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

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

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