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.

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

Clay Siegall, Morphimmune CEO

Up­dat­ed: Ex-Seagen chief Clay Sie­gall emerges as CEO of pri­vate biotech

Clay Siegall will be back in the CEO seat, taking the helm of a private startup working on targeted cancer therapies.

It’s been almost a year since Siegall resigned from Seagen, the biotech he co-founded and led for more than 20 years, in the wake of domestic violence allegations by his then-wife. His eventual successor, David Epstein, sold the company to Pfizer in a $43 billion deal unveiled last week.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

Zhi Hong, Brii Biosciences CEO

Brii Bio­sciences stops man­u­fac­tur­ing Covid-19 an­ti­body com­bo, plans to with­draw EUA re­quest

Brii Biosciences said it will stop manufacturing its Covid-19 antibody combination, sold in China, and is working to withdraw its emergency use authorization request in the US, which it started in October 2021.

The Beijing and North Carolina biotech commercially launched the treatment in China last July but is now axing the work and reverting resources to other “high-priority programs,” per a Friday update. The focus now is namely hepatitis B viral infection, postpartum depression and major depressive disorders.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

Sergio Traversa, Relmada Therapeutics CEO

Rel­ma­da makes 'crit­i­cal changes' to PhI­II tri­al to try and save de­pres­sion drug

Relmada Therapeutics is making changes to its Phase III study of its lead drug for major depressive disorder, in an attempt to avoid problems with a prior trial that showed little difference between the drug and a placebo.

That failure in October wiped 80% from Relmada’s stock price, and was followed by another negative readout a few months later. In both cases, the company said that there had been trial sites that were associated with what it called surprising placebo effects that skewed the results compared with the drug, REL-1017.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

Peter Hecht, Cyclerion Therapeutics CEO

Hard pressed for cash, Cy­cle­ri­on looks for help fund­ing rare dis­ease drug

Cyclerion Therapeutics may have the design of a Phase IIb study ready to go, but it’s scrambling for a way to fund it.

The company said in a press release that it’s “actively evaluating the best combination of capital, capabilities, and transactions available to it to advance the development of zagociguat,” its lead candidate for a rare, genetic mitochondrial disease known as MELAS.

In a separate SEC filing, Cyclerion once again flagged “substantial doubt about (its) ability to continue as a going concern.” As of the end of 2022, it had cash and cash equivalents of only $13.4 million.

FDA ad­vi­sors unan­i­mous­ly rec­om­mend ac­cel­er­at­ed ap­proval for Bio­gen's ALS drug

A panel of outside advisors to the FDA unanimously recommended that the agency grant accelerated approval to Biogen’s ALS drug tofersen despite the drug failing the primary goal of its Phase III study, an endorsement that could pave a path forward for the treatment.

By a 9-0 vote, members of the Peripheral and Central Nervous System Drugs Advisory Committee said there was sufficient evidence that tofersen’s effect on a certain protein associated with ALS is reasonably likely to predict a benefit for patients. But panelists stopped short of advocating for a full approval, voting 3-5 against (with one abstention) and largely citing the failed pivotal study.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

Geoff McDonough, Generation Bio president and CEO

Mod­er­na part­ners on non-vi­ral gene ther­a­py with Gen­er­a­tion Bio af­ter swing­ing gene edit­ing deals

Moderna has inked a five-year partnership with gene therapy biotech Generation Bio, it announced Thursday morning, wading deeper into the genetic medicines space as it navigates beyond its vaccine work.

Moderna will pay Generation Bio $40 million upfront and invest another $36 million into the gene therapy biotech. In exchange, Moderna can license Generation Bio’s non-viral gene therapy platforms for two immune cell programs and two liver programs, with an option for a fifth program. Moderna will fund all the research work under the partnership, and could be on the hook for milestone, fee and royalty payments totaling up to $1.8 billion, a company spokesperson tells Endpoints News.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

Paul Song, NKGen Biotech CEO

NK cell ther­a­py-fo­cused biotech eyes SPAC deal

A small, Santa Ana-based biotech created in 2017 is looking to enter a SPAC deal as it lays out plans to begin trials in its lead cell therapy candidates and bring on new executives.

Graf Acquisition Corp. IV and NKGen Biotech announced Thursday, with few other details, that the two companies signed a non-binding letter of intent to “pursue a business combination.” Graf Acquisition II and III withdrew their IPOs last year.

In­cyte hit by CRL on ex­tend­ed-re­lease JAK tablets, mud­dy­ing plans for Jakafi fran­chise ex­pan­sion

The FDA has rejected Incyte’s extended-release formulation of ruxolitinib tablets, in a surprise setback for the company’s plans to build on its blockbuster Jakafi franchise.

The ruxolitinib XR tablets are designed to be taken once a day, whereas Jakafi is indicated for twice daily dosage (although some patients can take it once daily).

According to Incyte, the FDA acknowledged in its complete response letter that the study submitted in the NDA “met its objective of bioequivalence based on area under the curve (AUC) parameters but identified additional requirements for approval.”