Christophe Weber, Takeda CEO (Miho Takahashi/The Yomiuri Shimbun via AP Images)

FDA of­fers sup­port for Takeda's po­ten­tial cy­tomegalovirus drug ahead of ad­comm

Af­ter al­most two decades of dis­cus­sions with FDA re­gard­ing the de­vel­op­ment of Take­da’s po­ten­tial drug for post-trans­plant cy­tomegalovirus (CMV), which it bought in its ac­qui­si­tion of Shire in 2019, the agency seems to be of­fer­ing pos­i­tive marks for the drug’s safe­ty and ef­fi­ca­cy pro­file ahead of Thurs­day’s ad­comm.

Ac­cord­ing to FDA’s brief­ing doc­u­ments re­leased ahead of the meet­ing, marib­avir proved safe across mul­ti­ple stud­ies and sta­tis­ti­cal­ly su­pe­ri­or to in­ves­ti­ga­tor-as­signed treat­ment (IAT) in a Phase III tri­al, which Take­da an­nounced ear­li­er this year.

FDA’s con­cerns about dis­con­tin­u­a­tions in the IAT arm of the tri­al al­so did not over­shad­ow that sta­tis­ti­cal suc­cess.

While FDA not­ed the Phase III re­sults “ap­peared to be dri­ven by treat­ment dis­con­tin­u­a­tion in the IAT group (dis­con­tin­u­a­tion was con­sid­ered treat­ment fail­ure in the pri­ma­ry analy­sis),” sev­er­al sen­si­tiv­i­ty analy­ses of the pri­ma­ry end­point “showed that marib­avir re­mained sta­tis­ti­cal­ly su­pe­ri­or to IAT for the pri­ma­ry end­point, and thus the treat­ment ef­fect re­mains ro­bust.”

In ad­di­tion­al im­por­tant sub­group analy­ses, FDA said marib­avir re­mained su­pe­ri­or to IAT for the pri­ma­ry end­point with the ex­cep­tion of the “re­frac­to­ry” sub­group and for the sub­group of pa­tients with CMV dis­ease.

But FDA not­ed that one of its “ma­jor con­cerns” in the tri­al “was the po­ten­tial for bias due to the open-la­bel de­sign of the tri­al. Al­though bias is sug­gest­ed by the demon­stra­tion of more dis­con­tin­u­a­tions in the IAT arm than in the marib­avir arm, bias can­not be de­fin­i­tive­ly demon­strat­ed or ruled out, par­tic­u­lar­ly be­cause of the known safe­ty pro­file of the drugs in the IAT arm.”

And over­all, the agency said marib­avir “pro­vides some ad­van­tages over cur­rent­ly avail­able ther­a­pies, i.e., it ap­pears to have a bet­ter safe­ty pro­file, with taste dis­tur­bance be­ing the most com­mon ad­verse re­ac­tion as­so­ci­at­ed with its use. In these tri­als, most sub­jects did not dis­con­tin­ue marib­avir due to taste dis­tur­bance or oth­er ad­verse re­ac­tions. Ad­di­tion­al­ly, marib­avir is avail­able as an oral tablet (as is val­gan­ci­clovir), pro­vid­ing ease of ad­min­is­tra­tion.”

Ad­comm mem­bers will vote on two ques­tions on whether the over­all ben­e­fit-risk as­sess­ment is fa­vor­able for marib­avir to treat trans­plant re­cip­i­ents with CMV in­fec­tion and dis­ease, with one ques­tion ask­ing if that risk-ben­e­fit pro­file is still fa­vor­able with or with­out those with geno­typ­ic re­sis­tance to oth­er an­tivi­rals, in­clud­ing gan­ci­clovir, val­gan­ci­clovir, fos­car­net or cid­o­fovir.

If ap­proved, Take­da’s marib­avir could be the first drug specif­i­cal­ly ap­proved for treat­ment of post-trans­plant CMV in­fec­tion, which FDA says is one of the most com­mon in­fec­tious com­pli­ca­tions in post-trans­plant re­cip­i­ents. FDA al­so not­ed that the avail­able CMV an­tivi­ral drugs, in­clud­ing gan­ci­clovir, val­gan­ci­clovir, fos­car­net and cid­o­fovir, all have sig­nif­i­cant tox­i­c­i­ties.

An ap­proval would al­so cap a long and rocky his­to­ry for the drug, which has changed hands sev­er­al times over the last two decades through pos­i­tive and neg­a­tive tri­als.

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 then 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, in­creas­ing the dose in var­i­ous phar­ma­co­ki­net­ic and ef­fi­ca­cy stud­ies, and in 2016, a Phase II study showed that it helped clear in­fec­tions. The FDA com­mend­ed the re­sults with a break­through des­ig­na­tion in 2018. And the fol­low­ing year, Take­da com­plet­ed its ac­qui­si­tion of Shire for $62 bil­lion.

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.

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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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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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).

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.

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.

Horizon's back-to-school campaign for children with cystinosis includes an all about me poster as part of a care package box.

Hori­zon read­ies kids and fam­i­lies for back to school with week­long ac­tiv­i­ties around rare dis­ease cysti­nosis

Going back to school is usually a bumpy readjustment from summer freedom for all kids, but especially for kids with chronic health conditions. Horizon Therapeutics is hoping to help smooth the way for some who have the rare disease cystinosis. Cystinosis is a genetic disease that causes the amino acid cystine to build up in different tissues and organs.

The “Gear Up” for school campaign is running all week with different online and at-home events and activities for families and children with cystinosis. Each family who signed up receives a care package mailed to their home including an activity coloring book “Michael’s Show-and-Tell.” The book tells Michael’s story about living with cystinosis while offering kids matching, coloring and finding object games along with information.

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Phar­mas spend mil­lions on di­a­betes ad­ver­tis­ing, but few pa­tients can re­call brand names — sur­vey

While many Big Pharma diabetes brands spend millions of dollars on TV ads every year, most people with type 2 diabetes don’t recognize specific drug brand names, according to a new study.

No brand garnered more than 30% recognition in Phreesia Life Science’s latest in-office patient survey of more than 4,000 adults with type 2 diabetes. Eli Lilly’s Trulicity topped the list as the most recognized brand with 29% of those surveyed recalling it, followed by Boehringer Ingelheim and Lilly’s Jardiance at 27% and Merck’s Januvia and Novo Nordisk tying for the third spot with 24%. Meanwhile, 76% of the patients surveyed were familiar with the generic treatment metformin.

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Faced with thou­sands of opi­oid law­suits, En­do says it will like­ly file for bank­rupt­cy 'im­mi­nent­ly'

Endo International will likely be the next pharma company to file for bankruptcy under a mountain of opioid lawsuits.

The Dublin, Ireland-based company revealed in its Q2 results on Tuesday that it’s in talks with first lien creditors, and that “these negotiations will likely result in a pre-arranged filing under Chapter 11 of the U.S. Bankruptcy Code by Endo International plc and substantially all of its subsidiaries, which could occur imminently.”