Sumit Aggarwal, Eloxx Pharmaceuticals president and CEO

Eloxx re­ports PhII cys­tic fi­bro­sis fail as the biotech weighs its op­tions

A rare dis­ease biotech has fall­en short in a clin­i­cal tri­al — and in­vestors are none too hap­py about it.

Eloxx Phar­ma­ceu­ti­cals re­port­ed Wednes­day that its small mol­e­cule can­di­date ELX-02 com­bined with iva­caftor failed a small Phase II tri­al. The com­bi­na­tion tri­al test­ed the two drugs in pa­tients with Class 1 cys­tic fi­bro­sis and at least one “non­sense mu­ta­tion.” Iva­caftor is one-half of Ver­tex’s cys­tic fi­bro­sis block­buster drug Orkam­bi.

Ac­cord­ing to Eloxx, the com­bo failed to see sta­tis­ti­cal sig­nif­i­cance on cer­tain ef­fi­ca­cy end­points, such as changes from base­line in sweat chlo­ride con­cen­tra­tion and per­fect forced ex­pi­ra­to­ry vol­ume.

How­ev­er, the biotech not­ed in an SEC fil­ing:

Ev­i­dence of ac­tiv­i­ty for ELX-02 was ob­served, as pa­tients with high­er base­line sweat chlo­ride lev­els demon­strat­ed in­creased re­spons­es as in­di­cat­ed by SCC (p=0.00013 at Day 35). Tri­al re­sults were po­ten­tial­ly con­found­ed by high vari­abil­i­ty in sweat chlo­ride and lung func­tion mea­sure­ment. The Com­pa­ny be­lieves this vari­abil­i­ty could have been caused by very low drug ex­po­sures in the lung.

Pres­i­dent and CEO Sum­it Ag­gar­w­al tells End­points News that Eloxx will be work­ing with the CF Foun­da­tion to de­ter­mine the next steps in ELX-02’s de­vel­op­ment. The or­ga­ni­za­tion had fi­nan­cial­ly backed Eloxx’s tri­al.

As for why the tri­al failed, the CEO said that ef­fi­ca­cy is not the same as ac­tiv­i­ty.

“We were mea­sur­ing lung func­tion im­prove­ment of func­tion­al re­sponse, not sim­ply ac­tiv­i­ty. So ac­tiv­i­ty can ex­ist but be drowned out by vari­abil­i­ty due to low drug ex­po­sure, pa­tient char­ac­ter­is­tics, such that you don’t that doesn’t trans­late in­to ef­fi­ca­cy in a sta­tis­ti­cal­ly sig­nif­i­cant way when you have on­ly 11 pa­tients in a tri­al,” Ag­gar­w­al said.

On that note, Ag­gar­w­al added that the com­pa­ny has al­ready start­ed putting to­geth­er a tri­al test­ing ELX-02 in eight pa­tients with Al­port syn­drome, a ge­net­ic con­di­tion char­ac­ter­ized by pro­gres­sive loss of kid­ney func­tion. The plan on that front is to have a read­out in the first half of 2023.

“With our re­sources, they’re much bet­ter spent on Al­port,” the chief ex­ec­u­tive not­ed.

The pen­ny stock play­er $ELOX fell 39% in ear­ly morn­ing trad­ing Thurs­day, down to 23 cents a share. The biotech was sub­ject to a delist­ing no­tice back in Jan­u­ary, say­ing that it has un­til Jan­u­ary 2, 2023, to get back in­to com­pli­ance with Nas­daq, es­sen­tial­ly get­ting its stock price back over a dol­lar for the first time since No­vem­ber.

Ag­gar­w­al tells End­points that in light of the low stock price, the biotech has enough cash to get it­self through Q4 of next year — and es­sen­tial­ly all op­tions, in­clud­ing a re­verse split, are on the ta­ble.

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

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

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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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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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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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.

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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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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