Adrian Rawcliffe, Adaptimmune CEO

Adap­ti­m­mune says it's (near­ly) ready to head to the FDA with TCR can­cer ther­a­py

Six months af­ter an ini­tial re­veal at AS­CO, Adap­ti­m­mune is back in the lime­light with new da­ta Thurs­day. And the com­pa­ny be­lieves it now has enough to go to reg­u­la­tors for what would be the first-ever TCR ther­a­py.

The biotech’s afa­mi-cel pro­gram put out up­dat­ed fig­ures Thurs­day morn­ing with re­searchers not­ing as of Sept. 1, 16 of 47 pa­tients saw their tu­mors shrink while on the ex­per­i­men­tal treat­ment. It’s good enough for a 34% over­all re­sponse rate and, while low­er than the May up­date of 39%, makes Adap­ti­m­mune con­fi­dent enough to say the study will reach its pri­ma­ry end­point.

Though the fi­nal da­ta cut is ex­pect­ed by the end of the year, “it is math­e­mat­i­cal­ly im­pos­si­ble not to meet the pri­ma­ry end­point,” CEO Adri­an Raw­cliffe told End­points News. Fol­low­ing dis­cus­sions with the FDA, the biotech had set an 18% re­sponse rate as an ac­cept­able thresh­old to meet the pri­ma­ry.

“If you as­sume all fu­ture pa­tients will not re­spond,” he added, “the ones that have yet to be as­sessed, the tri­al will still meet the pri­ma­ry end­point.”

De­spite Raw­cliffe’s rosy pic­ture, in­vestors didn’t ap­pear too con­vinced as Adap­ti­m­mune shares $ADAP closed down about 9% in Thurs­day trad­ing.

As the tri­al ap­proach­es its end, Raw­cliffe not­ed that the way in which re­spons­es are clas­si­fied may have changed for some pa­tients as in­de­pen­dent in­ves­ti­ga­tors chimed in, lead­ing to the low­er nu­mer­i­cal fig­ure. Raw­cliffe said it’s the main rea­son two pa­tients who were pre­vi­ous­ly said to have achieved com­plete re­spons­es are no longer la­beled as such.

Nev­er­the­less, the biotech is pre­pared to sub­mit its BLA next year once the fi­nal da­ta are ready. Raw­cliffe de­scribed Adap­ti­m­mune is “very com­fort­able” with the whole da­ta pack­age as it stands and high­light­ed the study’s dura­bil­i­ty mea­sures. Even though 75% of re­spon­ders are still re­ceiv­ing treat­ment, the tri­al has not reached me­di­an du­ra­tion of re­sponse.

Pa­tients’ re­sponse times stretch from about four weeks to more than 65 weeks.

Adap­ti­m­mune had en­rolled pa­tients with two types of sar­co­mas: ad­vanced syn­ovial sar­co­ma or myx­oid/round cell li­posar­co­ma. By each can­cer, the ORR was 36% in syn­ovial sar­co­ma pa­tients and 25% for those with MR­CLS. Pa­tients with these can­cers gen­er­al­ly don’t have many treat­ment op­tions af­ter chemo, Raw­cliffe said, and the five-year mor­tal­i­ty rate is around 70-80%.

Now look­ing to­ward its reg­u­la­to­ry fu­ture, Adap­ti­m­mune may like­ly face sim­i­lar ques­tions as oth­er com­pa­nies that have brought forth cell ther­a­pies. TCR is sim­i­lar to CAR-Ts, in that a pa­tient’s cells are re­moved, re-en­gi­neered and re­placed to tar­get can­cer cells, but TCR goes af­ter a dif­fer­ent pro­tein.

TCRs have his­tor­i­cal­ly been met with a lot of skep­ti­cism, both from re­searchers and in­vestors, but this is the sec­ond time this week a biotech is tout­ing new da­ta. Im­mat­ics re­vealed an ear­ly-stage study that saw eight of 16 pa­tients reg­is­ter an ob­jec­tive re­sponse against a range of sol­id tu­mor types on Tues­day.

Raw­cliffe him­self ad­mit­ted the com­pa­ny has al­ready been asked about its CMC process­es. It’s been at the top of the to-do list in the six months since AS­CO, how­ev­er, and the CEO is con­fi­dent every­thing will be in or­der when the FDA comes knock­ing.

“There’s been five cell ther­a­pies ap­proved to date, and they all came with chal­lenges of their own,” Raw­cliffe said. “Very few of those chal­lenges were re­lat­ed to the clin­i­cal da­ta, so any­body who tells you this is easy, or that there is ze­ro risk as­so­ci­at­ed with it, is liv­ing in cloud cuck­oo land.”

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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Ma­gen­ta halts stem cell work and may sell it­self fol­low­ing pa­tient death, clin­i­cal hold

Magenta Therapeutics said it is halting work on its stem cell transplant drug pipeline and may sell itself, a week after the company reported the death of a patient in an early stage trial of its antibody-drug conjugate.

The Cambridge, MA-based company said it will conduct a “review of strategic alternatives,” and that could include an “acquisition, merger, business combination, or other transaction.”

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How to use ex­ter­nal con­trols: FDA spells out think­ing in new draft guid­ance

The use of real-world evidence to inform the FDA’s decision-making continues apace, with the agency releasing new draft guidance yesterday on how sponsors can compare outcomes of trial participants receiving a test treatment with outcomes in a group of people external to the trial.

The practice of externally controlled trials is common, particularly in oncology or other difficult areas where it’s not ethical or feasible to use internal controls.

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The Big Phar­ma axe: Mer­ck cuts chikun­gun­ya vax, Bris­tol My­ers drops Cy­tomX-part­nered pro­gram, and more

As fourth quarter earnings come in, Big Pharmas are disclosing changes to their pipelines during their investor calls, and sometimes more quietly in presentation appendices.

Merck dropped its chikungunya vaccine candidate, which completed a Phase II study. Merck acquired the vaccine through its purchase of Themis Bioscience in 2020. In developing a vaccine for chikungunya, a mosquito-borne virus, Valneva is the frontrunner, as it submitted its vaccine to the FDA at the end of December.

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Goldfinch Bio CEO Tony Johnson (L) and Karuna Therapeutics CEO Bill Meury

Karuna li­cens­es Goldfinch as­sets to com­pete with Boehringer In­gel­heim in neu­ro­science

Karuna Therapeutics is looking to compete with Boehringer Ingelheim on depression and anxiety with a new license to Goldfinch Bio’s assets, starting with $15 million to the shuttered biotech.

Karuna steps into an arena already being tested by Boehringer in multiple Phase II studies — the two are targeting transient receptor potential canonical 4 and 5, or TRPC4/5, which is thought to have a role in neuroscience indications. Goldfinch’s asset went through a Phase II in kidney diseases, but Karuna’s sights are set on mood and anxiety disorders for now.

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Teresa Graham, incoming Roche Pharmaceuticals CEO

In­com­ing Roche CEO builds out his top team, tap­ping Genen­tech vet to lead phar­ma di­vi­sion

Roche announced another leadership shuffle Thursday morning – the head of global product strategy, Teresa Graham, will take over as CEO of Roche Pharmaceuticals in March while the company’s corporate executive committee will make a spot for Levi Garraway, CMO and executive VP of global product development.

Thomas Schinecker will take over the top spot as Roche group CEO in March, leaving his spot as head of diagnostics.

Roche's headquarters in Basel, Switzerland (Kyle LaHucik for Endpoints News)

Roche ditch­es fi­nal PhI­II for can­cer hope­ful, re­ports set­back for key drug in $1.4B buy­out

Over the past few years, Roche has released news about its AKT inhibitor ipatasertib in drips — most of them negative. The drug yielded mixed data in a key prostate cancer trial, Phase III flops in triple-negative breast cancer forced the pharma giant to pull the plug there, and in mid-2022 Roche trimmed two more early-stage indications in prostate cancer after completing the trials.

Now, the last piece of the program is gone.

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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.

Sanofi scraps PhI­II tri­al for Prin­cip­ia drug af­ter re­view­ing com­pe­ti­tion

Months after the FDA placed Phase III trials of Sanofi’s BTK inhibitor on hold, the company is winding down one of the studies.

Sanofi reported in its Q4 earnings that the URSA study “was discontinued after careful evaluation of the emerging competitive treatment landscape in” myasthenia gravis, a rare disease that causes muscle weakness.

The Phase III, placebo-controlled trial was testing tolebrutinib in patients with the moderate-to-severe form of the disease. It started in late 2021, according to records on clinicaltrials.gov, and was originally designed to recruit 154 participants who were receiving the standard of care.

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