Neb­u­liz­er fails PhII COPD study, but Verona plans to march on

Billed as the first new class of bron­chodila­tor in more than four decades, Verona Phar­ma’s $VR­NA ex­per­i­men­tal neb­u­liz­er did not con­fer sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment on a mea­sure of lung func­tion in Phase II study in­volv­ing pa­tients with chron­ic ob­struc­tive pul­monary dis­ease (COPD) who were al­ready on in­haled long-act­ing bron­chodila­tors.

Verona has tout­ed the drug, known as en­sifen­trine or RPL554, as the first po­ten­tial ther­a­py for res­pi­ra­to­ry dis­eases that acts as both a bron­chodila­tor and an­ti-in­flam­ma­to­ry agent in a soli­tary com­pound. Two dos­es of the drug in a neb­u­lized for­mu­la­tion were be­ing test­ed in the three-day, place­bo-con­trolled tri­al as a main­te­nance treat­ment for 79 COPD pa­tients, who were al­ready on com­mon­ly used LAMA/LA­BA treat­ments.

Pa­tients re­ceived three days of treat­ment with each of two dose strengths (1.5 mg or 6 mg) of neb­u­lized en­sifen­trine or place­bo twice dai­ly. The pri­ma­ry end­point was im­prove­ment in lung func­tion with en­sifen­trine, as mea­sured by FEV1 (forced ex­pi­ra­to­ry vol­ume in one sec­ond), a stan­dard mea­sure of res­pi­ra­to­ry func­tion, four hours post-dose af­ter the morn­ing dose on day three.

Jan-An­ders Karls­son

The pri­ma­ry end­point of FEV1 was not found to be sta­tis­ti­cal­ly sig­nif­i­cant af­ter the morn­ing dose, al­though the small­er en­sifen­trine dose im­proved peak FEV1, the com­pa­ny said, adding that the im­prove­ment was main­tained through­out the 24-hour pe­ri­od on day 3. The com­pa­ny’s shares slumped about 36% in mid­day trad­ing.

How­ev­er, da­ta on sec­ondary end­points in­clud­ing peak FEV1 over time and re­duc­tions in resid­ual vol­ume were en­cour­ag­ing: Peak FEV1 af­ter evening dose on day 3 showed sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment with both dos­es, and sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tions in mean resid­ual vol­ume were ob­served 15 min­utes fol­low­ing the evening dose on day 3, the Lon­don-based com­pa­ny said.

Over­all, the high­er dose did not re­sult in greater im­prove­ment in lung func­tion as com­pared with the 1.5 mg dose.

But Verona struck an up­beat tone. “Hav­ing demon­strat­ed in pre­vi­ous stud­ies the po­ten­tial of en­sifen­trine to de­liv­er ben­e­fits to pa­tients on no or sin­gle bron­chodila­tor ther­a­py, we be­lieve that this short study con­tin­ues to sup­port our view that en­sifen­trine may al­so be of ben­e­fit to more se­vere COPD pa­tients on dual and triple ther­a­py, for whom there are few oth­er treat­ment op­tions,” said Verona chief Jan-An­ders Karls­son in a state­ment.

“While we are dis­ap­point­ed that this ex­plorato­ry Phase 2 study did not achieve sta­tis­ti­cal sig­nif­i­cance for its pri­ma­ry end­point, these da­ta give us clar­i­ty on the de­sign…for fu­ture long-term stud­ies.”

Sun­Trust Robin­son Humphrey’s Ed­ward Nash ap­peared to agree with the com­pa­ny’s as­sess­ment, say­ing that the tri­al’s main goal was not met due to an un­ex­pect­ed­ly high­er place­bo ef­fect – oth­er­wise the drug did show im­proved FEV1 on top of dual/triple ther­a­py in a very chal­leng­ing COPD pa­tient pop­u­la­tion.

“We be­lieve the FDA would wel­come the low­er dose from a safe­ty stand­point and be­lieve to­tal­i­ty of da­ta which in­cludes ~104mL and 127mL im­prove­ment on top of monother­a­py (tiotropi­um) back­ground and 40mL to 50mL FEV1 im­prove­ments seen in dual/triple back­ground ther­a­py re­port­ed to­day pro­vides a pos­i­tive clin­i­cal and com­mer­cial pro­file for en­sifen­trine.”

Of the pa­tients treat­ed with dual bron­chodila­tor (LAMA/LA­BA) and triple ther­a­py (LAMA/LA­BA/ICS), re­search sug­gests that up to 40% (ap­prox­i­mate­ly 800,000 pa­tients in the US alone) are un­con­trolled, re­main­ing symp­to­matic and at an in­creased risk of ex­ac­er­ba­tions, ac­cord­ing to Verona.

Da­ta have sug­gest­ed that en­sifen­trine is an ef­fec­tive ad­di­tion to sin­gle bron­chodila­tors. The com­pa­ny is cur­rent­ly con­duct­ing a Phase II tri­al to eval­u­ate a dry pow­der in­haler for­mu­la­tion of en­sifen­trine for the same pa­tient pop­u­la­tion, and plans to test en­sifen­trine in a me­tered-dose in­haler for­mu­la­tion in pa­tients with COPD. In ad­di­tion, the drug is al­so be­ing test­ed for use in cys­tic fi­bro­sis and asth­ma.

Biotech and Big Phar­ma: A blue­print for a suc­cess­ful part­ner­ship

Strategic partnerships have long been an important contributor to how drugs are discovered and developed. For decades, big pharma companies have been forming alliances with biotech innovators to increase R&D productivity, expand geographical reach and better manage late-stage commercialization costs.

Noël Brown, Managing Director and Head of Biotechnology Investment Banking, and Greg Wiederrecht, Ph.D., Managing Director in the Global Healthcare Investment Banking Group at RBC Capital Markets, are no strangers to the importance of these tie-ups. Noël has over 20 years of investment banking experience in the industry. Before moving to the banking world in 2015, Greg was the Vice President and Head of External Scientific Affairs (ESA) at Merck, where he was responsible for the scientific assessment of strategic partnership opportunities worldwide.

No­var­tis' sec­ond at­tempt to repli­cate a stun­ning can­cer re­sult falls flat

Novartis’ hopes of turning one of the most surprising trial data points of the last decade into a lung cancer drug has taken another setback.

The Swiss pharma announced Monday that its IL-1 inhibitor canakinumab did not significantly extend the lives or slow the disease progression of patients with previously untreated locally advanced or metastatic non-small cell lung cancer when compared to standard of-care alone.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,600+ biopharma pros reading Endpoints daily — and it's free.

NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

Robert Califf (Pablo Martinez Monsivais, AP Images, File)

As buzz on Califf FDA nom heats up, in­dus­try and agency in­sid­ers of­fer a strong nod for the ‘per­fect’ choice

For once in this long, dramatic road to finding a new FDA commissioner, there’s been some continuity. Both CNN and Politico reported this weekend that Rob Califf met with President Biden to discuss the permanent commish role, following earlier news broken by the Washington Post that all signs point to Califf.

Although there may be a few Democrats who continue to grandstand about the dangers of COI (Califf has worked for Verily, sits on the board of Centessa Pharmaceuticals, and has other ties to industry research), with the pandemic ongoing and the need for some kind of continuity at FDA mounting, Califf is likely to meet the same fate as when he first won Senate confirmation in 2016, by a vote of 89-4 — Bernie Sanders and 6 others didn’t vote.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,600+ biopharma pros reading Endpoints daily — and it's free.

AstraZeneca CEO Pascal Soriot (Raphael Lafargue/Abaca/Sipa USA)

A com­bo of As­traZeneca's Imfinzi and chemo wins where oth­ers have failed in piv­otal bil­iary tract test

Looking to run with the big dogs in the PD-(L)1 class, AstraZeneca’s Imfinzi has a tall hill to climb to compete in an increasingly bustling market. An aggressive combo strategy for the drug has paid off so far, and now AstraZeneca is adding another notch to its belt.

A combo of Imfinzi (durvalumab) and chemotherapy significantly extended the lives of first-line patients with advanced biliary tract cancer over chemo alone, according to topline results from the Phase III TOPAZ-1 study revealed Monday.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,600+ biopharma pros reading Endpoints daily — and it's free.

Sean Ianchulev, Eyenovia CEO and CMO

Re­cent court de­ci­sion push­es FDA to re­ject and re­clas­si­fy drug-de­vice com­bo, crush­ing shares

Back in April, the FDA lost a crucial court case in which its broad discretion of regulating medical products that might satisfy the legal definitions of either “drug” and/or “medical device” was sharply curtailed.

In addition to the appeals court ruling that Genus Medical Technologies’ contrast agent barium sulfate (aka Vanilla SilQ) should not be considered a drug, as the FDA had initially ruled, but as a medical device, the agency also was forced to spell out which drugs would transition to devices as a result of the ruling.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,600+ biopharma pros reading Endpoints daily — and it's free.

Joan Butterton, Merck Research Laboratories VP of global clinical development, infectious diseases (Merck)

Mer­ck­'s ex­per­i­men­tal HIV drug is­la­travir hits with a PhI­II com­bo win and FDA fil­ing plans

Back in March, Merck and Gilead agreed to a partnership to challenge GlaxoSmithKline on long-acting HIV meds — by combining one drug from both Merck and Gilead that had shown potential. While Gilead brought its capsid inhibitor lenacapavir, Merck brought islatravir into the deal — a small molecule that the pharma acquired in 2012 from a small Japanese firm.

While that partnership is ongoing, islatravir is coming out of 2 Phase III pivotal trials with back-to-back successes and plans to beat a quick advance to the FDA.

Gil Beyen, Erytech CEO

A transat­lantic biotech flags a painful PhI­II can­cer flop, wav­ing a white flag

More than 4 years after little Erytech inflated some rare passion for its stock with upbeat Phase IIb data for their lead drug in pancreatic cancer, they’ve let the air out of the party balloons.

The transatlantic biotech $ERYP put the word out Monday morning that its drug eryaspase flopped in a Phase III pivotal for second line metastatic pancreatic cancer, slamming its stock, which plunged more than 30%.

Preston Klassen, Metacrine CEO

An­oth­er NASH play­er re­treats from bat­tered field af­ter tox­i­col­o­gy study flags po­ten­tial de­lay

NASH, the notorious liver disease afflicting an increasing number of Americans, has always been the focus at Metacrine ever since serial entrepreneur Rich Heyman unveiled the first round of financing all the way back in 2015.

Not anymore.

The San Diego-based biotech is halting its NASH program and choosing instead to prioritize its effort in pushing the same FXR agonist, MET642, into a Phase II trial for inflammatory bowel disease.