Jean-Jacques Bienaimé (BioMarin via Youtube)

FDA opens up an eth­i­cal can of worms with ac­cel­er­at­ed ap­proval for first drug for un­der­ly­ing ge­net­ic cause of dwarfism

The FDA on Fri­day signed off on an ac­cel­er­at­ed ap­proval for Bio­Marin’s Vox­zo­go (vosori­tide) in­jec­tion, the first treat­ment to tar­get the un­der­ly­ing ge­net­ics of dwarfism, which can in­crease the height of chil­dren five years of age and old­er with the con­di­tion.

There­sa Ke­hoe

The in­jec­tion, which Bio­marin said will have an an­nu­al net price of $240,000, works by bind­ing to a spe­cif­ic re­cep­tor called the na­tri­uret­ic pep­tide re­cep­tor-B, which re­duces the growth reg­u­la­tion gene’s ac­tiv­i­ty and stim­u­lates bone growth in chil­dren.

“To­day’s ap­proval ful­fills an un­met med­ical need for more than 10,000 chil­dren in the Unit­ed States,” said There­sa Ke­hoe, di­rec­tor of FDA’s Di­vi­sion of Gen­er­al En­docrinol­o­gy.

The ap­proval is based on a Phase III place­bo-con­trolled tri­al in which 121 par­tic­i­pants were ran­dom­ly as­signed to re­ceive ei­ther Vox­zo­go in­jec­tions or a place­bo.

“Re­searchers mea­sured the par­tic­i­pants’ an­nu­al­ized growth ve­loc­i­ty, or rate of height growth, at the end of the year. Par­tic­i­pants who re­ceived Vox­zo­go grew an av­er­age 1.57 cen­time­ters taller com­pared to those who re­ceived a place­bo,” the FDA said.

A con­di­tion of the ac­cel­er­at­ed ap­proval is that Bio­Marin must run a post-mar­ket­ing study that will as­sess the fi­nal adult height.

Jean-Jacques Bi­en­aimé, chair­man and CEO of Bio­Marin, said in a state­ment, “Vox­zo­go is a med­ical first that is root­ed in Bio­Marin’s fo­cus on mol­e­c­u­lar ge­net­ics and tar­gets the un­der­ly­ing cause of the con­di­tion. More than a decade of sci­en­tif­ic re­search un­der­pins the med­ical ad­vance that Vox­zo­go rep­re­sents. We thank the FDA for rec­og­niz­ing its val­ue as the first ther­a­peu­tic treat­ment op­tion for chil­dren with achon­dropla­sia.”

But there’s an eth­i­cal ques­tion at the heart of the ap­proval too. Ac­cord­ing to STAT News, or­ga­ni­za­tions such as Lit­tle Peo­ple of Amer­i­ca have long sought to ad­vo­cate for fair­ness while not­ing that achon­dropla­sia, the most com­mon form of dwarfism, doesn’t pre­clude them from a ful­fill­ing life, and drugs like Vox­zo­go could be a threat to the com­mu­ni­ty they’ve built.

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

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

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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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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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Janet Woodcock (AP Images)

Janet Wood­cock plots her fu­ture at FDA, with se­nior ad­vi­sor role to fall back on if Califf wins con­fir­ma­tion

Acting FDA commissioner Janet Woodcock has been the face of just about every drug approval decision at the agency since the turn of the century. Since the pandemic began, she’s moved between the top of the drugs center to the head of therapeutics at Operation Warp Speed, leading the drive for work on Covid-targeted mAbs and antivirals.

Looking forward — and pending a quick Senate confirmation to cement Rob Califf’s return to the top of FDA early next year — Woodcock’s role at the agency will again be in flux.

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Richard Pazdur (via AACR)

Ac­cel­er­at­ed ap­proval re­forms need mean­ing­ful con­fir­ma­to­ry tri­al im­prove­ments, pro­fes­sors write in Sci­ence

Outside of Covid-19, 2021 has been the year of the accelerated approval.

Beginning last spring, FDA openly challenged six “dangling” accelerated approvals (hadn’t confirmed their clinical benefit yet), three of which were later pulled by the companies.

Then in June, FDA pulled out the accelerated approval pathway, seemingly out of nowhere, to sign off on Biogen’s controversial Alzheimer’s drug Aduhelm. It hadn’t even been mentioned at the drug’s adcomm.

In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

Lan Huang, BeyondSpring CEO

Months af­ter shock­ing in­vestors with lung can­cer win, Be­yond­Spring's lead drug hits road­block at the FDA

BeyondSpring shocked investors in early August after its once-marginal lead drug suddenly showed a lot of promise in a common form of lung cancer. With hopes high, the FDA has now slammed the door on that drug in another indication — does that spell bad news for BeyondSpring’s Cinderella story?

The FDA issued BeyondSpring a complete response letter for its plinabulin in combination with granulocyte colony-stimulating factor (G-CSF) for the prevention of chemotherapy-induced neutropenia, effectively shutting down the drug’s immediate chances at a marketing approval, the biotech said Wednesday.

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