Gene ther­a­py for 'bub­ble boy dis­ease' sets stage for cure

In­fants with a rare, life-threat­en­ing ge­net­ic dis­or­der that ren­ders their im­mune sys­tem ob­so­lete may have a new lease on life, af­ter eight pa­tients with “bub­ble boy dis­ease” saw their body’s de­fense sys­tem re­stored by a gene ther­a­py de­vel­oped by sci­en­tists at the Na­tion­al In­sti­tutes of Health and St. Jude Chil­dren’s Re­search Hos­pi­tal in Mem­phis, Ten­nessee.

The con­di­tion — called X-linked se­vere com­bined im­mun­od­e­fi­cien­cy (SCID) — al­most ex­clu­sive­ly oc­curs in boys and is caused by mu­ta­tions in the IL2RG gene, which is in charge of mak­ing sure a pro­tein that is vi­tal for the growth and mat­u­ra­tion of de­vel­op­ing im­mune cells called lym­pho­cytes is pro­duced. With­out func­tion­ing lym­pho­cytes, which de­fend the body against pathogens, make an­ti­bod­ies, and help reg­u­late the im­mune sys­tem, the small­est in­fec­tions such as the com­mon cold can be fa­tal.

A bone mar­row trans­plant — though med­ical­ly risky — from a ge­net­i­cal­ly-matched sib­ling can be cu­ra­tive, but pa­tients don’t al­ways have an op­ti­mal donor. The con­di­tion, which oc­curs in rough­ly 1 per 200,000 births, makes pa­tients so sus­cep­ti­ble to in­fec­tions that they typ­i­cal­ly do not live past in­fan­cy, with­out treat­ment.

On Wednes­day, re­searchers pub­lished a re­port in the The New Eng­land Jour­nal of Med­i­cine de­tail­ing the safe, cu­ra­tive po­ten­tial of their ther­a­py in a clin­i­cal tri­al with pa­tients un­der the age of two. It in­volves ex­tract­ing stem cells from the pa­tient, us­ing a mod­i­fied ver­sion of the HIV virus to in­sert the miss­ing IL2RG gene and in­fus­ing the calls back in­to the sub­ject to re­fur­bish the im­mune sys­tem. Be­fore the cells were in­fused, the pa­tients were giv­en a low dose of chemother­a­py to prime the bone mar­row for the pro­duc­tion of fresh blood cells from the ge­net­i­cal­ly cor­rect­ed stem cells.

Har­ry Malech

A sim­i­lar ap­proach a few decades ago trig­gered leukemia in some pa­tients — which sci­en­tists sus­pect was be­cause the vec­tor un­in­ten­tion­al­ly ac­ti­vat­ed genes that con­trol cell growth. There­fore, the vec­tor used in the study re­port­ed on Wednes­day was en­gi­neered to dodge that out­come, re­searchers said. While oth­er old­er gene ther­a­py ap­proach­es re­stored T cell func­tion, they did not ful­ly re­vive the func­tion of oth­er key im­mune cells, in­clud­ing B cells and nat­ur­al killer (NK) cells, they added.

Nor­mal lev­els of im­mune cells — in­clud­ing T cells, B cells and  NK cells — emerged with­in three to four months af­ter ther­a­py in sev­en of the eight in­fants in the tri­al. The eighth pa­tient ini­tial­ly had low T cell num­bers, but the num­bers climbed fol­low­ing a sec­ond in­fu­sion of the ge­net­i­cal­ly mod­i­fied stem cells.

Vi­ral and bac­te­r­i­al in­fec­tions that par­tic­i­pants had pri­or to treat­ment re­solved af­ter­wards, and four in­fants were al­so able to dis­con­tin­ue treat­ment with in­tra­venous im­munoglob­u­lins — an­ti­body in­fu­sions used to en­hance im­mu­ni­ty.

“The broad scope of im­mune func­tion that our gene ther­a­py ap­proach has re­stored to in­fants with X-SCID — as well as to old­er chil­dren and young adults in our study at NIH — is un­prece­dent­ed,” said Har­ry Malech, chief of the ge­net­ic im­munother­a­py sec­tion in Na­tion­al In­sti­tute of Al­ler­gy and In­fec­tious Dis­eases (NI­AID’s) lab­o­ra­to­ry of clin­i­cal im­munol­o­gy and mi­cro­bi­ol­o­gy.

Malech co-led the de­vel­op­ment of the lentivi­ral gene ther­a­py ap­proach with St. Jude’s Bri­an Sor­renti­no, who died in late 2018. In the tri­al, a to­tal of 10 in­fants have re­ceived the ther­a­py, al­though the pub­lished da­ta re­flects re­sults from eight in­fants who were fol­lowed for a me­di­an of 16.4 months.

New York-based biotech Mus­tang Bio ac­quired the gene ther­a­py for a song last sum­mer, pay­ing St. Jude $1 mil­lion up­front for rights to the pro­gram and of­fer­ing up to $13.5 mil­lion in mile­stone pay­ments. Its mar­ket cap to­day just swelled more than $100 mil­lion, and its shares $MBIO sky­rock­et­ed near­ly 146% to $6.55 in Thurs­day morn­ing trad­ing. The da­ta pre­sent­ed on Wednes­day fol­low pos­i­tive re­sults from the tri­al post­ed by Mus­tang last Au­gust.

A gene ther­a­py de­vel­oped by GSK $GSK for a dif­fer­ent form of SCID (adeno­sine deam­i­nase (ADA) de­fi­cien­cy SCID) was ap­proved in Eu­rope in 2016, but the British drug­mak­er strug­gled to find cus­tomers (rough­ly 15 cas­es are di­ag­nosed in Eu­rope each year) for the pricey treat­ment, de­spite of­fer­ing a mon­ey-back guar­an­tee. Lim­it­ed ac­cess was the big hur­dle, as pa­tients could on­ly be treat­ed in a sin­gle cen­ter in Mi­lan. Even­tu­al­ly, GSK palmed off the gene ther­a­py to UK’s Or­chard Ther­a­peu­tics.

The name “bub­ble boy dis­ease” comes from a fa­mous case in the 1970s, in which a boy in Texas lit­er­al­ly lived in a pro­tec­tive plas­tic bub­ble to cre­ate a germ-free ster­ile en­vi­ron­ment. The case al­so en­tered the cul­tur­al zeit­geist with an episode of the pop­u­lar sit­com Se­in­feld, in which pro­tag­o­nist George Costan­za is taunt­ed by a boy called Don­ald who is af­flict­ed with the con­di­tion (and is en­veloped by a bub­ble) dur­ing a game of Triv­ial Pur­suit. Things get heat­ed, and when Don­ald en­deav­ors to stran­gle a vis­i­bly hot and both­ered George, George’s girl­friend in­ad­ver­tent­ly punc­tures the bub­ble, re­sult­ing in a de­cid­ed­ly macabre end to the scene.

Novotech CRO Ex­pands Chi­na Team as Biotech De­mand for Clin­i­cal Tri­als In­creas­es up to 79%

An increase in demand of up to 79% for clinical trials in China has prompted Novotech the Asia-Pacific CRO to rapidly expand the China team, appointing expert local clinical executives to their Shanghai and Hong Kong offices. The company is planning to expand their team by 30% over the next quarter.

Novotech China has seen considerable demand recently which is borne out by research from GlobalData:
A global migration of clinical research is occurring from high-income countries to low and middle-income countries with emerging economies. Over the period 2017 to 2018, for example, the number of clinical trial sites opened by biotech companies in Asia-Pacific increased by 35% compared to 8% in the rest of the world, with growth as high as 79% in China.
Novotech CEO Dr John Moller said China offers the largest population in the world, rapid economic growth, and an increasing willingness by government to invest in research and development.
Novotech’s 23 years of experience working in the region means we are the ideal CRO partner for USA biotechs wanting to tap the research expertise and opportunities that China offers.
There are over 22,000 active investigators in Greater China, with about 5,000 investigators with experience on at least 3 studies (source GlobalData).

Daniel O'Day [via AP Images]

UP­DAT­ED: Gilead un­leash­es a $5B late-stage cash al­liance with Gala­pa­gos — lay­ing out O'­Day's R&D strat­e­gy

Daniel O’Day is executing his first major development deal since taking over as CEO of Gilead $GILD. And he’s going in deep to ally himself with a longstanding partner.

O’Day announced today that he is spending $5 billion in cash to add new late-stage drugs to Gilead’s pipeline, picking up rights to Galapagos’ $GLPG Phase III IPF drug GLPG1690 alongside adoption of the biotech’s Phase IIb drug GLPG1972 for osteoarthritis. And Gilead is also putting billions more on the table for milestones, gaining options for everything else in Galapagos’ pipeline, with a shot at all rights outside of Europe.

Altogether, Gilead is gaining rights to 6 clinical-stage assets, 20 preclinical programs and everything else being hatched in translation.

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Hal Barron [File photo]

Hal Bar­ron's team at GSK scores a win with pos­i­tive Ze­ju­la PhI­II front­line study — now comes the hard part

Score one for Hal Barron and the new R&D team steering GlaxoSmithKline’s pipeline.

The pharma giant reported this morning that its recently acquired PARP, Zejula (niraparib), hit the primary endpoint on progression-free survival in a frontline maintenance setting for women suffering ovarian cancer — following chemo and regardless of their BRCA status.

GSK bet $5 billion on the Tesaro buyout primarily to get this drug, drawing the shaking heads of biopharma. Why pay a big premium for a drug like this when AstraZeneca was going from strength to strength with Lynparza, ran the argument, having won a hugely important accelerated approval to jump out ahead — way ahead — of the rest of the PARP players? Lynparza — now co-owned by a powerhouse cancer team at Merck — won the first approval in frontline maintenance in ovarian cancer.

Alk­er­mes adds bipo­lar I dis­or­der to its FDA wish­list; Con­go con­firms first Ebo­la case in large city

→ An ever-ambitious Alkermes $ALKS team plans to add bipolar I disorder to its list of conditions for ALKS-3831, which it plans to pitch to the FDA in Q4. Alkermes says they were persuaded to add bipolar I disorder after a pre-NDA meeting with the agency, which came about 7 months after the biotech reported positive data for schizophrenia. The drug is a combo using olanzapine/samidorphan, which they hope will be shown to be as effective as olanzapine without the substantial increase in the risk of weight gain.

Pe­ter Kolchin­sky and Raj Shah raise a $300M fund de­vot­ed to biotech star­tups

Peter Kolchinsky and Raj Shah have another $300 million-plus to play with on the biotech venture side of their investment business. 

The two announced Monday morning that they’ve put together their first pure-play venture fund at RA Capital Management, which has been known to bet on just about every angle in healthcare investing — from rounds to follow-on investments at public companies. This new fund of theirs arrives well into a go-go era of new startup financing, with a particular focus on building new biotechs.

Boehringer buys Swiss biotech in its lat­est M&A deal, go­ing the next-gen can­cer vac­cine route

Boehringer Ingelheim has snapped up a Swiss biotech startup and added their group as a new platform for the oncology pipeline. 

The German biopharma company has bagged Geneva-based AMAL Therapeutics, paying out an unspecified upfront in a $358 million deal — cash, milestones and everything else, all in. Plus there’s 100 million euros on the line for commercial milestones.

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Ab­b­Vie beefs up the on­col­o­gy pipeline, bag­ging an up­start STING play­er with its own unique ap­proach

AbbVie isn’t letting its $63 billion buyout of Allergan stop its M&A/deals team from continuing their work.

Monday morning we learned that the pharma giant is snapping up tiny Mavupharma out of Seattle, a Frazier-backed startup that has its own unique take on STING — which is on the threshold of their first clinical trial.

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Billing it­self as the first AI biotech to launch hu­man tri­als, Re­cur­sion adds $121M C round

Billing itself as the first AI biotech with programs in the clinic, Salt Lake City-based Recursion now has a $121 million bankroll to start gathering human data to see if it’s on the right track. 

“We’re trying to build this discovery engine,” Recursion CEO Chris Gibson tells me ahead of the C round news. “We now have the first two programs in the clinic.” And that, he adds, qualifies as a first for any AI establishment “that actually have something in the clinic.”

FDA bats back As­traZeneca's SGLT di­a­betes drug for Type 1 di­a­betes — block­ing a class on safe­ty fears

The FDA has just fired its latest salvo at the SGLT class of diabetes drugs, blowing up some commercial opportunity at AstraZeneca as part of the collateral damage.

The pharma giant reported early Monday that the FDA has rejected its blockbuster drug Farxiga for Type 1 diabetes that can’t be controlled by insulin. And while the pharma giant maintained its usual grim silence in the face of a setback, this one should be easy to interpret.