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.

Com­mu­ni­cat­ing the val­ue of pre­ci­sion med­i­cine

By Natasha Cowan, Content Marketing Manager at Blue Latitude Health.
Many stakeholders are confused by novel precision medicines, including patients and healthcare professionals. So, how can industry help them to navigate this complexity?

Precision medicine represents a new paradigm in healthcare. It embodies the shift from treating many patients with the same therapy, to having the tools to identify the best treatment for every patient.

Spe­cial re­port: Twen­ty ex­tra­or­di­nary women in bio­phar­ma R&D who worked their way to the top

What differentiates a woman leader in biopharma R&D from a man?

Not much, except there are fewer of them in senior posts. Data suggest women are not more risk-averse, family-oriented or less confident than their male counterparts — indeed the differences between the two sexes are negligible. But a glance at the top R&D positions in Big Pharma leaves little doubt that upward migration in the executive ranks of biopharma R&D is tough.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 64,900+ biopharma pros reading Endpoints daily — and it's free.

The lat­est Cin­derel­la sto­ry in on­col­o­gy ends with a sud­den rout as up­dat­ed da­ta dis­play spooks in­vestors

NextCure’s turn as the Cinderella of cancer-focused biotechs was short-lived.
Just a few days after its shares $NXTC zoomed up more than 250% on some very early stage results in a SITC abstract, a more complete analysis over the weekend spiked the hype and left investors in high dudgeon as the stock price collapsed back towards earth Monday.
The focus at NextCure is centered on NC318, an antibody that is intended to shut down the immunosuppressive Siglec-15 — or S-15 — target. After adding a small group of patients to the readout, investigators circled 2 clinical responses, a complete and partial response, along with 4 stable disease cases in non-small cell lung cancer.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 64,900+ biopharma pros reading Endpoints daily — and it's free.

Te­va spin­out rais­es $85M in IPO; No­var­tis beefs up gener­ics unit with $440M deal

→ After Teva spinout 89bio recently announced that its IPO was being held up, the company is back in the game offering 5,304,687 shares at a price of $16 per share. The company has raised $84.9 million IPO in gross proceeds and will be listed under the ticker symbol $ETNB. BofA Securities, SVB Leerink and RBC Capital Markets are the joint book-running managers for the offering. Oppenheimer & Co is the co-manager for the offering.
→ Looking to amp up its presence in Japan’s hospitals, Novartis has struck a deal to buy out Aspen’s portfolio of generics in the world’s third largest healthcare market. The pharma giant is paying $440 million for Aspen’s Japanese subsidiary.
→ Novartis said tropifexor, a non-bile acid FXR agonist, has scored on several key biomarkers of NASH in a Phase IIb trial, including reductions in hepatic fat, alanine aminotransferase and body weight compared to a placebo at 12 weeks.

Break­through sta­tus and promise of a speedy re­view ar­rives for Op­di­vo/Yer­voy com­bi­na­tion as Bris­tol-My­ers bites at Bay­er

Its frontline and single-agent aspirations have been set back, but Bristol-Myers Squibb just took a big step forward in its efforts to apply its checkpoint inhibitor Opdivo to liver cancer. The FDA has granted breakthrough status and priority review to a combination, second-line treatment.

The designation is for Opdivo (nivolumab) in combination with Yervoy (ipilimumab),  for treating advanced hepatocellular carcinoma (HCC), the most common form of liver cancer. The PD-L1 drug was already approved as a single-agent, second-line treatment for HCC. A PDUFA date was set for March 10, 2020 — just 4 months from now.

Third time un­lucky: Lipocine's lat­est quest to mar­ket their oral testos­terone drug snubbed again by FDA

Lipocine’s latest attempt at securing approval for its oral testosterone drug has fizzled yet again.

The Utah-based drug developer on Monday said the FDA has spurned its marketing application, indicating that some efficacy data on the drug, Tlando, was not up to scratch to treat male hypogonadism, a condition characterized by low production of the hormone testosterone, which is responsible for maintaining muscle bulk, bone growth, and sexual function.

UP­DAT­ED: De­cry­ing 'ar­bi­trary and capri­cious' ac­tion, Re­genxBio sues FDA over clin­i­cal holds on gene ther­a­py

When RegenxBio disclosed that the FDA had placed a partial clinical hold on one of its lead gene therapies, execs outlined several customary next steps: continuing assessment and monitoring, delaying a related IND filing, and working with the FDA to address the matter.

As it turned out, they were planning something much less mundane. Two days after announcing the hold in its Q3 update, RegenxBio filed a lawsuit seeking to set it aside, the FDA Law Blog noted.

Roche's SMA chal­lenge to Bio­gen's Spin­raza fran­chise looms larg­er with piv­otal win

Roche has just landed a crucial advance in scoring a come-from-behind win on the spinal muscular atrophy field, giving Novartis and Biogen a run for their money.

The update was brief, but Roche said risdiplam hit the primary endpoint in the placebo-controlled pivotal SUNFISH trial, meeting the threshold for change from baseline in the Motor Function Measure 32 (MFM-32) scale after one year of treatment. The results, which is the second, confirmatory portion of a two-part study, involved 180 patients with type 2 or 3 spinal muscular atrophy between 2 and 25 years old.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 64,900+ biopharma pros reading Endpoints daily — and it's free.

Roche steers Gazy­va in­to a new PhI­II pro­gram af­ter com­bo shows promise in lu­pus nephri­tis study

Roche is working on putting together a late-stage study for its monoclonal antibody Gazyva in patients with severe kidney disease associated with lupus after a combination approach helped patients in a mid-stage study.

The 125-patient NOBILITY trial evaluated Gazyva, combined with standard-of-care treatment mycophenolate mofetil or mycophenolic acid and corticosteroids, versus standard treatment alone. The combo met the main goal of inducing a statistically superior complete renal response (CRR) of 40% at week 76, versus 18% in patients given standard treatment, Roche said.