Bob Azelby, Eliem Therapeutics CEO

Eliem de­lays a de­pres­sion tri­al, in­def­i­nite­ly post­pones an­oth­er af­ter blam­ing CMC is­sues for low drug ex­po­sure

In the drug R&D world, plans are not set in stone, as Eliem Ther­a­peu­tics ex­hib­it­ed Mon­day with shifts to its de­pres­sion strat­e­gy.

The Seat­tle-UK biotech orig­i­nal­ly want­ed to start two mid-stage de­pres­sion tri­als this year but will have to de­lay one — in ma­jor de­pres­sive dis­or­der — un­til next year and in­def­i­nite­ly post­pone the oth­er in per­i­menopausal de­pres­sion. Back in April, Eliem de­layed the launch­es of both Phase IIa tri­als be­cause the biotech was cu­ri­ous as to why the ex­po­sure was low­er than ex­pect­ed in a Phase Ib study, which tried to prove out the con­cepts of ETX-155 in pho­to­sen­si­tive epilep­sy.

Now, with re­sults from an ini­tial re­view, the biotech thinks cer­tain parts of the CMC are “most like­ly” to blame for the re­duced ex­po­sure lev­els. The com­pa­ny thinks there might have been dif­fer­ences be­tween the batch­es of drug used in Phase I tri­als and the Phase Ib PSE study.

With that in­fo in hand, Eliem will take the GABAa pos­i­tive al­losteric mod­u­la­tor through an­oth­er Phase I phar­ma­co­ki­net­ic tri­al us­ing the drug batch­es that were used in the PSE study. The biotech plans to find out which dose will pro­vide a sim­i­lar ex­po­sure to the 60 mg dose used in the 14-day re­peat dose healthy vol­un­teer study pre­vi­ous­ly con­duct­ed.

Re­sults from that tri­al are slat­ed for the fourth quar­ter, and then a ran­dom­ized, place­bo-con­trolled Phase IIa in MDD pa­tients will kick off the first quar­ter of the new year. The mid-stage tri­al will test the drug as a four-week treat­ment, with topline da­ta to come through in mid-2024.

Mean­while, the oth­er de­pres­sion tri­al is be­ing post­poned to “pro­vide ad­di­tion­al in­vest­ment flex­i­bil­i­ty for the pro­gres­sion of Eliem’s pipeline,” the biotech said Mon­day. Eliem will con­sid­er re­sum­ing the Phase Ib PSE tri­al af­ter the phar­ma­co­ki­net­ic study lat­er this year.

“We are en­cour­aged by the prece­dent val­i­da­tion of the GABAA PAM class in mul­ti­ple large de­pres­sion tri­als and be­lieve ETX-155 has the po­ten­tial to be a clin­i­cal­ly dif­fer­en­ti­at­ed GABAA PAM prod­uct can­di­date,” Eliem CEO and pres­i­dent Bob Azel­by said in a state­ment.

Eliem is among a crop of bio­phar­mas at­tempt­ing to get a new MDD drug across the fin­ish line, with Ax­some re­port­ing its long-de­layed shot is back up for la­bel­ing dis­cus­sions at the FDA. Xenon, Prax­is and Bio­gen and Sage are among oth­ers in the field. Prax­is’s drug failed to pass muster in a Phase II/III study last month.

The de­pres­sion news comes weeks, or a few months at most, be­fore Eliem will pro­vide an up­date on its oth­er clin­i­cal-stage as­set, ETX-810. The pro­drug failed a mid-stage study in April in pa­tients with di­a­bet­ic pe­riph­er­al neu­ro­path­ic pain, but an­oth­er Phase II study is slat­ed to read out this quar­ter in pa­tients with lum­bosacral radic­u­lar pain, or sci­at­i­ca.

The Big Phar­ma dis­card pile; Lay­offs all around while some biotechs bid farewell; New Roche CEO as­sem­bles top team; and more

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With earnings seasons in full swing, we’ve listened in on all the calls so you don’t have to. But news is popping up from all corners, so make sure you check out our other updates, too.

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Trodelvy notch­es a win in most com­mon form of breast can­cer

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

Ma­gen­ta halts stem cell work and may sell it­self fol­low­ing pa­tient death, clin­i­cal hold

Magenta Therapeutics said it is halting work on its stem cell transplant drug pipeline and may sell itself, a week after the company reported the death of a patient in an early stage trial of its antibody-drug conjugate.

The Cambridge, MA-based company said it will conduct a “review of strategic alternatives,” and that could include an “acquisition, merger, business combination, or other transaction.”

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Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

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Sanofi scraps PhI­II tri­al for Prin­cip­ia drug af­ter re­view­ing com­pe­ti­tion

Months after the FDA placed Phase III trials of Sanofi’s BTK inhibitor on hold, the company is winding down one of the studies.

Sanofi reported in its Q4 earnings that the URSA study “was discontinued after careful evaluation of the emerging competitive treatment landscape in” myasthenia gravis, a rare disease that causes muscle weakness.

The Phase III, placebo-controlled trial was testing tolebrutinib in patients with the moderate-to-severe form of the disease. It started in late 2021, according to records on clinicaltrials.gov, and was originally designed to recruit 154 participants who were receiving the standard of care.

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Raymond Stevens, Structure Therapeutics CEO

Be­hind Fri­day's $161M IPO: A star sci­en­tist, GPCR drug dis­cov­ery and a plan to chal­lenge phar­ma in di­a­betes

What does it take to pull off a $161 million biotech IPO these days?

In Structure Therapeutics’ case, it means having a star scientist co-founder paired with the computational drug discovery company Schrödinger, $198 million in private funding from blue-chip investors, almost six years of research work on G protein-coupled receptors and a slate of oral, small-molecule drugs, with an eye on the huge and growing diabetes and weight-loss market.

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Af­ter 13 years, Ramy Mah­moud steps in­to CEO seat at Opti­nose; Ru­pert Vessey set to ex­it Bris­tol My­ers in Ju­ly

After 13 years as president and COO at Optinose, Ramy Mahmoud has stepped into a new role as its CEO. He is taking the place of Peter Miller, who stepped down earlier this week, though Miller is still staying with the company as a consultant.

In 2010, the two business partners joined Optinose to take it in a new direction, transforming it from a delivery platform to product company. They previously worked together at Johnson & Johnson, when Miller was president at Janssen and Mahmoud headed medical affairs. Miller said after he learned about Optinose, “I did what I always do, which is find people smarter than me to talk with about the idea. And the first person I called was Ramy … and I said, ‘Hey, Ramy, what do you think of this technology?’”

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How to use ex­ter­nal con­trols: FDA spells out think­ing in new draft guid­ance

The use of real-world evidence to inform the FDA’s decision-making continues apace, with the agency releasing new draft guidance yesterday on how sponsors can compare outcomes of trial participants receiving a test treatment with outcomes in a group of people external to the trial.

The practice of externally controlled trials is common, particularly in oncology or other difficult areas where it’s not ethical or feasible to use internal controls.

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The Big Phar­ma axe: Mer­ck cuts chikun­gun­ya vax, Bris­tol My­ers drops Cy­tomX-part­nered pro­gram, and more

As fourth quarter earnings come in, Big Pharmas are disclosing changes to their pipelines during their investor calls, and sometimes more quietly in presentation appendices.

Merck dropped its chikungunya vaccine candidate, which completed a Phase II study. Merck acquired the vaccine through its purchase of Themis Bioscience in 2020. In developing a vaccine for chikungunya, a mosquito-borne virus, Valneva is the frontrunner, as it submitted its vaccine to the FDA at the end of December.

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