Or­chard halts dos­ing of EMA-ap­proved Strimvelis af­ter pa­tient de­vel­ops leukemia

Or­chard Ther­a­peu­tics is pulling its EMA-ap­proved gene ther­a­py Strimvelis off the shelves while it in­ves­ti­gates a po­ten­tial link be­tween the drug and a case of lym­phoid T-cell leukemia.

The biotech $OR­TX said it was no­ti­fied of the ad­verse event a few days ago — just months af­ter it slashed 25% of its work­force in an at­tempt to stray away from rare dis­eases like “bub­ble boy syn­drome,” the one Strimvelis is ap­proved for. The pa­tient was treat­ed un­der a com­pas­sion­ate use pro­gram in 2016, and is now be­ing treat­ed for leukemia at a spe­cial­ty cen­ter. Pre­lim­i­nary find­ings sug­gest the di­ag­no­sis could be linked to an in­ser­tion­al event re­lat­ed to the treat­ment, Or­chard an­nounced.

“No ad­di­tion­al pa­tients will be treat­ed with Strimvelis be­fore the in­ves­ti­ga­tion is com­plete,” the com­pa­ny said in an emailed state­ment. When asked how long the probe might take, the biotech re­spond­ed that an in­ves­ti­ga­tion is un­der­way, and that more in­for­ma­tion will be avail­able once it’s com­plete.

“Or­chard has no­ti­fied EMA of this event, and we re­main in col­lab­o­ra­tive and on­go­ing di­a­logue with the agency,” spokesper­son Chris­tine Har­ri­son said.

Strimvelis was ap­proved in 2016 for pa­tients with se­vere com­bined im­mun­od­e­fi­cien­cy due to adeno­sine deam­i­nase de­fi­cien­cy (ADA-SCID). Af­ter at­tempt­ing to sell off its gene ther­a­py unit for months, Glax­o­SmithK­line trad­ed it to Or­chard in 2018 along with oth­er gene ther­a­py pro­grams for a near­ly 20% stake in the com­pa­ny.

The British drug­mak­er — and lat­er, Or­chard — strug­gled to find cus­tomers among the rare ADA-SCID pa­tient pop­u­la­tion. To date, on­ly 16 peo­ple have been treat­ed with the drug since it was ap­proved.

Back in May, the com­pa­ny re­or­ga­nized to fo­cus on more preva­lent ill­ness­es. It cut 25% of em­ploy­ees, halt­ed the con­struc­tion of a Fre­mont man­u­fac­tur­ing fa­cil­i­ty, shut down a Cal­i­for­nia R&D site, and di­vest­ed two pro­grams (an­oth­er ACA-SCID gene ther­a­py can­di­date and a trans­fu­sion-de­pen­dent be­ta-tha­lassemia can­di­date). When an­nounc­ing the shake­up, Or­chard said it would pri­or­i­tize pro­grams for metachro­mat­ic leukody­s­tro­phy (OTL-200), Wiskott-Aldrich syn­drome (OTL-103), Mu­copolysac­cha­ri­do­sis type I (OTL-203) and Mu­copolysac­cha­ri­do­sis type II­IA, al­so known as San­fil­ip­po syn­drome type A (OTL-201).

Or­chard said that leukemia re­sult­ing from in­ser­tion­al onco­ge­n­e­sis is a known risk of gam­maretro­vi­ral vec­tor-based gene ther­a­py, as de­scribed on the Strimvelis warn­ing la­bel.

The EMA’s prod­uct sum­ma­ry reads:

No cas­es of leukaemia or myelodys­pla­sia have been re­port­ed fol­low­ing treat­ment with Strimvelis. How­ev­er,vec­tor in­ser­tions in­to chro­mo­so­mal re­gions pre­vi­ous­ly as­so­ci­at­ed with leukaemia in com­pa­ra­ble tri­als of­gene ther­a­py in Wiskott Aldrich Syn­drome, X-SCID and Chron­ic Gran­u­lo­ma­tous Dis­ease have been­doc­u­ment­ed. Retro­vi­ral in­ser­tion sites (RIS) have been de­tect­ed ad­ja­cent to or with­in CC­ND2 and LMO2and there is a po­ten­tial risk of leukaemic trans­for­ma­tion fol­low­ing treat­ment with Strimvelis. It is­rec­om­mend­ed that pa­tients be mon­i­tored long term with at least an­nu­al vis­its for the first eleven years andthen at 13 and 15 years post treat­ment with Strimvelis, to in­clude a com­plete blood count with dif­fer­en­tial,bio­chem­istry and thy­roid stim­u­lat­ing hor­mone.

Or­chard’s stock has been on a steady de­cline since Jan­u­ary, when shares reached a high of $15.71 apiece. They closed Fri­day at $4.04 per share.

Strimvelis’ fu­ture re­mains un­clear. “The in­ves­ti­ga­tion is on­go­ing and the com­pa­ny will de­ter­mine the fu­ture of Strimvelis fol­low­ing dis­cus­sions with rel­e­vant stake­hold­ers and will pro­vide fur­ther up­dates as ap­pro­pri­ate,” Or­chard an­nounced.

So­cial im­age: Bob­by Gas­par, Or­chard Ther­a­peu­tics CEO

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

Covid-19 vac­cine boost­ers earn big thumbs up, but Mod­er­na draws ire over world sup­ply; What's next for Mer­ck’s Covid pill?; The C-suite view on biotech; 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.

You may remember that at the beginning of this year, Endpoints News set a goal to go broader and deeper. We are still working towards that, and are excited to share that Beth Snyder Bulik will be joining us on Monday to cover all things pharma marketing. You can sign up for her weekly Endpoints MarketingRx newsletter in your reader profile.

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Roche's Tecen­triq cross­es the fin­ish line first in ad­ju­vant lung can­cer, po­ten­tial­ly kick­ing off gold rush

While falling behind the biggest PD-(L)1 drugs in terms of sales, Roche has looked to carve out a space for its Tecentriq with a growing expertise in lung cancer. The drug will now take an early lead in the sought-after adjuvant setting — but competitors are on the way.

The FDA on Friday approved Tecentriq as an adjuvant therapy for patients with Stage II-IIIA non small cell lung cancer with PD-(L)1 scores greater than or equal to 1, making it the first drug of its kind approved in an early setting that covers around 40% of all NSCLC patients.

No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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Amit Etkin, Alto Neuroscience CEO (Alto via Vimeo)

A star Stan­ford pro­fes­sor leaves his lab for a start­up out to re­make psy­chi­a­try

About five years ago, Amit Etkin had a breakthrough.

The Stanford neurologist, a soft-spoken demi-prodigy who became a professor while still a resident, had been obsessed for a decade with how to better define psychiatric disorders. Drugs for depression or bipolar disorder didn’t work for many patients with the conditions, and he suspected the reason was how traditional diagnoses didn’t actually get at the heart of what was going on in a patient’s brain.

Susan Galbraith, Executive VP, Oncology R&D, AstraZeneca

As­traZeneca on­col­o­gy R&D chief Su­san Gal­braith: 'Y­ou're go­ing to need or­thog­o­nal com­bi­na­tion­s'


Earlier in the week we broadcast our 4th annual European Biopharma Summit with a great lineup of top execs. One of the one-on-one conversations I set up was with Susan Galbraith, the oncology research chief at AstraZeneca. In a wide-ranging discussion, Galbraith reviewed the cancer drug pipeline and key trends influencing development work at the pharma giant. You can watch the video, above, or stick with the script below. — JC

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FDA ad­comm votes unan­i­mous­ly in sup­port of a J&J Covid-19 boost­er two months af­ter one-dose shot

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Friday voted 19-0 in favor of authorizing a second shot of J&J’s Covid-19 vaccine to follow at least two months after the initial dose.

Regulators don’t have to follow VRBPAC’s recommendation, but they almost always do. Considering that the CDC’s advisory committee has already been set to review the expanded EUA, VRBPAC’s recommendation is likely to be adopted.

FDA's vac­cine ad­comm unan­i­mous­ly sup­ports Mod­er­na's boost­er in same pop­u­la­tions as Pfiz­er's boost­er

The FDA’s vaccine advisory committee on Thursday voted 19-0 in support of expanding Moderna’s Covid-19 vaccine EUA for booster doses for certain high-risk individuals. FDA is expected to authorize the Moderna booster shortly.

Similarly to the Pfizer booster shot, Moderna’s will likely be authorized for those older than 65, adults at high risk of severe Covid-19, and adults whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications of Covid-19. But unlike the Pfizer adcomm, where FDA had to scramble to get the committee to vote in favor of a booster, this committee was unanimous with the Moderna shot.

Rob Califf (AP Photo/Pablo Martinez Monsivais, File)

Biden like­ly to nom­i­nate Ver­i­ly's Rob Califf to lead the FDA again

Capping a controversially long period for the FDA to go without a permanent leader, President Joe Biden is likely to select Verily’s Rob Califf, a former FDA commissioner under President Obama, as the next FDA commissioner nominee.

A former Duke cardiologist and member of the prestigious National Academy of Medicine, Califf will be a welcome face for an agency grappling with high-profile retirements in CBER and CDER. He’ll also return to a role that he was comfortable in for a short stint at the end of Obama’s presidency. The Washington Post first reported the news.