Bryan Stuart (Fulcrum)

Aim­ing to brush last year's flop aside, Ful­crum sees shares sky­rock­et on ear­ly look at sick­le cell pro­gram

Ful­crum Ther­a­peu­tics $FULC is look­ing to re­bound af­ter the Phase II flop of an old Glax­o­SmithK­line drug slashed their mar­ket val­ue in half last Au­gust. And if Tues­day’s stock move­ment is any in­di­ca­tion, in­vestors like what they see.

At an in­ter­im analy­sis of a Phase I study, Ful­crum re­port­ed that their pro­gram de­signed to treat in­her­it­ed blood dis­or­ders hit a sta­tis­ti­cal­ly sig­nif­i­cant rate in two key mea­sure­ments, the com­pa­ny an­nounced Tues­day morn­ing. The re­sults sent Ful­crum shares sky­rock­et­ing more than 125%, send­ing the stock price back above what it had been be­fore last year’s whiff.

The pro­gram, known as FTX-6058, is be­ing de­vel­oped for sick­le cell dis­ease and non-sick­le cell he­mo­glo­binopathies, such as be­ta tha­lassemia.

Tues­day’s re­sults come from a ran­dom­ized and dou­ble-blind­ed study look­ing at healthy vol­un­teers over the course of 14 days. Ful­crum ran both sin­gle-as­cend­ing dose and mul­ti­ple-as­cend­ing dose por­tions of the tri­al, with Tues­day’s da­ta com­ing from the lat­ter where in­di­vid­u­als re­ceived ei­ther 2 mg, 6 mg or 10 mg dos­es dai­ly.

Across the co­horts, re­searchers saw dose pro­por­tion­al in­duc­tions in HBG mR­NA and ac­com­pa­ny­ing in­creas­es in F-retic­u­lo­cytes, two mark­ers on which in­vestors keyed in. The 10 mg dose in par­tic­u­lar proved pos­i­tive, Ful­crum not­ed, with FTX-6058 reach­ing mean changes of 4.5-fold and 4.2-fold in each mea­sure, re­spec­tive­ly.

The pro­gram hit the 4.5-fold in­crease for HBG mR­NA mean fold in­duc­tion at the 14-day mark, while notch­ing the 4.2-fold in­crease in F-retic­u­lo­cytes at the 21-to-24-day safe­ty fol­low-up. Both as­sess­ments hit p-val­ues of p<0.0001.

“Pre­clin­i­cal­ly, we demon­strat­ed con­sis­tent 2-3-fold in­duc­tion of HBG mR­NA and HbF pro­tein both in vit­ro and in vi­vo,” CEO Bryan Stu­art said in a state­ment. He con­tin­ued that the clin­i­cal re­sults “demon­strate the first ev­i­dence that FTX-6058 can achieve or ex­ceed these pre­clin­i­cal thresh­olds pre­dict­ed to pro­vide mean­ing­ful clin­i­cal ben­e­fits to in­di­vid­u­als with SCD.”

An­a­lysts were sur­prised but pleased with the in­creas­es, with Stifel’s Dae Gon Ha not­ing any HBG mR­NA in­duc­tion would have been seen as a pos­i­tive. Ha high­light­ed, how­ev­er, the small tri­al pop­u­la­tion, the short du­ra­tion and the fact that par­tic­i­pants did not have sick­le cell dis­ease are “key caveats” to the safe­ty as­pect of Tues­day’s re­sults.

Ful­crum re­port­ed few tri­al dis­con­tin­u­a­tions and on­ly one se­ri­ous side ef­fect at Grade 4, an asymp­to­matic in­crease in cre­a­tine phos­pho­k­i­nase at the 10 mg dose.

“As an epi­ge­net­ic-tar­get­ing drug that like­ly re­quires chron­ic dos­ing in pa­tients, at this time we can­not rule out po­ten­tial safe­ty/tol­er­a­bil­i­ty sig­nals up­on ex­tend­ed pe­ri­od of dos­ing,” Ha wrote to in­vestors. “Thus, while we are en­cour­aged by the safe­ty progress to-date in this 14-day study, we an­tic­i­pate a more com­pre­hen­sive safe­ty overview to emerge from sub­se­quent tri­als.”

Look­ing ahead, Ful­crum plans to launch a Phase Ib study in sick­le cell pa­tients in the fourth quar­ter, which will dose par­tic­i­pants over three months. Both Ha and SVB Leerink’s Joseph Schwartz wrote they’ll be keep­ing an eye on how the longer treat­ment pe­ri­od af­fects the two mea­sure­ments re­port­ed Tues­day, as well as the dura­bil­i­ty of treat­ment ef­fect.

Ful­crum al­so ex­pects to sub­mit an IND in non-SCD he­mo­glo­binopathies by the end of 2021.

Tues­day’s news comes al­most a year to the day af­ter Ful­crum took a nose­dive off a Phase II fail of the old GSK drug losmapi­mod. Re­searchers had been look­ing at whether the p38α/β MAPK in­hibitor could sig­nif­i­cant­ly re­duce a cer­tain gene’s ex­pres­sion in fa­cioscapu­lo­humer­al mus­cu­lar dy­s­tro­phy af­ter 16 weeks.

Janet Woodcock (Greg Nash/Pool via AP Images)

'I re­al­ly don’t look back': Janet Wood­cock on her tran­si­tion away from drugs

Janet Woodcock may have one of the most historically long and drug-intense tenures in FDA history, but her new role is outside of all things pharma and the once-acting FDA commissioner isn’t looking back.

“No I really don’t look back,” Woodcock told Endpoints News via email on Monday morning. “Yes I will be transitioning. Longer discussion on infrastructure needed.”

An NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

'Xeno­trans­plan­ta­tion is com­ing': New NE­JM pa­per gives de­tailed look in­to 2 pig-to-hu­man kid­ney trans­plant cas­es

The thymokidney is a curious organ, if you could call it that. It’s a sort of Frankensteinian creation — a system of pig thymus embedded underneath the outer layer of a pig’s kidney, made for human transplantation.

In the first case of pig-to-human xenotransplantation of a kidney into a brain-dead patient, the thymokidney quietly featured front and center.

In that experiment, which took place in September of last year, NYU researchers led by Robert Montgomery sutured a pig thymokidney onto the leg of a brain-dead 66-year-old woman. That case was widely reported on by a horde of major media outlets, including the New York Times, the BBC, and an in-depth feature by USA Today.

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Vlad Coric, Biohaven CEO

UP­DAT­ED: Fresh off $11.6B sale to Pfiz­er, New Bio­haven hits Phase III set­back just weeks af­ter Vlad Coric chalked up promise

When Pfizer bought up Biohaven’s migraine portfolio in the largest M&A deal of the year earlier this month, Biohaven CEO Vlad Coric promised the rest of the pipeline, which will live on under the umbrella of New Biohaven, still has a lot to offer. But that vision took a dent Monday as the drugmaker revealed it’s once again flopped on troriluzole.

The glutamate regulator failed to meet the primary endpoint on a Phase III study in patients with spinocerebellar ataxia, an inherited disorder that impairs a person’s ability to walk, speak and swallow. SCA can also lead to premature death.

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Bay­er sounds re­treat from a $670 mil­lion CAR-T pact in the wake of a pa­tient death

Two months after Atara Biotherapeutics hit the hold button on its lead CAR-T 2.0 therapy following a patient death, putting the company under the watchful eye of the FDA, its Big Pharma partners at Bayer are bowing out of a $670 million global alliance. And the move is forcing a revamp of Atara’s pipeline plans, even as research execs vow to continue work on the two drugs allied with Bayer 18 months ago, which delivered a $60 million cash upfront.

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Co­pay coupons gone wrong, again: Pfiz­er pays al­most $300K to set­tle com­plaints in four states

Pfizer has agreed to pay $290,000 to settle allegations of questionable copay coupon practices in Arizona, Colorado, Kansas, and Vermont from 2014 to 2018.

While the company has not admitted any wrongdoing as part of the settlement, Pfizer has agreed to issue restitution checks to about 5,000 consumers.

A Pfizer spokesperson said the company has “enhanced its co-pay coupons to alleviate the concerns raised by states and agreed to a $30,000 payment to each.”

Delaware court rules against Gilead and Astel­las in years-long patent case

A judge in Delaware has ruled against Astellas Pharma and Gilead in a long-running patent case over Pfizer-onwed Hospira’s generic version of Lexiscan.

The case kicked off in 2018, after Hospira submitted an Abbreviated New Drug Application (ANDA) for approval to market a generic version of Gilead’s Lexiscan. The drug is used in myocardial perfusion imaging (MPI), a type of nuclear stress test.

Taye Diggs (courtesy Idorsia)

Idor­sia inks an­oth­er celebri­ty en­dors­er deal with ac­tor and dad Taye Dig­gs as Qu­viviq in­som­nia am­bas­sador

Idorsia’s latest Quviviq insomnia campaign details the relatable dad story of a well-known celebrity — actor and Broadway star Taye Diggs.

Diggs stopped sleeping well after the birth of his son, now more than 10 years ago. Switching mom-and-dad nightly shifts to take care of a baby interrupted his sleep patterns and led to insomnia.

“When you’re lucky enough to be living out your dream and doing what you want, but because of something as simple as a lack of sleep, you’re unable to do that, it felt absolutely — it was treacherous,” he says in an interview-style video on the Quviviq website.

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Belén Garijo, Merck KGaA CEO (Kevin Wolf/AP Images for EMD Serono)

Mer­ck KGaA pumps €440M in­to ex­pand­ing and con­struct­ing Irish man­u­fac­tur­ing fa­cil­i­ties

The area of Ireland famous for Blarney Castle and its cliffsides along the Atlantic Ocean is seeing Merck KGaA expand its commitment there.

The German drug manufacturer is expanding its membrane and filtration manufacturing capabilities in Ireland. The company will invest approximately €440 million ($470 million) to increase membrane manufacturing capacity in Carrigtwohill, Ireland, and build a new manufacturing facility at Blarney Business Park, in County Cork, Ireland.

Rep. Katie Porter (D-CA) (Michael Brochstein/Sipa USA/Sipa via AP Images)

House Dems to Sen­ate lead­er­ship: Quick­ly move a rec­on­cil­i­a­tion bill with drug price ne­go­ti­a­tion re­forms

Twenty House Democrats, including Reps. Katie Porter of California and Susan Wild of Pennsylvania, are calling on Senate leaders to move quickly with a reconciliation bill (meaning they only need a simple majority for passage) with prescription drug pricing reforms, and to include adding new authority for Medicare to negotiate drug prices.

They also called on the Senate to specifically follow suit with the House passage of a $35 per month insulin cap (as Senate Majority Leader Chuck Schumer’s deadline for a vote on that provision has come and gone), and to cap Medicare Part D costs at $2,000 per year for seniors.