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.”

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Pfiz­er's big block­buster Xel­janz flunks its post-mar­ket­ing safe­ty study, re­new­ing harsh ques­tions for JAK class

When the FDA approved Pfizer’s JAK inhibitor Xeljanz for rheumatoid arthritis in 2012, they slapped on a black box warning for a laundry list of adverse events and required the New York drugmaker to run a long-term safety study.

That study has since become a consistent headache for Pfizer and their blockbuster molecule. Last year, Pfizer dropped the entire high dose cohort after an independent monitoring board found more patients died in that group than in the low dose arm or a control arm of patients who received one of two TNF inhibitors, Enbrel or Humira.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 99,000+ biopharma pros reading Endpoints daily — and it's free.

Top gene ther­a­py deals, M&A pacts in 2020 high­light an­oth­er big year in one of the hottest fields in bio­phar­ma

Chris Dokomajilar at DealForma has been crunching the numbers on gene therapy deals over the last 2 years and came away with a few key observations.

Both the upfront cash and deal totals last year backed off a bit from the record high hit in 2019, but the totals are still running well ahead of anything we’ve seen in the years prior to 2019/2020.
2020 R&D partnerships came in at 23 deals, with $1.1 billion in disclosed upfront cash and equity and more than $8.5 billion in total deal value. Looking at 2019-2020 M&A, Dokomajilar found: 9 Acquisitions, with over $11.1 billion in disclosed upfront cash and equity and more than $13.4 billion in total M&A value.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 99,000+ biopharma pros reading Endpoints daily — and it's free.

Steve Harr (L) and Hans Bishop

One of the most am­bi­tious start­up teams in biotech just out­lined plans for a $400M IPO and a val­u­a­tion of about $4B

The executive team at Sana Biotechnology has sketched out more details about the full scope of its ambitions as the new unicorn to watch. They amended their S-1 today to include a price range of $20 to $23 a share — which puts them in reach of pulling in around $400 million on the high end with a market value starting right around $4 billion.

That’s not bad for a preclinical biotech with no drugs yet in human studies, but it squares with its ambitions to remake the cell therapy field with a slate of in-house platforms. The biotech raised $705 million — primarily from ARCH (44 million shares) and Flagship (34.2 million shares) — to get to this stage.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 99,000+ biopharma pros reading Endpoints daily — and it's free.

Bob Nelsen (Michael Kovac/Getty Images)

ARCH an­nounces largest fund yet, rais­ing $1.85B to back men­tal health, cell and gene edit­ing ap­proach­es

Nearly a year ago, as the pandemic encroached and the stock market cratered, Flagship and ARCH Venture announced three mega-funds worth a combined $2.6 billion. They wanted, ARCH’s Bob Nelsen said, to restore confidence “that there was money out there and a lot of it” to invest in biotech.

Since then, the stock market has returned — almost frighteningly so — and Nelsen has kept raising and spending cash. On Thursday, he announced a new fund, worth $1.85 billion. It’s the largest pot yet for a VC famous for its deep pockets.

Ther­mo Fish­er plat­form seeks to ex­pe­dite donor cell cul­ti­va­tion for al­lo­gene­ic cell ther­a­pies

One of the world’s leading CDMOs has launched a new technology it says will expedite a quickly-growing sect of biotech drug development: off-the-shelf, allogeneic cell therapies.

It’s been nearly a decade since the FDA approved the first use of the method that uses healthy donor cells to create a master cell bank, which is then used for specific therapies — a cord blood allogeneic treatment called Hemacord. In the years since, the use of allogeneic cells has taken off in research circles, most notably in the use of T cell therapies to target solid tumor cancers.

Take­da earns win for its TKI in­hibitor in tiny lung can­cer group — but GI side ef­fects could be an ear­ly red flag

Japanese drugmaker Takeda has made a big push in recent years to build a hand in oncology, particularly in the next-gen cancer space. One of those candidates, tyrosine kinase inhibitor (TKI) mobocertinib, recently earned the FDA’s interest in a small section of untreated lung cancer patients, but will severe GI side effects be a roadblock?

Takeda’s oral mobocertinib posted clinically significant objective response rates in a Phase I/II adaptive trial drugging metastatic non-small cell lung cancer patients with EGFR exon 20 gene mutations who had previously undergone platinum-based chemotherapy, according to data presented Thursday at the virtual World Conference on Lung Cancer.

Covid-19 roundup: EU and As­traZeneca trade blows over slow­downs; Un­usu­al unions pop up to test an­ti­bod­ies, vac­cines

After coming under fire for manufacturing delays last week, AstraZeneca’s feud with the European Union has spilled into the open.

The bloc accused the pharma giant on Wednesday of pulling out of a meeting to discuss cuts to its vaccine supplies, the AP reported. AstraZeneca denied the reports, saying it still planned on attending the discussion.

Early Wednesday, an EU Commission spokeswoman said that “the representative of AstraZeneca had announced this morning, had informed us this morning that their participation is not confirmed, is not happening.” But an AstraZeneca spokesperson later called the reports “not accurate.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 99,000+ biopharma pros reading Endpoints daily — and it's free.

Janet Woodcock (AP Images)

Ad­vo­ca­cy groups don't want Janet Wood­cock to head the FDA, blast­ing ‘reg­u­la­to­ry fail­ures’ in opi­oid cri­sis

It turns out the controversies around Janet Woodcock’s regulatory legacy weren’t limited to Sarepta’s eteplirsen.

A coalition of advocacy groups dedicated to the opioid crisis urged Norris Cochran and Xavier Becerra — the acting and designated HHS secretary, respectively — to keep her reign as interim FDA chief a “very short transition.” During her lengthy tenure as CDER, they add, Woodcock presided over “one of the worst regulatory agency failures in U.S. history.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 99,000+ biopharma pros reading Endpoints daily — and it's free.