FDA staff large­ly un­fazed by CV sig­nal in Am­gen os­teo­poro­sis drug tri­als

FDA staff braved the snow and the fed­er­al shut­down to post their re­view of Am­gen’s once-re­ject­ed os­teo­poro­sis drug on Mon­day, un­der­scor­ing that the ef­fi­ca­cy of the drug in post­menopausal women had been es­tab­lished, and sug­gest­ing that the CV sig­nal ob­served in two tri­als may not be a sig­nif­i­cant wor­ry.

The re­view comes days af­ter Am­gen and part­ner UCB se­cured Japan­ese ap­proval for the drug, ro­mosozum­ab, and pre­cedes a meet­ing of in­de­pen­dent ex­perts on Wednes­day who will make their rec­om­men­da­tion on the ap­prov­abil­i­ty of the drug in the Unit­ed States. Ro­mosozum­ab — which is to be sold un­der the brand name Eveni­ty — func­tions pre­dom­i­nant­ly as a bone an­a­bol­ic agent that stim­u­lates bone growth.

The mon­o­clon­al an­ti­body was test­ed in three late-stage stud­ies: the 7,180-pa­tient FRAME study in post­menopausal women with os­teo­poro­sis, which test­ed the drug against a place­bo; the 4,093-pa­tient ARCH study in post­menopausal women in os­teo­poro­sis, which test­ed the drug against an os­teo­poro­sis drug orig­i­nal­ly made by Mer­ck called al­en­dronate; and the 245-pa­tient BRIDGE study in men with os­teo­poro­sis, which test­ed the drug against a place­bo.

All three piv­otal stud­ies showed the drug was ef­fec­tive, but the ARCH and BRIDGE tri­al demon­strat­ed a sig­nal of car­dio­vas­cu­lar-re­lat­ed se­ri­ous ad­verse events, which led to the FDA is­su­ing a com­plete re­sponse let­ter to the com­pa­nies, af­ter they had ap­plied for ap­proval in post­menopausal women with os­teo­poro­sis. Tak­ing in­to ac­count the CV sig­nal and feed­back from the FDA about the pauci­ty of an­a­bol­ic agents, the duo re-sub­mit­ted an ap­pli­ca­tion to mar­ket drug last year, but for a nar­row­er pa­tient pop­u­la­tion: post­menopausal women with os­teo­poro­sis who car­ry a high risk of frac­ture. They al­so pro­posed a boxed warn­ing as well as a pre­cau­tion for car­dio­vas­cu­lar risk on the drug’s la­bel, if ap­proved. Mean­while, the drug is un­der re­view in Eu­rope.

Glob­al­ly, 1 in 3 women over age 50 will ex­pe­ri­ence os­teo­porot­ic frac­tures, ac­cord­ing to the In­ter­na­tion­al Os­teo­poro­sis Foun­da­tion.

In its re­view, FDA staff agreed that the ef­fec­tive­ness of ro­mosozum­ab for the treat­ment of post­menopausal os­teo­poro­sis had been es­tab­lished, but ques­tioned whether the CV sig­nal seen in ARCH and BRIDGE were gen­er­al­iz­able to the US pop­u­la­tion, giv­en that en­rolled pa­tients from the US on­ly ac­count­ed for 1.8% of the ARCH study, and 1.4% of the BRIDGE study. In their sug­gest­ed ques­tions for in­de­pen­dent pan­el, the agency’s re­view­ers did not stress the CV is­sue.

“The docs read most­ly be­nign and dis­cus­sion/vot­ing ques­tions are not as crit­i­cal on CV risk, sup­port­ing a fa­vor­able pan­el vote on Wed (1/16) and an even­tu­al ap­proval lat­er in H1:19,” Jef­feries an­a­lysts wrote in a note, adding that Lil­ly’s os­teo­poro­sis drug For­teo car­ries a black box warn­ing high­light­ing the risk of can­cer and still rakes in about $2 bil­lion.

The drug “rep­re­sents a mod­est $500 mil­lion world­wide up­side op­por­tu­ni­ty not wide­ly ac­count­ed by con­sen­sus, and the drug has shown strong ef­fi­ca­cy (beat­ing Fos­amax by 48-50%) along with an ac­cept­able safe­ty pro­file. The pri­or safe­ty sig­nal seen in the small­er of two key Phase III stud­ies (ARCH vs FRAME) seems more spu­ri­ous than con­cern­ing to us,” they not­ed.

Grow­ing ac­cep­tance of ac­cel­er­at­ed path­ways for nov­el treat­ments: but does reg­u­la­to­ry ap­proval lead to com­mer­cial suc­cess?

By Mwango Kashoki, MD, MPH, Vice President-Technical, and Richard Macaulay, Senior Director, of Parexel Regulatory & Access

In recent years, we’ve seen a significant uptake in the use of regulatory options by companies looking to accelerate the journey of life-saving drugs to market. In 2018, 73% of the novel drugs approved by the U.S. Federal Drug Administration (FDA) were designated under one or more expedited development program categories (Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval).ᶦ

Sanofi out­lines big API plans as coro­n­avirus out­break re­port­ed­ly threat­ens short­age of 150 drugs

As the world becomes increasingly dependant on Asia for the ingredients of its medicines, Sanofi sees business to be done in Europe.

The French drugmaker said it’s creating the world’s second largest active pharmaceutical ingredients (API) manufacturer by spinning out its six current sites into a standalone company: Brindisi (Italy), Frankfurt Chemistry (Germany), Haverhill (UK), St Aubin les Elbeuf (France), Újpest (Hungary) and Vertolaye (France). They have mapped out €1 billion in expected sales by 2022 and 3,100 employees for the new operations headquartered in France.

UP­DAT­ED: NGM Bio takes leap for­ward in crowd­ed NASH field

South San Francisco-based NGM Bio may have underwhelmed with its interim analysis of a key cohort from a mid-stage NASH study last fall — but stellar topline data unveiled on Monday showed the compound induced significant signs of antifibrotic activity, NASH resolution and liver fat reduction, sending the company’s stock soaring.

There are an estimated 50+ companies focused on developing drugs for non-alcoholic steatohepatitis, or NASH, a common liver disease that has long flummoxed researchers. The first wave of NASH drug developers struggled with efficacy as well as safety — and companies big and small have crashed and burned.

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Mickey Kertesz, KidsandArtOrg via YouTube

Soft­Bank's newest, $165M biotech in­vest­ment looks for in­fec­tious traces in the blood

SoftBank has found its newest biotech investment.

The Japanese bank has invested $165 million into Karius, a company that uses blood tests to diagnose infectious diseases, as part of its new Vision Fund 2. The full scope of the new fund has yet to be announced, but the first and newly-beleaguered Vision Fund poured $100 billion into technology companies, including the biotechs Vir Biotechnology and Roivant and the sequencing company 10x Genomics.

Methicillin-resistant Staph aureus (Shutterstock)

FDA grants ‘break­through’ sta­tus to an­tibi­ot­ic al­ter­na­tive as Con­tra­Fect rush­es to join fight against su­per­bug

An experimental drug that promises to be the first anti-infective agent to prove superior to vancomycin — an antibiotic approved in 1958 — has notched the FDA’s “breakthrough” status.

ContraFect said the designation was based on Phase II data in which exebacase was tested against a superbug known as methicillin-resistant Staph aureus, or MRSA. In a subgroup analysis, the clinical responder rate at day 14 was 42.8% higher than that among those treated with standard of care, the company said (p=0.010).

Zhong Nanshan, CGTN via YouTube

Har­vard joins coro­n­avirus fight with $115 mil­lion and a high-pro­file Chi­nese part­ner

For two months, as the novel coronavirus swelled from a few early cases tied to a Wuhan market to a global epidemic, most of the world’s focus and dollars have flowed toward emergency initiatives: building vaccines at a record pace, plucking experimental antivirals out of freezers to see what sticks and immunizing mice for new antibodies.

Now a new and well-funded collaboration between Harvard and a top Chinese research institute will play the long game. In a 5-year, $115 million initiative backed by China Evergrande Group, researchers from the Harvard Medical School, Harvard T.H. Chan School of Public Health and Guangzhou Institute for Respiratory Health will study the virus in an effort to develop therapies against infections by the novel coronavirus, known as SARS–CoV-2, and to prevent new ones.

No­var­tis gets a boost in block­buster mul­ti­ple scle­ro­sis race with Roche

In the first step of what’s likely to be a long and uphill battle for the drugmaker, the FDA has accepted Novartis’s BLA submission for a new multiple sclerosis drug and given it priority review. The PDUFA date for the potential blockbuster drug is in June.

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Juergen Horn

An­i­mal health vet Juer­gen Horn makes new an­ti­body play for pets, rak­ing $15M in Se­ries A haul

Zoetis forked over $85 million in 2017 to acquire Nexvet Biopharma and its pipeline of monoclonal antibodies. Juergen Horn, Nexvet’s former chief product development officer, has now secured $15 million for his own biologic company for animals: Invetx.

Buoyed by emerging advances in gene therapies for humans, scientists have started looking at harnessing the technology for animals setting up companies such as Penn-partnered Scout Bio and George Church-founded Rejuvenate Bio. But akin to Nexvet, Invetx is working on leveraging the time-tested science of monoclonal antibodies to treat chronic diseases that afflict man’s best friend.

As coro­n­avirus out­break reach­es 'tip­ping point,' GSK lends ad­ju­vant tech to Chi­nese part­ner armed with pre­clin­i­cal vac­cine

As the coronavirus originating out of Wuhan spreads to South Korea, Italy and Iran, stoking already intense fears of a pandemic, GlaxoSmithKline has found another pair of trusted hands to place its adjuvant system. China’s Clover Biopharmaceuticals will add the adjuvant to its preclinical, protein-based vaccine candidate against SARS-CoV-2.

Clover, which is based in the inland city of Chengdu, boasts of a platform dubbed Trimer-Tag that produces covalently-trimerized fusion proteins. Its candidate, COVID-19 S-Trimer, resembles the viral spike (S)-protein found in the virus.