Takeda (file photo)

Ear­ly da­ta on Takeda's dengue vac­cine is promis­ing, but wait for the full dataset

Take­da’s an­swer to Sanofi’s con­tro­ver­sial dengue vac­cine is here. The Japan­ese drug­mak­er, which is hop­ing to avert the chal­lenges faced by its French ri­val to de­vel­op a prod­uct for the mos­qui­to-borne dis­ease, broke out the num­bers from the first tranche of its piv­otal tri­al on Wednes­day.

The place­bo-con­trolled tri­al, called TIDES, is test­ing the im­pact of two dos­es of the vac­cine — TAK-003 — in pre­vent­ing dengue fever, trig­gered by any of the four vi­ral strains, in more than 19,000 pa­tients aged four to 16 years in parts of Latin Amer­i­ca and Asia where the dis­ease is en­dem­ic.

The vac­cine’s ef­fi­ca­cy, on av­er­age, hit 80.2% — meet­ing the pri­ma­ry end­point of the first part of the tri­al. The sub­jects were giv­en the two dos­es three months apart — the main goal was as­sessed 15 months af­ter the first dose (12 months af­ter the sec­ond dose).

Ef­fi­ca­cy for serotype 2 reg­is­tered at a splen­did 97.7% — but serotype 1 came in at 73.7% and serotype 3 was even worse at 62.6%. There were not enough cas­es of serotype 4 for as­sess­ment, Take­da said, adding that the per­cent­age of par­tic­i­pants with se­ri­ous ad­verse events was sim­i­lar across both the drug and place­bo arms.

“These re­sults sup­port a po­ten­tial ben­e­fit re­gard­less of pre­vi­ous dengue ex­po­sure or age, and the on­set of some pro­tec­tion af­ter the first dose sug­gests that the vac­cine may be use­ful in the con­text of out­break con­trol or trav­el vac­ci­na­tion; how­ev­er, re­port­ed vari­a­tion in serotype-spe­cif­ic ef­fi­ca­cy needs care­ful con­sid­er­a­tion,” re­searchers wrote in a re­port about the tri­al in the New Eng­land Jour­nal of Med­i­cine. 

The sec­ond por­tion of the study will track par­tic­i­pants for an­oth­er six months, while the third and fi­nal por­tion of the study will trail pa­tients for an ad­di­tion­al three years. Mean­while, Take­da is for­ti­fy­ing its man­u­fac­tur­ing ap­pa­ra­tus in ad­vance of the vac­cine’s ap­proval — it has just al­so chris­tened a €130 mil­lion plant in Ger­many.

Take­da is hop­ing its ef­fort will not crash and burn like Sanofi, which once har­bored block­buster ex­pec­ta­tions for Deng­vax­ia, the world’s first dengue vac­cine. That dream was shat­tered af­ter the French group was forced to con­cede in late 2017 that vac­cine could en­hance the risk of se­vere dengue in chil­dren who had nev­er been ex­posed to the virus — on­ly af­ter the Philip­pines used $70 mil­lion worth of the shot in a mass vac­ci­na­tion cam­paign for 800,000 chil­dren.

In May, the US health reg­u­la­tor sanc­tioned the use of Deng­vax­ia as the first-ever prod­uct to pre­vent the mos­qui­to-borne dis­ease in chil­dren who have pre­vi­ous­ly con­tract­ed dengue and who live in ar­eas rife with the dis­ease. The vac­cine — which is ad­min­is­tered as three sep­a­rate in­jec­tions — was found to be rough­ly 76% ef­fec­tive in pre­vent­ing symp­to­matic dengue dis­ease in in­di­vid­u­als 9 through 16 years of age who pre­vi­ous­ly had lab­o­ra­to­ry-con­firmed dengue dis­ease, the FDA not­ed. But in the Unit­ed States and its ter­ri­to­ries, no avail­able tests have been cleared by the FDA to de­ter­mine a pre­vi­ous dengue in­fec­tion, Sanofi has ac­knowl­edged.

Even be­fore the Philip­pines’ pub­lic health cri­sis, ex­perts had warned that vac­ci­na­tion with Deng­vax­ia in those who had not al­ready been in­fect­ed by one of the four dif­fer­ent serotypes of the virus faced a po­ten­tial­ly life-threat­en­ing fever up­on sub­se­quent in­fec­tion. This is be­cause their bod­ies would like­ly treat the first re­al dengue in­fec­tion as their sec­ond, thanks to the vac­cine. Ac­cord­ing to the FDA, rough­ly 95% of all se­vere/hos­pi­tal­ized cas­es of dengue are as­so­ci­at­ed with sec­ond dengue virus in­fec­tion.

The dengue virus is wide­spread across the trop­ics. Se­vere dengue was first rec­og­nized in the 1950s dur­ing dengue epi­demics in the Philip­pines and Thai­land, cur­rent­ly af­fect­ing most Asian and Latin Amer­i­can coun­tries, and is con­sid­ered a lead­ing cause of hos­pi­tal­iza­tion and death among chil­dren and adults in these re­gions, ac­cord­ing to the WHO. The CDC es­ti­mates that each year, about 400 mil­lion dengue virus in­fec­tions oc­cur glob­al­ly. The dengue virus is car­ried by fe­male Aedes ae­gyp­ti mos­qui­toes (and to a less­er ex­tent, Ae. al­bopic­tus) — the same species that al­so trans­mits chikun­gun­ya, yel­low fever and Zi­ka.

2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
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FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

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Every few years, a public health crisis (think Ebola, Zika) spurred by a rogue pathogen triggers a small-biotech rally, as drugmakers emerge from the woodwork with ambitious plans to treat the mounting outbreak. In most cases, that enthusiasm never quite delivers.

Things are no different, as the coronavirus outbreak in Wuhan, China takes hold. There have been close to 300 confirmed human infections in China, and at least four deaths. Coronaviruses are a large family of viruses, which include MERS and SARS. On Tuesday, the CDC reported the virus was detected in a US traveler returning from Wuhan.

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Who are the young bio­phar­ma lead­ers shap­ing the in­dus­try? Nom­i­nate them for End­points' spe­cial re­port

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BeiGene lines up its first shot at crack­ing the megablock­buster PD-1 mar­ket for lung can­cer. But can they over­come un­der­dog sta­tus?

BeiGene took another big step towards challenging Merck, Bristol-Myers Squibb, AstraZeneca and some other Big Pharma heavyweights for a share of the lucrative lung cancer market for the PD-(L)1s racking up billions in annual revenue.

The China-based biotech $BGNE run by CEO John Oyler posted positive top-line progression-free survival results for their pivotal Chinese study on their PD-1 antibody tislelizumab combined with chemo for squamous non-small cell lung cancer in frontline cases. Squamous NSCLC accounts for about 30% of the overall lung cancer market.

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Brex­it fears, Wood­ford woes over­shad­owed UK biotech and cut 2019 fi­nanc­ing by al­most half

The venture tide might have subsided, the IPO window may be closing and certain listed biotechs may be having a tough time amid Neil Woodford’s well-publicized demised, but there’s still plenty to celebrate in the UK BioIndustry Association’s eyes.

Overall investment in UK biotech last year fell from the record-breaking £2.2 billion levels of 2018 to £1.3 billion — including £679 million in venture capital, a meager £64 million in IPOs plus £596 million when you add up all public financings, according to a new report from the BIA.

Blue­print Med­i­cines po­ten­tial­ly de­lays Ay­vak­it de­ci­sion; Con­trol beats treat­ment in mesothe­lioma tri­al

→ Blueprint Medicines filed an amendment to its application to get the gastrointestinal stromal tumor (GIST) drug Ayvakit approved in fourth-line GIST, the company disclosed in the prospectus for a new $325 million public offering.  Blueprint got a big accelerated OK on the drug this month in a particular mutation, but because the FDA decided to split their review in two, they didn’t hear on fourth-line GIST. They were supposed to hear before February 14, but this amendment could push that date back by 3 months. Blueprint wrote that the amendment is designed to allow the company to comply with the FDA’s request for data from the Phase III VOYAGER before they give a judgment.