pfiz­er’s vac­cine ex­ec; Janet Wood­cock’s fu­ture at FDA; and more

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Pfiz­er, Am­gen and Janssen seek fur­ther clar­i­ty on FDA's new ben­e­fit-risk guid­ance

Three top biopharma companies are seeking more details from the FDA on how the agency conducts its benefit-risk assessments for new drugs and biologics.

While Pfizer, Amgen and Janssen praised the agency for further spelling out its thinking on the subject in a new draft guidance, including a discussion of patient experience data as part of the assessment, the companies said the FDA could’ve included more specifics in the 20-page draft document.

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Usama Malik

Ex-Im­munomedics CFO charged with in­sid­er trad­ing, faces up to 20 years in prison af­ter al­leged­ly tip­ping off girl­friend and rel­a­tives of a PhI­II suc­cess

The former CFO of Immunomedics, who helped steer the company to its $21 billion buyout by Gilead last year, has been charged with insider trading, the Department of Justice announced Thursday.

Usama Malik tipped off his then-girlfriend and four others that a Phase III study for Trodelvy would be stopped early four days before Immunomedics publicly announced the result in April 2020, DoJ alleged in its complaint. The individuals then purchased Immunomedics shares, selling them after the news broke and Immunomedics’ stock price doubled.

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Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

As Omi­cron spread looms, oral an­tivi­rals ap­pear to be one of the best de­fens­es — now we just need more

After South African scientists reported a new Covid-19 variant — dubbed Omicron by the WHO — scientists became concerned about how effective vaccines and monoclonal antibodies might be against it, which has more than 30 mutations in the spike protein.

“I think it is super worrisome,” Dartmouth professor and Adagio co-founder and CEO Tillman Gerngross told Endpoints News this weekend. Moderna CEO Stéphane Bancel echoed similar concerns, telling the Financial Times that experts warned him, “This is not going to be good.”

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Ab­b­Vie tacks on a new warn­ing to Rin­voq la­bel as safe­ty frets crimp JAK class

The safety problems that continue to plague the JAK class as new data highlight some severe side effects are casting a large shadow over AbbVie’s Rinvoq.

As a result of a recent readout highlighting major adverse cardiac events (MACE), malignancy, mortality and thrombosis with Xeljanz a couple of months ago, AbbVie put out a notice late Friday afternoon that it is adding the new class risks to its label for their rival drug.

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Biospec­i­men M&A: Dis­cov­ery ac­quires Al­bert Li's he­pa­to­cyte project; PhI­II tri­al on Bay­er's Nube­qa reached pri­ma­ry end­point

Discovery Life Sciences has acquired what claims to be the Maryland-based host of the world’s largest hepatocyte inventory, known as IVAL, to help researchers select more effective and safer drug candidates in the future.

The combined companies will now serve a wider range of drug research and development scientists, according to Albert Li, who founded IVAL in 2004 and is set to join the Discovery leadership team as the CSO of pharmacology and toxicology.

Re­searchers move clos­er to de­ci­pher­ing blood clots from As­traZeneca, J&J's Covid-19 vac­cines

Researchers may be nearing an answer for the mysterious and life-threatening blood clots that appeared on very rare occasions in people who received the J&J or AstraZeneca Covid-19 vaccine.

The new work builds on an early hypothesis researchers in Norway put forward last spring, when the cases first cropped up. They proposed the events were similar to blood clots that can occur in a small subset of patients who receive heparin, one of the most commonly used blood thinners.

Ed Kaye, Stoke Therapeutics CEO

Stoke touts ear­ly signs of ef­fi­ca­cy for Dravet syn­drome drug

Two and a half years after driving his antisense oligonucleotide platform to Wall Street, Stoke Therapeutics CEO Ed Kaye is painting a fuller picture of the company’s first clinical data. And though the trial wasn’t powered to detect statistical significance, Kaye says the readout shows early signs of efficacy in kids with a rare, drug-resistant form of epilepsy

STK-001 was well-tolerated in single and multiple doses in 22 Dravet syndrome patients between the ages of 2 and 18 years old, Stoke announced on Friday. What’s more, 12 of the 17 evaluable patients at the time (70.6%) saw reductions from baseline in convulsive seizure frequency, according to the company.