With its dengue vac­cine in the reg­u­la­to­ry queue, Take­da out­lines longterm fol­lowup da­ta that it says keep it out of Deng­vax­i­a's shad­ow

When Sanofi pub­lished longterm fol­lowup re­sults from a trio of Phase III tri­als for its dengue vac­cine in 2015, in­ves­ti­ga­tors flagged a con­cern­ing ob­ser­va­tion that they weren’t able to ex­plain: In the third year post-vac­ci­na­tion, chil­dren younger than 9 who got the jabs were more like­ly to end up in the hos­pi­tal than those in the con­trol group.

The hos­pi­tal­iza­tion im­bal­ance didn’t stop Sanofi from clinch­ing the ap­proval to start the world’s first large-scale vac­ci­na­tion cam­paign in the Philip­pines with its vac­cine, Deng­vax­ia. But even though pub­lic health of­fi­cials tried to skirt it by lim­it­ing the in­oc­u­la­tion dri­ve to old­er chil­dren and adults, the is­sue — which Sanofi was lat­er ac­cused of play­ing down — would come back to haunt the ef­fort. Kids and adults were de­vel­oped with se­vere fever af­ter vac­cines, in some cas­es lethal, spark­ing na­tion­wide pan­ic and forc­ing the Phillip­pine gov­ern­ment to shut down the pro­gram. Even though Deng­vax­ia even­tu­al­ly got adopt­ed in oth­er coun­tries, the fi­as­co left its scars.

Take­da, which has been push­ing its own dengue vac­cine un­der that cloud for the past eight years, now has the three-year fol­lowup da­ta to sug­gest it can steer clear of that wreck­age — al­though some gaps re­main be­fore we get a com­plete pro­file of the shot.

With those re­sults now in, the Japan­ese phar­ma has al­so com­plet­ed the pack­age it needs to file with reg­u­la­tors. Take­da sub­mit­ted for a mar­ket­ing ap­proval with the EMA in March, and it’s plot­ting more in dengue-en­dem­ic coun­tries like Ar­genti­na, Brazil, Colom­bia, In­done­sia, Malaysia, Mex­i­co, Sin­ga­pore, Sri Lan­ka and Thai­land. An FDA fil­ing is ex­pect­ed to fol­low lat­er this year.

Derek Wal­lace

Hav­ing fol­lowed 20,000 study par­tic­i­pants for 36 months af­ter their sec­ond dose of TAK-003, in­ves­ti­ga­tors re­port­ed that vac­cine ef­fi­ca­cy against hos­pi­tal­ized dengue is 83.6%.

“That’s re­al­ly the com­po­nent of the ill­ness that has the most im­pact, at an in­di­vid­ual lev­el whether that’s on health or fi­nances, it’s al­so the as­pect of dengue that has the great­est im­pact on pub­lic health sys­tems and our com­mu­ni­ties,” Derek Wal­lace, the dengue pro­gram leader at Take­da, told End­points News in a pre­view.

The ef­fi­ca­cy num­bers are sim­i­lar re­gard­less of whether the vac­cine re­cip­i­ent has had a pre­vi­ous dengue in­fec­tion — 86% for the seropos­i­tive group and 77.1% for the seroneg­a­tive group — which is no­table be­cause a phe­nom­e­non known as an­ti­body-de­pen­dent en­hance­ment in virus-naïve pa­tients had been blamed for Deng­vax­ia’s prob­lems.

Over­all vac­cine ef­fi­ca­cy, as mea­sured by vi­ro­log­i­cal­ly-con­firmed dengue, reg­is­tered at 62.0%, with 65% in seropos­i­tive in­di­vid­u­als and 54.3% in seroneg­a­tive in­di­vid­u­als.

The pro­tec­tion that the vac­cine of­fers has waned across the board com­pared to the last cut of da­ta at 18 months, when Take­da tout­ed an over­all ef­fi­ca­cy rate of 73% and re­duc­tion of 90% in dengue-re­quired hos­pi­tal­iza­tion com­pared to place­bo. But the wan­ing fo­cused on what Wal­lace calls “am­bu­la­to­ry dengue” and the drop was small­er in the group that mat­tered.

But Take­da didn’t pro­vide an up­date on the break­down of ef­fi­ca­cy in each of four dengue serotypes, say­ing it will save those num­bers for pub­li­ca­tion in a peer-re­viewed jour­nal lat­er this year. At 18 months, while the ef­fi­ca­cy for dengue 1 and dengue 2 looked promis­ing, there were con­cerns about a lack of ef­fi­ca­cy for dengue 3. (For dengue 4, the da­ta were in­con­clu­sive.)

Sanofi scored ap­proval for Deng­vax­ia with Phase III da­ta that were pre­sent­ed in a slight­ly dif­fer­ent way, sug­gest­ing pooled rates of ef­fi­ca­cy for symp­to­matic dengue dur­ing the first 25 months of 60.3% — and pooled rel­a­tive risks of hos­pi­tal­iza­tion for dengue of 0.84.

Per the pro­to­col, Take­da will mon­i­tor the par­tic­i­pants for an­oth­er year and a half. Af­ter 4.5 years, it plans to test whether a boost­er would of­fer more pro­tec­tion in the long run.

“The world we live in now with Covid-19 has re­al­ly shown the po­ten­tial­ly dev­as­tat­ing im­pact that in­fec­tious dis­eases can have, and the val­ue of care­ful vac­cine de­vel­op­ments and im­ple­men­ta­tion of vac­cine pro­grams,” Wal­lace said. “In the back­ground of all that, we have dengue. Dengue has been around for decades be­fore Covid-19 and it will be around for decades to come. It’s a dis­ease that is mas­sive in its im­pact, af­fect­ing half of the world’s pop­u­la­tion and it’s not a dis­ease that we’ve got a very good han­dle on in terms of man­age­ment or pre­ven­tion.”

They’ve come a long way to ar­rive at a stage where they are prepar­ing to talk to reg­u­la­tors. Orig­i­nal­ly de­rived in the lab­o­ra­to­ries of Su­tee Yok­san at Mahi­dol Uni­ver­si­ty in Thai­land, the live-at­ten­u­at­ed vac­cine con­struct was mus­cled up at the US CDC and went through clin­i­cal stud­ies at In­vi­ra­gen be­fore Take­da snapped the biotech up in 2013, while the dengue pro­gram was still in Phase II, ac­cord­ing to a spokesper­son.

Covid-19, of course, still fig­ures promi­nent­ly in the minds of any vac­cine de­vel­op­er. Even as Take­da ham­mers out the arrange­ment for its Ger­man con­tract man­u­fac­tur­er IDT to make the ini­tial dos­es of TAK-003 should it be ap­proved (be­fore even­tu­al­ly set­ting up its own pro­duc­tion in Ger­many), it will be pro­vid­ing some man­u­fac­tur­ing slots there to make J&J’s coro­n­avirus vac­cine while help­ing Mod­er­na dis­trib­ute its shots in Japan.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.

Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.

As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

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Ex­elix­is pulls a sur­prise win in thy­roid can­cer just days ahead of fi­nal Cabome­tyx read­out

Exelixis added a thyroid cancer indication to its super-seller Cabometyx’s label on Friday — months before the FDA was expected to make a decision, and days before the company was set to unveil the final data at #ESMO21.

At a median follow-up of 10.1 months, differentiated thyroid cancer patients treated with Cabometyx (cabozantinib) lived a median of 11 months without their disease worsening, compared to just 1.9 months for patients given a placebo, Exelixis said on Monday.

Dave Lennon, former president of Novartis Gene Therapies

Zol­gens­ma patent spat brews be­tween No­var­tis and Re­genxbio as top No­var­tis gene ther­a­py ex­ec de­parts

Regenxbio, a small licensor of gene therapy viral vectors spun out from the University of Pennsylvania, is now finding itself in the middle of some major league patent fights.

In addition to a patent suit with Sarepta Therapeutics from last September, Novartis, is now trying to push its smaller partner out of the way. The Swiss biopharma licensed Regenxbio’s AAV9 vector for its $2.1 million spinal muscular atrophy therapy Zolgensma.

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