Craig Cohen, Bixby Center UCSF

Ex­per­i­men­tal in­jec­tion of 'good' bac­te­ria sig­nif­i­cant­ly cut bac­te­r­i­al vagi­nosis re­cur­rence rate — study

Bac­te­r­i­al vagi­nosis (BV), an in­flam­ma­to­ry con­di­tion caused by the pro­lif­er­a­tion of “bad” bac­te­ria nat­u­ral­ly found in the vagi­na, can af­fect up to half the women of re­pro­duc­tive age world­wide. De­spite treat­ment with an­tibi­otics, up to three in four women get re­cur­rent in­fec­tions with­in three months. But in­ject­ing a ‘good’ bac­teri­um to sub­due its dele­te­ri­ous peers can slash that high re­cur­rence rate by a third, new clin­i­cal tri­al da­ta sug­gest.

A 228-pa­tient, place­bo-con­trolled study fund­ed by the NIH eval­u­at­ed the ef­fect of a ‘good’ bac­teri­um prod­uct, called Lactin-V, which was pack­aged by Cal­i­for­nia-based mi­cro­bio­me com­pa­ny Os­el. The prod­uct, which is for­mu­lat­ed as a pow­der con­tain­ing a strain of the bac­teri­um Lac­to­bacil­lus crispa­tus, was in­ject­ed in­to the vagi­na us­ing a plas­tic de­vice that re­sem­bles a tam­pon ap­pli­ca­tor — af­ter pa­tients were treat­ed with a course of the an­tibi­ot­ic metron­ida­zole in gel form.

At the three month mark, BV re­cur­rence oc­curred in 46 par­tic­i­pants (30%) in the Lactin-V group and in 34 par­tic­i­pants (45%) in the place­bo group (con­fi­dence in­ter­val: 0.44 to 0.87; P=0.01) — meet­ing the main goal of the study. At week 24, there were 27% few­er cas­es of BV among those who got Lactin-V. No ev­i­dence emerged sug­gest­ing that Lactin-V caus­es any lo­cal or sys­temic side ef­fects.

This is re­al­ly the first ma­jor break­through in the field, pro­vid­ing ad­ju­vant treat­ment as an op­tion for women suf­fer­ing from re­cur­rent BV, if we can con­firm the find­ings in a de­fin­i­tive piv­otal phase III tri­al, the study’s lead in­ves­ti­ga­tor Craig Co­hen, a pro­fes­sor of ob­stet­rics, gy­ne­col­o­gy and re­pro­duc­tive sci­ences at the Uni­ver­si­ty of Cal­i­for­nia, San Fran­cis­co, told End­points News. 

Oth­er ef­forts, such as fe­cal trans­plants for C. dif­fi­cile, have bet on en­tire mi­cro­bial com­mu­ni­ties to fight stub­born in­fec­tions, he not­ed. “So for a sin­gle strain, to my knowl­edge, this may be the first live bio­ther­a­peu­tic to demon­strate ef­fi­ca­cy.”

Tri­al da­ta al­so showed that among women who in­ject­ed Lactin-V, L. crispa­tus bac­teri­um was de­tect­ed in 79% of women at week 12 and 48% at week 24. In the place­bo group, the bac­teri­um was found in 6% of women dur­ing week 12 and 2% at week 24.

“Al­though com­bi­na­tion metron­ida­zole–pro­bi­ot­ic reg­i­mens have been test­ed pre­vi­ous­ly and some have been shown to re­duce the risk of re­cur­rence of bac­te­r­i­al vagi­nosis, the tri­als have gen­er­al­ly been small and have lacked the use of stan­dard­ized meth­ods, in­clud­ing ob­jec­tive out­come mea­sures for bac­te­r­i­al vagi­nosis re­cur­rence and col­o­niza­tion by the ac­tive tri­al med­ica­tion,” the re­searchers wrote in the New Eng­land Jour­nal of Med­i­cine, where the study was pub­lished on Wednes­day.

The study was fund­ed by the NIH, al­though Os­el pro­vid­ed Lactin-V, which is al­so be­ing test­ed as a treat­ment for re­cur­rent uri­nary tract in­fec­tions, in vit­ro fer­til­iza­tion and preterm birth by the com­pa­ny. A late-stage BV tri­al is al­so be­ing planned by Os­el, pend­ing dis­cus­sions with the FDA.

“We think this is a re­al­ly im­por­tant land­mark in the field, it’s the first study to re­al­ly show with a rig­or­ous­ly con­duct­ed tri­al, a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion (in BV re­cur­rence rates). We al­so have been able to show the re­la­tion­ship be­tween mi­cro­bio­ta and pre­ven­tion of BV re­cur­rence, which in the past is some­thing that in the mi­cro­bio­me field has been sort of in the realm of as­so­ci­a­tions,” said Tom Parks, Os­el’s di­rec­tor of prod­uct de­vel­op­ment said in an in­ter­view.

“So we’re putting a causal re­la­tion­ship to­geth­er here to show that mi­cro­bio­ta can be im­pact­ed by the in­tro­duc­tion of an ex­oge­nous lac­to­bacil­lus.”

The al­lure of L. crispa­tus

Lactin-V con­tains Lac­to­bacil­lus crispa­tus, a strain of bac­te­ria that has long known to be a ben­e­fi­cial com­po­nent of the vagi­nal mi­cro­bio­me by pri­mar­i­ly pro­duc­ing lac­tic acid. The re­sult­ing low pH con­sti­tutes a strong de­ter­rent against the over­growth of op­por­tunis­tic pathogens. Da­ta al­so sug­gest that these lac­to­bacil­lus species are strong­ly as­so­ci­at­ed with re­pro­duc­tive health, full-term birth and com­bat­ing sex­u­al­ly trans­mit­ted in­fec­tions.

In a re­cent study led by Jacques Rav­el, who serves as the co-ed­i­tor-in-chief of the jour­nal Mi­cro­bio­me, found that the di­ver­si­ty of L. crispa­tus strains is in the re­gion of 5,000. That find­ing, Rav­el ex­plained in a pre­vi­ous in­ter­view with End­points News, has ma­jor im­pli­ca­tions.

“From one woman to an­oth­er, they might car­ry that same species, but it’s of­ten not the same strain,” he said.

“What this means is that this con­cept of one strain solv­ing all the prob­lems is kind of gone. And that each woman ac­tu­al­ly has a mi­cro­bio­me, even though it’s dom­i­nat­ed by a species, that species is rep­re­sent­ed by many, many dif­fer­ent strains. So it’s al­most like a lit­tle con­sor­tium of strains that are to­geth­er — from the same species — but those strains work to­geth­er in pro­vid­ing dif­fer­ent func­tions. The whole con­sor­tium of all those strains to­geth­er makes them stronger.”

When Os­el start­ed work­ing on Lactin-V, sci­en­tists didn’t have the tools to in­ter­ro­gate the vagi­nal mi­cro­bio­me as they have now, Co­hen said, adding that the strain of L. crispa­tus used in the prod­uct was tak­en from an African Amer­i­can woman in Seat­tle (BV has a rel­a­tive­ly high­er preva­lence in women of col­or).

This tri­al da­ta on Lactin-V “been a long time com­ing,” Parks said, ex­plain­ing that the strain the com­pa­ny chose was de­ter­mined by a num­ber of fac­tors in­clud­ing its abil­i­ty to latch on vagi­nal ep­ithe­lial cells and pro­duce lac­tic acid.

“We’re hop­ing that this will ba­si­cal­ly put the vagi­nal mi­cro­bio­me on the map and lead to more and im­proved treat­ments for fe­male re­pro­duc­tive health pur­pos­es.”

Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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In his­toric Covid-19 ad­comm, vac­cine ex­perts de­bate a sea of ques­tions — but of­fer no clear an­swers

The most widely anticipated and perhaps most widely watched meeting in the FDA’s 113-year history ended late Thursday night with a score of questions and very few answers.

For nearly 9 hours, 18 different outside experts listened to public health agencies and foundations present how the United States’ Covid-19 vaccine program developed through October, and they debated where it should go from there: Were companies testing the right metrics in their massive trials? How long should they track patients before declaring a vaccine safe or effective? Should a vaccine, once authorized, be given to the volunteers in the placebo arm of a trial?

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A top drug pro­gram at Bay­er clears a high bar for CKD — open­ing the door to an FDA pitch

Over the past 4 years, Bayer has been steering a major trial through a pivotal program to see if their drug finerenone could slow down the pace of chronic kidney disease in patients suffering from both CKD as well as Type 2 diabetes.

Today, their team jumped on a virtual meeting hosted by the American Society of Nephrology to offer a solid set of pivotal data to demonstrate that the drug can delay dialysis or a kidney replacement as well as cardio disease, while also adding some worrying signs of hyperkalemia among the patients taking the drug. And they’re hustling it straight to regulators in search of an approval for kidney disease and cardio patients — one of the toughest challenges in the book, as demonstrated by repeated past failures.

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Biond­Vax stock im­plodes af­ter a big PhI­II gam­ble for its uni­ver­sal flu vac­cine fails

After flying high on Wall Street for the last few months of a pandemic, BiondVax’s stock and dreams of getting approval for its universal flu vaccine hit the windshield.

The Jerusalem-based biotech announced on Friday that its only clinical candidate, M-001, failed both primary and secondary endpoints in a Phase III study. There was no statistically significant difference in reduction of flu illness and severity between the vaccine and placebo groups, according to the company. The vaccine did prove safe, if ineffective, BiondVax said.

Pascal Soriot, AstraZeneca CEO (Zach Gibson/Bloomberg via Getty Images)

UP­DAT­ED: FDA gives As­traZeneca the thumbs-up to restart PhI­II Covid-19 vac­cine tri­als, and J&J is prepar­ing to re­sume its study

Several countries had restarted their portions of AstraZeneca’s global Phase III Covid-19 vaccine trial after the study was paused worldwide in early September, but the US notably stayed on the sidelines — until now. Friday afternoon the pharma giant announced the all clear from US regulators. And on top of that, J&J announced Friday evening that it’s preparing to resume its own Phase III vaccine trial.

Ul­tragenyx in­jects $40M to grab Solid's mi­crody­s­trophin trans­gene — while side­step­ping the AAV9 vec­tor that stirred up safe­ty fears

Since before Ilan Ganot started Solid Bio to develop a gene therapy for kids like his son, who has Duchenne muscular dystrophy, Ultragenyx CEO Emil Kakkis has been watching and advising the former investment banker as he navigated the deep waters of drug development.

Just as Solid is getting back up on its feet after a yearlong clinical hold, Kakkis has decided to jump in for a formal alliance.

With a $40 million upfront, Ultragenyx is grabbing 14.45% of Solid’s shares $SLDB and the rights to its microdystrophin construct for use in combination with AAV8 vectors. Solid’s lead program, which utilizes AAV9, remains unaffected. The company also retains rights to other applications of its transgene.

Adam Koppel and Jeffrey Schwartz, Bain

Bain ex­ecs Adam Kop­pel and Jef­frey Schwartz line up $125M for their first blank check deal as Wall Street con­tin­ues to em­brace biotech

Adam Koppel and Jeffrey Schwartz have jumped into the blank check game, raising $125 million for a stock listing in search of a company.

Their SPAC, BCLS Acquisition Corp, raised $125 million this week, with a line on $25 million more as it scouts for a biotech in search of money and a place on Wall Street.

The two principals at Bain Life Sciences have been on a romp since they set up the Bain operation 4 years ago. Their S-1 spells out a track record of 22 deals totaling $650 million for the life sciences group, which led to 9 IPOs.

Covid-19 roundup: An mR­NA play­er gets a boost out of the lat­est round of an­i­mal da­ta; Phase­Bio pulls the plug on treat­ment tri­al

The big tell for CureVac $CVAC is coming up with a looming early-stage readout on their mRNA Covid-19 vaccine in the clinic. But for now they’ll make do with an upbeat assessment on the preclinical animal data they used to get into the clinic.

Researchers for the German biotech say they got the high antibody titers and T cell activation they were looking for, lining up a hamster challenge to demonstrate — in a simple model — that the vaccine could protect the furry creatures. Like the other mRNA vaccines, the drug sends instructions to spur cells to decorate themselves with the distinctive spike on the virus to elicit an immune response.

Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

Setting the stage for an extraordinary one-day meeting of the Vaccines and Related Biological Products Advisory Committee this Thursday, the FDA has cleared 2 experts of financial conflicts to help beef up the committee. And regulators went on to specify the safety, efficacy and CMC input they’re looking for on EUAs, before they move on to the full BLA approval process.

All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

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