Michael Yang, ViaCyte CEO

Af­ter years of fail­ure, Vi­a­Cyte shows off first proof-of-con­cept for di­a­betes stem cell trans­plants

Sev­en years af­ter they first tried it, Vi­a­Cyte fi­nal­ly has da­ta show­ing that their stem cell treat­ment for di­a­betes — a po­ten­tial cure — can work in a pa­tient.

The da­ta are ex­treme­ly lim­it­ed: They come from a sin­gle pa­tient. But they pro­vide, out­side ex­perts say, the first proof-of-con­cept for an ap­proach that com­pa­nies, in­clud­ing Ver­tex, and di­a­betes re­search foun­da­tions are bet­ting could even­tu­al­ly pro­vide a func­tion­al cure for many pa­tients with type 1 di­a­betes and — down the road — the mil­lions more with type 2 di­a­betes.

The lim­it­ed re­sults were par­tic­u­lar­ly note­wor­thy be­cause Vi­a­Cyte’s first at­tempt at trans­plant­i­ng lab-grown, in­sulin-pro­duc­ing in­to pa­tients be­gin­ning in 2014 had been a fail­ure.

“It’s ac­tu­al­ly very im­pres­sive — I was not im­pressed by their first tri­al, but this is a ma­jor im­prove­ment,” Camil­lo Ri­cor­di, di­rec­tor of the Di­a­betes Re­search In­sti­tute at the Uni­ver­si­ty of Mi­a­mi, told End­points News. “It’s a crit­i­cal first step, it shows that they can work.”

At the same time, the re­sults fell short of Vi­a­cyte’s am­bi­tions to cre­ate a func­tion­al cure. De­spite the new cells, the pa­tient still need­ed to take in­sulin to con­trol her dis­ease.

“I would think it’s not hav­ing enough of an ef­fect,” Jeanne Lor­ing, a pro­fes­sor emer­i­tus at Scripps Re­search, told End­points.

Lor­ing, who launched a fore­run­ner of Vi­a­cyte in 1998 and main­tains a mod­icum of stock, said the re­sults were good but un­sur­pris­ing. “With any of these cell re­place­ment ther­a­pies, the wish is to have a com­plete cure,” she added, “but at least un­til they get bet­ter, it is like­ly to just re­duce the need for in­sulin.”

The pro­ce­dure, first con­ceived decades ago, in­volves tak­ing a bank of stem cells, ma­nip­u­lat­ing them to be­come pan­cre­at­ic pre­cur­sor cells and then im­plant­i­ng them in­to a pa­tient. There, they de­vel­op in­to in­sulin-pro­duc­ing be­ta cells, re­plac­ing the ones that are lost in type 1 di­a­betes pa­tients.

The ap­proach was meant as a scal­able al­ter­na­tive to islet cell trans­plant, an op­er­a­tion that has treat­ed thou­sands of pa­tients, many of who were able to go off in­sulin, but whose reach is lim­it­ed by the lim­it­ed num­ber of avail­able donors.

That was eas­i­er said than done, though. When Vi­a­Cyte first put their cells in­to hu­mans in 2014, en­cap­su­lat­ed in a de­vice meant to shield the lab-grown cells from the pa­tient’s im­mune sys­tem, most of the cells didn’t en­graft. The pa­tients saw lit­tle, if any, change to their dis­ease. The de­vice “ob­vi­ous­ly did not work,” Ri­cor­di said.

Reel­ing from the fail­ure and fac­ing new com­pe­ti­tion from a start­up out of Har­vard called Sem­ma, Vi­a­Cyte tried an eas­i­er ap­proach. They im­plant­ed the cells in a porous de­vice that al­lows blood ves­sels to reach through. That means the cells are ex­posed to the im­mune sys­tem and pa­tients have to take im­muno­sup­pres­sants — lim­it­ing the ther­a­py to on­ly the sick­est 10% of di­a­bet­ics — but it al­so al­lows the cells to ful­ly en­graft.

Nine months af­ter un­der­go­ing ther­a­py, the pa­tient in the study, a woman who had di­a­betes for 36 years and was con­sid­ered “brit­tle,” had mul­ti­ple in­di­ca­tors of high lev­els of in­sulin pro­duc­tion. C-Pep­tide, a bio­mark­er of in­sulin, had in­creased from 0.1 nanogram per mililiter, to 0.8.

Her HbA1C, a mea­sure of blood sug­ar con­trol, dropped from 7.4% to 6.6%, putting her al­most be­low di­a­bet­ic lev­els. She went from hav­ing her blood sug­ar in a healthy range 54% of the time to 84% of the time.

“This case is sem­i­nal,” CEO Michael Yang told End­points. “It’s re­al­ly the first time that it’s ever been shown that an im­plant­ed set of cells in a pa­tient can pro­duce glu­cose re­spons­es, in­sulin and im­pact clin­i­cal mea­sures in a mean­ing­ful way.”

Still the da­ta fall well short of what Yang says is the ul­ti­mate goal: a cure, ef­fec­tive­ly an ar­ti­fi­cial pan­creas. It’s just one pa­tient — a re­sult, in part, of the pan­dem­ic shut­ter­ing en­roll­ment in their study — and that pa­tient re­mains on in­sulin. And at best, Yang said, the treat­ment will work for 2 to 5 years.

Yang said they have more pa­tients ready to en­roll soon and, af­ter fin­ish­ing a 10-12 per­son study, will talk to the FDA about launch­ing a piv­otal tri­al. But they are now in a close com­pe­ti­tion with Ver­tex, who spent $900 mil­lion to buy Sem­ma in 2019, and was cleared ear­li­er this year to launch their own tri­al.

Al­though both now re­ly on im­muno­sup­pre­sants, they are each de­vel­op­ing new ap­proach­es to shield the cells from the im­mune sys­tem, which would open the treat­ment to far more pa­tients. Oth­er com­pa­nies, Ri­cor­di not­ed, are al­so de­vel­op­ing safer and more tol­er­a­ble al­ter­na­tives to im­muno­sup­pre­sants that could be used in tan­dem with the stem cell ther­a­pies.

With more re­sources, Ver­tex could beat Vi­a­Cyte to mar­ket — a prod­uct, in part, of their de­ci­sion to start with the failed en­cap­su­la­tion de­vice in 2014. But Yang, who joined the com­pa­ny ear­li­er this year, said he doesn’t have re­grets.

“I’m a front wind­shield kind of guy,” he said. “So the fact that we have this da­ta, I’m look­ing for­ward to see­ing what we can do.”

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

Gri­fols drops $1B on Ger­man hold­ing com­pa­ny in con­tin­ued plas­ma push

One Spanish biotech is beefing up its plasma therapy operations, and on Friday, it announced that it’s doing so in a billion-dollar deal.

Grifols is now the largest shareholder of Biotest, a company valued at more than $1.8 billion. By teaming up, the two will try to increase the number of plasma therapies available and increase patient access around the world, Grifols said in a press release.

The company did so by acquiring holding company Tiancheng Pharmaceutical, the Germany-based owner of nearly 90% of Biotest shares, for nearly $1.27 billion. Grifols now owns nearly 90% of Biotest voting rights and almost 45% of the total share capital of Biotest.

Amgen VP of R&D David Reese

Am­gen rolls out da­ta for KRAS in­hibitor com­bo study in col­orec­tal can­cer, hop­ing to move on from ug­ly ear­ly re­sults

With the first win for its KRAS inhibitor sotorasib in hand, Amgen is pushing ahead with an aggressive clinical plan to capitalize on its first-to-market standing. The drugmaker thinks combinations — in-house or otherwise — could offer a path forward, and one early readout from that strategy is bearing fruit.

A combination of Amgen’s sotorasib and its EGFR inhibitor Vectibix posted an overall response rate of 27% in 26 patients with advanced colorectal cancer (CRC) with the KRAS-G12C mutation, according to data from the larger Phase Ib/II CODEBREAK 101 study set to present at this weekend’s virtual ESMO Congress.

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Eu­ro­pean study finds that Gilead­'s Covid-19 an­tivi­ral remde­sivir shows no clin­i­cal ben­e­fit

Gilead’s remdesivir — or Veklury, as it’s marketed in the US — raked in around $2.8 billion last year as the only FDA-approved antiviral to treat Covid-19. But new data from a European study suggest the drug, which has been given to about half of hospitalized Covid patients in the country, has no actual benefit.

The open-label DisCoVeRy trial enrolled Covid-19 patients across 48 sites in Europe to test a handful of treatments, including remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, and hydroxychloroquine. To participate, patients had to show symptoms for seven days and require oxygen support. A total of 429 patients were randomized to receive remdesivir plus standard of care, while 428 were assigned to standard of care alone.

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Covid-19 roundup: FDA re­veals boost­er ad­comm ques­tion; Eli Lil­ly's an­ti­body cock­tail cleared for pre­ven­tion

The FDA released briefing documents this week from the agency and Pfizer each outlining their arguments for today’s Covid-19 booster shot adcomm, but one thing conspicuously missing was the question on which panel members would be voting. But late Thursday night, regulators published that question.

Adcomm members will be asked whether or not the safety and efficacy data from Pfizer/BioNTech’s original Phase III study “support approval” of a booster shot at least six months after the second dose in individuals older than 16. The question notably excludes the real-world data from Israel and other analyses that Pfizer and the Biden administration had said would be a centerpiece of their arguments for boosters.

A Pfiz­er part­ner wel­comes ex-ADC Ther­a­peu­tics CMO Jay Fein­gold to the team; Amid tough sled­ding, Im­muno­vant choos­es Eli Lil­ly alum as CFO

→ Last week we told you about the CMO revolving door at ADC Therapeutics, as Joseph Camardo replaced the departing Jay Feingold. The next opportunity for Feingold in the CMO slot has opened up at antibody-drug conjugate and mAb developer Pyxis Oncology, which has added several new execs and scientific advisory board members in recent months, including ex-Immunovant CFO Pamela Yanchik Connealy. Before his tenure at ADC, Feingold was Daiichi Sankyo’s VP of US medical affairs and chairman of the Global Medical Affairs Oversight Committee. Within weeks in March, Pyxis struck a licensing deal with Pfizer for two of its ADCs and raked in $152 million from a Series B round.

Ali Tehrani, Zymeworks CEO

Zymeworks squares up with Her­ceptin af­ter HER2 bis­pe­cif­ic aces mid-stage test in esophageal can­cer

Roche’s Herceptin has long stood as standard of care across multiple advanced cancers, but a suite of next-gen players are looking to beat the aging giant at its own game. In HER2-expressing esophageal cancer, BeiGene partner Zymeworks thinks its bispecific antibody could have the juice to get it done.

Zymeworks’ bispecific antibody zanidatamab, combined with one of two chemotherapy regimens, posted an overall response rate of 75% in patients with advanced gastroesophageal adenocarcinoma (GEA) who had not previously received a HER2-targeted cancer therapy, the Vancouver-based biotech said Thursday.

UP­DAT­ED: Gilead keeps push­ing trove of Trodelvy da­ta as it seeks to be­come new stan­dard of care in TNBC

Gilead is continuing to churn out results for its newly approved drug Trodelvy, and #ESMO21 is the latest stop on the data train.

The biopharma put out new quality of life data in second-line patients with metastatic triple-negative breast cancer, saying that a sub-analysis from their Phase III study showed significant and clinically meaningful improvements in health-related quality of life over standard of care.