UP­DAT­ED: Take­da suc­ceeds where oth­er phar­mas have failed with PhI­II win for cy­tomegalovirus castoff marib­avir

Marib­avir, once a tri­al dud and mul­ti­ple-time castoff, re­ceived new life from the FDA right be­fore Take­da picked up Shire in 2019. Now, Take­da is post­ing win­ning late-stage da­ta from the drug that could help it suc­ceed where so many oth­ers have failed.

In a 352-per­son tri­al com­par­ing marib­avir to physi­cian’s choice an­tivi­rals, more than twice as many pa­tients on marib­avir achieved CMV viremia clear­ance at eight weeks — the study’s pri­ma­ry end­point, ac­cord­ing to Take­da. Of the 235 pa­tients who re­ceived marib­avir, 131 (or 55.7%) achieved clear­ance ver­sus 28 of 117 (or 23.9%) of those on con­ven­tion­al an­tivi­ral ther­a­pies (p<0.001). Viremia is the iso­la­tion of CMV by cul­ture.

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

Vol­un­teers in Take­da’s open-la­bel tri­al, dubbed SOL­STICE, ran­dom­ly re­ceived ei­ther marib­avir, or one or a com­bi­na­tion of com­mon­ly used an­tivi­ral ther­a­pies like gan­ci­clovir, val­gan­ci­clovir, fos­car­net or cid­o­fovir. The par­tic­i­pants, who were hematopoi­et­ic cell trans­plant and sol­id or­gan trans­plant re­cip­i­ents, were treat­ed for eight weeks, then fol­lowed for an­oth­er 12.

Break­ing it down fur­ther, Take­da said 55.6% of sol­id or­gan trans­plant pa­tients on marib­avir saw CMV viremia clear­ance at week eight, com­pared with 26.1% of those on oth­er ther­a­pies. And of the hematopoi­et­ic cell trans­plant pa­tients, 55.9% achieved clear­ance at week eight com­pared to 20.8% on oth­er drugs.

In ad­di­tion to the pri­ma­ry end­point, Take­da says it met a key sec­ondary end­point: im­prove­ment in the clear­ance of CMV viremia and as­so­ci­at­ed symp­tom con­trol through four months And those who took marib­avir showed a low­er in­ci­dence of treat­ment-re­lat­ed tox­i­c­i­ties com­mon with oth­er an­tivi­rals, ac­cord­ing to the com­pa­ny.

Treat­ment-re­lat­ed se­ri­ous ad­verse events led to the deaths of one pa­tient in each treat­ment group, ac­cord­ing to Take­da, though it’s un­clear what caused the deaths. As of press time, the com­pa­ny de­clined to pro­vide more in­for­ma­tion.

Take­da of­fered a first glimpse at the Phase III re­sults back in De­cem­ber, and an­nounced that it would take the da­ta to reg­u­la­tors in the US and Eu­rope. In an emailed state­ment, Take­da said it plans to file with the FDA in the first half of FY 2021.

An ap­proval would be a sweet end to marib­avir’s wild-two-decade ride. Glax­o­SmithK­line first syn­the­sized the drug 20 years ago and did some ear­ly clin­i­cal work, be­fore li­cens­ing it to the rare dis­ease and in­fec­tious dis­ease-fo­cused biotech Vi­roPhar­ma.

Vi­roPhar­ma suc­cess­ful­ly took it through Phase II, then missed the pri­ma­ry end­point in a Phase III study in 2009. Marib­avir failed to pre­vent CMV in­fec­tions bet­ter than place­bo in pa­tients re­ceiv­ing bone mar­row trans­plants. Vi­roPhar­ma sug­gest­ed a high­er dose might lead to a bet­ter re­sponse — but end­ed up pass­ing the can­di­date to Shire dur­ing a $4.2 bil­lion buy­out in 2013.

Shire ran with Vi­roPhar­ma’s idea, giv­ing 4 to 12 times more drug in var­i­ous phar­ma­co­ki­net­ic and ef­fi­ca­cy stud­ies. They got the re­sults they were look­ing for in 2016, prov­ing in a Phase II study that 400mg, 800mg, and 1200mg helped clear in­fec­tion. The FDA com­mend­ed the re­sults with a break­through des­ig­na­tion in 2018. And the fol­low­ing year, Take­da com­plet­ed its ac­qui­si­tion of Shire for $62 bil­lion.

Marib­avir has come a long way in­deed, but it’s not over the goal line just yet.

MedTech clinical trials require a unique regulatory and study design approach and so engaging a highly experienced CRO to ensure compliance and accurate data across all stages is critical to development milestones.

In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

Avance Clinical is the Australian CRO for international biotechs providing world-class clinical research services with FDA-accepted data across all phases. With Avance Clinical, biotech companies can leverage Australia’s supportive clinical trials environment which includes no IND requirement plus a 43.5% Government incentive rebate on clinical spend. The CRO has been delivering clinical drug development services for international biotechs for FDA and EMA regulatory approval for the past 24 years. The company has been recognized for the past two consecutive years with the prestigious Frost & Sullivan CRO Best Practices Award and a finalist in Informa Pharma’s Best CRO award for 2022.

Tony Coles, Cerevel CEO

Cerev­el takes the pub­lic of­fer­ing route, with a twist — rais­ing big mon­ey thanks to ri­val da­ta

As public biotechs seek to climb out of the bear market, a popular strategy to raise cash has been through public offerings on the heels of positive data. But one proposed raise Wednesday appeared to take advantage not of a company’s own data, but those from a competitor.

Cerevel Therapeutics plans to raise $250 million in a public offering and another $250 million in debt, the biotech announced Wednesday afternoon, even though it did not report any news on its pipeline. However, the move comes days after rival Karuna Therapeutics touted positive Phase III data in schizophrenia, a field where Cerevel is pursuing a similar program.

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Who are the women blaz­ing trails in bio­phar­ma R&D? Nom­i­nate them for End­points' 2022 spe­cial re­port

Over the past three years, Endpoints News has spotlighted 60 women who have blazed trails and supercharged R&D across the biopharma world. And judging from the response we’ve received, to both our special reports and live events, telling their stories — including any obstacles they may have had to overcome — has inspired our readers in many different ways.

But change takes time, and the fact remains that women are still underrepresented at the upper ranks of the drug-making world.

Bernat Olle, Vedanta Biosciences CEO

Cit­ing 'chal­leng­ing eco­nom­ic en­vi­ron­ment,' PhI­II-ready mi­cro­bio­me biotech lays off 20% of staffers

The market downturn isn’t just sweeping up public biotechs.

Vedanta Biosciences, a developer of oral drugs derived from the human microbiome, is laying off about 20% of its staff — an unfortunately common occurrence these days. But CEO Bernat Olle took the unusual step of sharing the decision on LinkedIn and offering to connect the employees being let go with any company that’s hiring in their areas.

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Up­dat­ed: Amid mas­sive re­struc­tur­ing, Bio­gen looks to re­duce phys­i­cal pres­ence in Boston

Biogen is putting a sizable chunk of office and research space in Kendall Square and Weston, MA up for sublease, marking another big change as the biotech grapples with the aftershock of a disastrous and controversial rollout for its Alzheimer’s drug.

The subbleases are “part of Biogen’s overall implementation of the ‘Future of Work,’ which is allowing us to optimize our footprint and reduce the amount of space we occupy, taking into consideration new elements such as the hybrid work model,” Biogen spokesperson Ashleigh Koss wrote in a statement to Endpoints News, adding that the company has had subleases across several buildings for years.

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Saurabh Saha, Centessa CEO (BIO19)

One of 2021's star biotech play­ers flags an­oth­er big set­back for the pipeline

Two months after scuttling their lead drug, Centessa’s executive team is back with the latest in a series of setbacks that have tanked its stock and blown holes in its strategic lineup of biotech subs.

The company reported in its Q2 post today that it has decided to scrap ZF874 after a patient demonstrated elevated liver enzymes — a classic red safety flag — in a Phase I study for alpha-1-antitrypsin (A1AT).

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Illustration: Kim Ryu for Endpoints News

Why non-opi­oid pain drugs keep fail­ing — and what's next for the field

In 1938, Rita Levi-Montalcini was forced to move her lab into her bedroom in Turin, as Mussolini’s facist government expelled Jewish people from studying or working in schools in Italy. Levi-Montalcini, then just a few years out of medical school and using sewing needles as scalpels in her makeshift lab, would soon discover nerve growth factor, or NGF, in chicken embryos.

Her discoveries formed the basis of our understanding of the peripheral nervous system and how cells talk to each other, and Levi-Montalcini went on to win the Nobel Prize in 1986. Much later, NGF was hailed as a promising target for new pain therapies, with some analysts quoting an $11 billion market. However, the latest anti-NGF candidate, Pfizer and Eli Lilly’s tanezumab, was rejected by the FDA last year because of a side effect that dissolved bone in some of its patients.

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Hervé Affagard, MaaT Pharma CEO

One year in­to clin­i­cal hold, FDA has more ques­tions about 'pooled' mi­cro­bio­me ther­a­py

The FDA is still wary about a trial testing a microbiome therapy in patients with steroid-resistant acute graft-versus-host disease (aGVHD).

A year after MaaT Pharma’s IND application in the US was first met with a clinical hold, the French biotech said the agency is maintaining the hold. The crux of the matter, MaaT suggested, has to do with the way it puts together its drug candidate, which is administered as an enema (i.e. an injection of fluid into the bowel).

Pfiz­er launch­es re­bate pro­gram for rare dis­ease pa­tients who have to stop tak­ing Panzy­ga

Pfizer is launching its second-ever rebate program, this time for Panzyga, its treatment for a rare neurological disease of the peripheral nerves.

The program began last month, according to STAT which first reported the news, and offers a refund of out-of-pocket costs for patients who must discontinue their course before the fifth treatment for “clinical reasons.”

Panzyga was approved back in 2018 to treat primary immunodeficiency (PI) in patients two years and older and chronic immune thrombocytopenia (cITP) in adults. It has since picked up an indication in chronic inflammatory demyelinating polyneuropathy (CIDP), a condition that’s characterized by weakness of the arms or legs, tingling or numbness, and a loss of deep tendon reflexes, according to the NIH.