Andrew Crockett, KalVista CEO

KalVista ends a PhII study ear­ly af­ter pa­tients suf­fer se­vere and life-threat­en­ing side ef­fects

KalVista took a beat­ing Tues­day af­ter an­nounc­ing it would scrap a Phase II tri­al for one of its ex­per­i­men­tal drugs.

The biotech said in an ear­ly morn­ing press re­lease that it is ter­mi­nat­ing the study for KVD824 af­ter mul­ti­ple pa­tients in every treat­ment group saw un­safe, el­e­vat­ed lev­els of cer­tain liv­er en­zymes. By end­ing the tri­al now, KalVista hopes to save some mon­ey and fun­nel it to­ward an­oth­er study for its lead pro­gram, CEO An­drew Crock­ett said in a state­ment.

In­vestors were not pleased with the news, as KalVista shares $KALV took a beat­ing when the mar­ket opened. The biotech’s stock lost more than half its val­ue, falling 52% in ear­ly Tues­day trad­ing.

KVD824 is an “oral plas­ma kallikrein in­hibitor,” KalVista said, de­signed to treat adults with a rare ge­net­ic dis­or­der called hered­i­tary an­gioede­ma that caus­es flu­id to build up out­side blood ves­sels and block pa­tients’ nor­mal blood flow. Re­searchers ran­dom­ized tri­al par­tic­i­pants to one of three dose lev­els — 300 mg, 600 mg or 900 mg — and in­struct­ed them to take the drug twice a day.

Among the 33 pa­tients who took the drug, sev­en re­port­ed Grade 3 (se­vere) or Grade 4 (life-threat­en­ing) side ef­fects of liv­er en­zyme el­e­va­tion. The ad­verse events took place across a wide time­frame rang­ing from two to 12 weeks post-tri­al start, KalVista said. An­oth­er life-threat­en­ing event was seen in a sep­a­rate pa­tient be­fore they start­ed tak­ing KVD824.

Though these safe­ty is­sues would ap­pear to doom KVD824’s de­vel­op­ment prospects, KalVista said in its press re­lease it would need to fin­ish wrap­ping up da­ta col­lec­tion and ex­am­ine the full un­blind­ed datasets be­fore mak­ing a fi­nal de­ter­mi­na­tion. In an an­a­lyst note out late Tues­day morn­ing, Jef­feries’ Mau­ry Ray­croft de­scribed the re­sult as “dis­ap­point­ing” and said his con­ver­sa­tions with ex­ecs re­vealed they are still work­ing to de­ter­mine the re­la­tion­ship be­tween base­line liv­er en­zymes and HAE sever­i­ty.

This is not the first time KVD824 has run in­to road­blocks. Last year, the FDA placed the pro­gram on clin­i­cal hold af­ter re­quest­ing ad­di­tion­al pre­clin­i­cal da­ta and telling the biotech to amend its Phase II study pro­to­col. The hold was lift­ed in Sep­tem­ber 2021, and Crock­ett said at the time that the study changes were “rel­a­tive­ly straight­for­ward.”

But with the drug falling flat in Phase II — with some se­ri­ous safe­ty con­cerns to boot — KalVista could be giv­ing up a chal­lenge in this space to the Dutch biotech Phar­varis. An­a­lysts had keyed in on this race be­tween the two com­pa­nies, ex­pect­ing a pho­to fin­ish at the FDA. SVB Se­cu­ri­ties’ Joseph Schwartz wrote last year that it wasn’t clear which drug would be the first ap­proved.

Phar­varis, how­ev­er, has run in­to its own brick wall at the agency. In Au­gust, reg­u­la­tors slapped a hold on the biotech’s stud­ies af­ter ask­ing for more pre­clin­i­cal da­ta. Where­as KalVista’s drug worked to in­hib­it plas­ma kallikrein, Phar­varis’ pro­gram, known as PHA121, is a bradykinin B2 re­cep­tor an­tag­o­nist.

Thus far, the on­ly ap­proved drug to treat HAE comes from BioCryst, which picked up a green light for Or­ladeyo back in De­cem­ber 2020. The drug record­ed $114.9 mil­lion in sales for the first half of 2022.

Vac­cine doc­u­ments, young lead­ers and mar­ket tur­moil: End­points' 10 biggest sto­ries of 2022

It’s been a volatile year in the world of biopharma. Market declines reset M&A valuations, and may be beginning to tempt bigger buyers back into dealmaking. Russia’s war in Ukraine disrupted drug sales and clinical trials. A new generation of young biotech leaders emerged in the Endpoints 20(+1) Under 40. And as capital runs dry in a tough environment for raising new funds, companies big and small are taking a look at their headcounts and operations for ways to make it through lean times.

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Tom Riga, Spectrum Pharmaceuticals CEO

Spec­trum im­plodes af­ter a harsh pub­lic slap­down and now a CRL from Richard Paz­dur

The FDA has gone out of its way several times to flatten any expectations for Spectrum’s lung cancer drug poziotinib, including slamming the regulatory door in the biotech’s face four years ago when the their executive crew came calling for a breakthrough drug designation and encouragement from the oncology wing of the FDA.

That stinging early rebuke pointed straight down the path to a corrosive in-house agency review of Spectrum’s attempt to land an accelerated approval for the oral EGFR TKI and a public whipping that included a classic takedown by none other than Richard Pazdur, who slammed the company for “poor drug development” that led to confusion over the dose needed for a slice of NSCLC patients harboring HER2 exon 20 insertion mutations.

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Big Phar­ma's Twit­ter ex­o­dus; Mer­ck wa­gers $1.35B on buy­out; $3.5M gene ther­a­py; 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.

As you start planning for #JPM23, we hope you will consider joining Endpoints News for our live and virtual events. For those who are celebrating Thanksgiving, we hope you are enjoying the long weekend with loved ones. And if you’re not — we’ll see you next week!

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Albert Bourla, Pfizer CEO (John Thys/POOL/AFP via Getty Images)

Pfiz­er CEO un­der fire from UK watch­dog over vac­cine com­ments — re­port

Pfizer CEO Albert Bourla told the BBC last December that he had “no doubt in my mind that the benefits, completely, are in favor” of vaccinating 5- to 11-year-olds for Covid-19. Almost a year later, those comments have reportedly landed him in trouble with a UK pharma watchdog.

Children’s advocacy group UsForThem filed a complaint with the UK’s Prescription Medicines Code of Practice Authority (PMCPA) last year accusing Bourla of making “disgracefully misleading” statements during the BBC interview, including one that “Covid in schools is thriving.” At the time, UK regulators had not yet cleared the vaccine for the 5 to 11 age group, though the vaccine did have a positive opinion from the EMA’s human medicines committee.

FDA tells Catal­ent to fix is­sues at two man­u­fac­tur­ing sites on its own

The CDMO Catalent will have to fix issues at two manufacturing plants in the US and Europe that were subject to inspections by the FDA this summer, giving the company room to correct the issues without facing further regulatory action.

The FDA gave Catalent a “voluntary action indicated” response to two inspections at the contract manufacturer’s site in Bloomington, IN, and Brussels, Belgium. Fixing the issues on its own is a preferable outcome to facing an “official action indicated” response, meaning that an official warning would be sent out or a sit-down with the FDA would be required.

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Robert Califf, FDA commissioner (Jose Luis Magana/AP Images)

Fourth ac­cel­er­at­ed ap­proval in Duchenne? Sarep­ta gets pri­or­i­ty re­view for gene ther­a­py amid FDA scruti­ny

Sarepta is once again on the accelerated approval path for a Duchenne drug, picking up a priority review Monday morning.

The FDA granted the accelerated review to SRP-9001, Sarepta announced Monday, which would become the biotech’s fourth Duchenne drug if approved. Much like SRP-9001 will do, each of the previous three therapies went through the accelerated approval pathway. But unlike the others, SRP-9001 is a gene therapy.

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Sanofi's new headquarters, La Maison Sanofi, in Paris (Credit: Luc Boegly)

Sanofi wel­comes 500 staffers to new Paris HQ af­ter €30M ren­o­va­tion

When Paul Hudson took the helm at Sanofi back in 2019, he promised to reinvent the pharma giant — including its Paris headquarters. This week, the company set up shop in new “state-of-the-art” digs.

La Maison Sanofi, as the new HQ is called, is officially open for business, Hudson announced on Monday. The 9,000-square-meter (just under 97,000-square-foot) space accommodates 500 employees across the company’s government and global support functions teams, including finance, HR, legal and corporate affairs — and it was built with environmental sustainability and hybrid work in mind.

Sta­da to place $50M+ in­vest­ment in a new fa­cil­i­ty in Ro­ma­nia

While Romania may conjure up images of vast mountain ranges and tales of medieval kings, one generic manufacturer has broken ground on a new facility there.

German pharma company Stada said Monday that it has placed a €50 million ($51.9 million) investment into a 100,000 square-meter (1.08 million square-foot) site in Turda, Romania, a city in the Southeast of the country. According to a Stada spokesperson in an email to Endpoints News, the company has developed only 281,500 square feet of the site so far.

Rachael Rollins (Charles Krupa/AP Images)

US seeks jail time for co-CEO of New Eng­land com­pound­ing cen­ter af­ter dead­ly 2012 fun­gal out­break

The US attorney for the district of Massachusetts late last week called on the state’s district court to sentence the former co-owner of the now-defunct New England Compounding Center to 18 months of jail time for his role in the center’s quality deviations that led to more than 100 people dead from a fungal meningitis outbreak.

Gregory Conigliaro was convicted of conspiring with more than a dozen others at NECC to deceive the FDA and misrepresent the fact that the center was only dispensing drugs pursuant to patient-specific prescriptions.