FDA slams door to piv­otal tri­al for bub­ble boy dis­ease gene ther­a­py as Mus­tang Bio runs in­to an­oth­er hold

Mus­tang Bio is in fa­mil­iar ter­ri­to­ry, but that isn’t a place it nec­es­sar­i­ly wants to be.

The FDA has placed a hold on Mus­tang Bio’s piv­i­tol tri­al for its gene ther­a­py to treat pa­tients with bub­ble boy dis­ease, cit­ing is­sues sur­round­ing chem­istry, man­u­fac­tur­ing and con­trols clear­ance. It’s the sec­ond hold due to CMC is­sues the com­pa­ny has re­ceived in rough­ly 18 months.

An in­ves­ti­ga­tion­al new drug ap­pli­ca­tion was sub­mit­ted in De­cem­ber 2021. If grant­ed an IND, a Phase II study will then as­sess safe­ty, tol­er­a­bil­i­ty and ef­fi­ca­cy of MB-207. If ap­proved by the FDA, the ther­a­py would one day be el­i­gi­ble for a rare pe­di­atric dis­ease vouch­er.

The ther­a­py, known as MB-207, has been pre­vi­ous­ly grant­ed or­phan drug and rare pe­di­atric dis­ease des­ig­na­tions. The lentivi­ral ther­a­py is for those pa­tients who have al­ready been treat­ed with a hematopoi­et­ic stem cell trans­plan­ta­tion, and need more treat­ment.

Bub­ble boy dis­ease is of­fi­cial­ly known as X-linked se­vere com­bined im­mun­od­e­fi­cien­cy. It’s a rare ge­net­ic dis­or­der that oc­curs in 1 per 225,000 births, and is char­ac­ter­ized by the lack of func­tion of key im­mune cells. That leaves chil­dren with a se­vere­ly com­pro­mised im­mune sys­tem, and can lead to the ear­ly death of chil­dren. Many who are af­fect­ed by the dis­ease are un­able to es­tab­lish T cell im­mu­ni­ty.

Mus­tang was pre­vi­ous­ly is­sued a hold for MB-107, which is cur­rent­ly in Phase I/II tri­als at St Jude, UCSF Be­nioff Chil­dren’s Hos­pi­tal in San Fran­cis­co and Seat­tle Chil­dren’s Hos­pi­tal in new­ly di­ag­nosed in­fants un­der the age of two. In June 2021, the progress of MB-107 was de­layed, but about a year ago, the hold was cleared up, and reg­u­la­tors al­lowed the Phase II tri­al to pro­ceed af­ter re­ceiv­ing a com­pre­hen­sive pack­age on CMC that was sub­mit­ted in De­cem­ber 2020.

That tri­al en­rolled 10 pa­tients, and com­bined them with an­oth­er 15 al­ready treat­ed. Then, the 25 pa­tients will be com­pared with an­oth­er 25 pa­tients who “matched his­tor­i­cal con­trol pa­tients who have un­der­gone hematopoi­et­ic stem cell trans­plan­ta­tion.” Re­sults are ex­pect­ed from that in the sec­ond half of this year.

In a state­ment, CEO Manuel Litch­man said:

In light of our pos­i­tive ex­pe­ri­ence man­ag­ing the pri­or MB-107 CMC hold, and our abil­i­ty to se­cure FDA clear­ance to pro­ceed with that pro­gram, we be­lieve that our CMC team is well po­si­tioned to ad­dress the agency’s con­cerns around MB-207 once ad­di­tion­al clar­i­fi­ca­tion of the hold be­comes avail­able. Fur­ther­more, we re­main ful­ly com­mit­ted to the suc­cess of the piv­otal Phase II MB-207 clin­i­cal tri­al for chil­dren with XS­CID who have pre­vi­ous­ly re­ceived HSCT and re­quire re-treat­ment.

The news comes a lit­tle more than a month af­ter the com­pa­ny joined the NAS­DAQ. The stock hov­ered around the usu­al dol­lar-and-change mark Tues­day, as it sat around $1.17 per share around 11 a.m.

Jean-Paul Clozel, Idorsia CEO (Patrick Straub/Keystone via AP Images)

Idor­si­a's brain bleed drug flunks PhI­II tri­al, a decade af­ter pre­vi­ous flop

Idorsia’s long journey with clazosentan came to an abrupt “unexpected result” Monday morning with a Phase III flop.

The Swiss biopharma said the drug did not meet the main goal of the late-stage REACT study, conducted in the US, Canada and Europe since early 2019.

The 409-patient trial tested the intravenous drug’s ability to prevent complications due to delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage (aSAH), in which blood vessels in the brain narrow and blood accumulates around the brain’s surface, which then dials up the pressure on the brain.

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Kenji Yasukawa, Astellas CEO (Photographer: Akio Kon/Bloomberg via Getty Images)

Astel­las taps chief strat­e­gy of­fi­cer as next CEO to 'go on the ag­gres­sive'

Five years into its big R&D revamp, Astellas says it’s time for a changing of the guard.

Kenji Yasukawa, who took over as president and CEO in 2018, will step down to become chairman of the board in April, making room for Naoki Okamura to take over. Okamura joined the company in 1986 and has served in a variety of finance, business and strategy roles, including most recently as chief strategy officer.

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Clin­i­cal tri­al di­ver­si­ty da­ta show mis­match be­tween en­roll­ment and dis­ease preva­lence, GSK says

A lack of diversity in clinical trials has persisted despite decades of initiatives to try to turn the tide.

In a recent review of 17 years of clinical trials, drugmaker GSK found that there were some mismatches between the demographics of its US-based trials and how prevalent diseases were in those populations.

The results, the company says, will help GSK and others design studies that better represent epidemiological rates within races and ethnicities.

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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Uğur Şahin, BioNTech CEO (Andreas Arnold/picture-alliance/dpa/AP Images)

BioN­Tech opens new plas­mid DNA man­u­fac­tur­ing fa­cil­i­ty in Ger­many

German mRNA player BioNTech opened the doors to a new manufacturing facility on Thursday, this one just about 75 miles north of its headquarters in Mainz, Germany.

BioNTech announced on Thursday that it has completed the construction of its first plasmid DNA manufacturing facility in Marburg, Germany. The facility will produce materials for mRNA-based vaccines and therapies along with cell therapies.

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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David Kirn, 4D Molecular Therapeutics CEO (via website)

FDA places hold on 4D Mol­e­c­u­lar’s Fab­ry gene ther­a­py

4D Molecular Therapeutics quietly tucked an FDA clinical hold on its Fabry gene therapy into an SEC filing.

Meanwhile, the biotech issued a press release the same day after the closing bell on Thursday touting an IND for another asset, in diabetic macular edema.

The California biotech had paused enrollment of patients in its two trials of the Fabry gene therapy (4D-310) last month after three patients experienced kidney issues, all of which were resolved within four weeks. At the time, 4DMT said it would wait until the second half of this year to look at 12-month clinical data on six patients in the Phase I/II trials, one in the US and one in Taiwan and Australia.

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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.

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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