CEO Andy Crockett (KalVista)

UP­DAT­ED: KalVista sees a win in PhII for the rare ge­net­ic dis­or­der HAE as it con­tin­ues to chart a post-Mer­ck course

Rough­ly a year af­ter Mer­ck walked away from a part­ner­ship with KalVista fol­low­ing a flop in di­a­bet­ic mac­u­lar ede­ma, the biotech is back with da­ta from an­oth­er pro­gram it hopes can put it back on the map.

KalVista re­port­ed topline Phase II re­sults for its lead can­di­date KVD900, an oral ther­a­py meant to stem the ef­fects of swelling at­tacks caused by the rare ge­net­ic dis­or­der hered­i­tary an­gioede­ma. In the 53-pa­tient tri­al, the pro­gram hit sta­tis­ti­cal sig­nif­i­cance across all end­points, re­duc­ing the need for in­di­vid­u­als to use fur­ther treat­ment in sub­se­quent at­tacks and al­le­vi­at­ing symp­toms more quick­ly than place­bo.

News of the re­sults sent KalVista $KALV shares soar­ing more than 115% in pre-mar­ket trad­ing.

KVD900 it­self is a plas­ma kallikrein in­hibitor that KalVista hopes can be­come the first wide­ly avail­able pill for HAE. The dis­ease man­i­fests as un­pre­dictable swelling in var­i­ous body parts and can be­come life-threat­en­ing if an at­tack oc­curs in the air­ways.

There are lots of treat­ments out there for HAE, all of which are self-ad­min­is­tered in­jec­tions or IV in­fu­sions. Nor­mal­ly, pa­tients liv­ing with the dis­ease are able to feel an at­tack com­ing on, but not how se­vere the at­tack is or how long it will last. Be­cause the swelling can oc­cur ran­dom­ly, in­di­vid­u­als of­ten car­ry around two dif­fer­ent types of treat­ment to be ex­tra sure they’ll have some­thing to stop the at­tacks.

That can be quite cum­ber­some on a pa­tient’s qual­i­ty of life, how­ev­er, KalVista CEO Andy Crock­ett told End­points News. These treat­ments typ­i­cal­ly re­quire cold stor­age, and it can be dif­fi­cult to find a pri­vate spot for pa­tients to give them­selves the in­jec­tions. And the ad­min­is­tra­tion process it­self is al­ready a bur­den giv­en that they’re rac­ing against the clock to tamp down swelling.

With their oral pill, KalVista is bank­ing on the added con­ve­nience and dis­cre­tion such an op­tion will af­ford pa­tients.

“What we think with oral ther­a­py is we have an op­por­tu­ni­ty to re­al­ly bring a par­a­digm shift, which is to re­move those bar­ri­ers,” Crock­ett said. “It can en­able that type of treat­ment ear­ly when the at­tack be­gins that hasn’t been en­abled so far.”

The Phase II study was ran­dom­ized and dou­ble-blind­ed, and sep­a­rat­ed in­to two parts. In­di­vid­u­als re­ceived a sin­gle, open-la­bel dose in the first part, and then were ran­dom­ized in­to the sec­ond part. The tri­al was de­signed to en­com­pass two swelling at­tacks — pa­tients took ei­ther KVD900 or place­bo with­in an hour af­ter the first at­tack, and then used their nor­mal treat­ment reg­i­men fol­low­ing the sec­ond. KalVista en­rolled pa­tients who’d had three at­tacks in the 90 days lead­ing up to the tri­al.

In the pri­ma­ry, KVD900 sig­nif­i­cant­ly re­duced use of such res­cue treat­ments, with 15% of pa­tients need­ing treat­ment af­ter 12 hours in a sec­ond at­tack com­pared to 30% on place­bo. And in a key sec­ondary end­point, the can­di­date sig­nif­i­cant­ly re­duced time to on­set of symp­tom re­lief on a pa­tient-re­port­ed scale, with a me­di­an time of 1.6 hours against nine hours for place­bo. Both fig­ures hit pris­tine p-val­ues, notch­ing p=0.0010 and p<0.0001, re­spec­tive­ly.

De­spite the rel­a­tive ease of such oral treat­ment, Crock­ett said many pa­tients were con­cerned that pills might be less ef­fi­ca­cious than their typ­i­cal in­jecta­bles. But he said Tues­day’s da­ta should al­le­vi­ate those wor­ries as the re­sults, paired with KVD900’s rapid on­set in the Phase II study, shows it can com­pete with the best of the rest.

“Pa­tients in HAE, they want oral ther­a­py. But the in­jectable ther­a­pies they’ve had for a num­ber of years pro­vide re­al­ly good ef­fi­ca­cy,” Crock­ett said. “They don’t want to have to, if you will, trade ef­fi­ca­cy for the ben­e­fit of oral ther­a­py. That’s the promise we look to de­liv­er on now.”

An­a­lysts were al­so im­pressed by the da­ta, with SVB Leerink’s Joseph Schwartz writ­ing that the re­sults ex­ceed­ed even the most bull­ish ex­pec­ta­tions.

“We be­lieve that re­sults could po­ten­tial­ly strength­en in a Ph.3 tri­al of KVD900, as pa­tients will have more con­fi­dence in an in­ves­ti­ga­tion­al treat­ment mak­ing them less like­ly to reach for their res­cue med­i­cine,” Schwartz wrote to in­vestors.

The next steps will in­volve meet­ing with the FDA to de­ter­mine what a piv­otal tri­al might look like. KalVista isn’t of­fer­ing any time­lines on when that meet­ing or the tri­al will oc­cur, but Crock­ett said fu­ture stud­ies will prob­a­bly look sim­i­lar to this Phase II.

Tues­day’s re­sults come al­most one year to the day af­ter Mer­ck dropped out of a part­ner­ship with KalVista, one that had promised up to $760 mil­lion for a di­a­bet­ic mac­u­lar ede­ma drug. Both dos­es of the can­di­date whiffed on the Phase II pri­ma­ry, send­ing shares stum­bling and Mer­ck pack­ing.

Since then, KalVista has fo­cused pri­mar­i­ly on HAE, with KVD900 at the fore­front. The com­pa­ny is al­so work­ing on a pre­ven­ta­tive treat­ment with their KVD824 pro­gram, which is ex­pect­ed to see an IND sub­mis­sion some­time this quar­ter.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Susan Galbraith, AstraZeneca EVP, Oncology R&D

Can­cer pow­er­house As­traZeneca rolls the dice on a $75M cash bet on a buzzy up­start in the on­col­o­gy field

After establishing itself in the front ranks of cancer drug developers and marketers, AstraZeneca is putting its scientific shoulder — and a significant amount of cash — behind the wheel of a brash new upstart in the biotech world.

The pharma giant trumpeted news this morning that it is handing over $75 million upfront to ally itself with Scorpion Therapeutics, one of those biotechs that was newly birthed by some top scientific, venture and executive talent and bequeathed with a fortune by way of a bankroll to advance an only hazily explained drug platform. And they are still very much in the discovery and preclinical phase.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 128,900+ biopharma pros reading Endpoints daily — and it's free.

Lat­est news on Pfiz­er's $3B+ JAK1 win; Pacts over M&A at #JPM22; 2021 by the num­bers; Bio­gen's Aduhelm reck­on­ing; The sto­ry of sotro­vimab; 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.

For those of you who attended #JPM22 in any shape or form, we hope you had a fruitful time. Regardless of how you spent the past hectic week, may your weekend be just what you need it to be.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 128,900+ biopharma pros reading Endpoints daily — and it's free.

A $3B+ peak sales win? Pfiz­er thinks so, as FDA of­fers a tardy green light to its JAK1 drug abroc­i­tinib

Back in the fall of 2020, newly crowned Pfizer chief Albert Bourla confidently put their JAK1 inhibitor abrocitinib at the top of the list of blockbuster drugs in the late-stage pipeline with a $3 billion-plus peak sales estimate.

Since then it’s been subjected to serious criticism for the safety warnings associated with the class, held back by a cautious FDA and questioned when researchers rolled out a top-line boast that their heavyweight contender had beaten the champ in the field of atopic dermatitis — Dupixent — in a head-to-head study.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 128,900+ biopharma pros reading Endpoints daily — and it's free.

Robert Califf, FDA commissioner nominee (Graeme Sloan/Sipa USA/Sipa via AP Images)

Rob Califf ad­vances as Biden's FDA nom­i­nee, with a close com­mit­tee vote

Rob Califf’s second confirmation process as FDA commissioner is already much more difficult than his near unanimous confirmation under the Obama administration.

The Senate Health Committee on Thursday voted 13-8 in favor of advancing Califf’s nomination to a full Senate vote. Several Democrats voted against Califf, including Sen. Bernie Sanders and Sen. Maggie Hassan. Several other Democrats who aren’t on the committee, like West Virginia’s Joe Manchin and Ed Markey of Massachusetts, also said Thursday that they would not vote for Califf. Markey, Hassan and Manchin all previously expressed reservations about the prospect of Janet Woodcock as an FDA commissioner nominee too.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 128,900+ biopharma pros reading Endpoints daily — and it's free.

Michel Vounatsos, Biogen CEO (World Economic Forum/Ciaran McCrickard)

Bio­gen vows to fight CM­S' draft cov­er­age de­ci­sion for Aduhelm be­fore April fi­nal­iza­tion

Biogen executives made clear in an investor call Thursday they are not preparing to run a new CMS-approved clinical trial for their controversial Alzheimer’s drug anytime soon.

As requested in a draft national coverage decision from CMS earlier this week, Biogen and other anti-amyloid drugs will need to show “a meaningful improvement in health outcomes” for Alzheimer’s patients in a randomized, placebo-controlled trial to get paid for their drugs, rather than just the reduction in amyloid plaques that won Aduhelm its accelerated approval in June.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 128,900+ biopharma pros reading Endpoints daily — and it's free.

CRO own­er pleads guilty to ob­struct­ing FDA in­ves­ti­ga­tion in­to fal­si­fied clin­i­cal tri­al da­ta

The co-owner of a Florida-based clinical research site pleaded guilty to lying to an FDA investigator during a 2017 inspection, revealing that she falsely portrayed part of a GlaxoSmithKline pediatric asthma study as legitimate, when in fact she knew that certain data had been falsified, the Department of Justice said Wednesday.

Three other employees — Yvelice Villaman Bencosme, Lisett Raventos and Maytee Lledo — previously pleaded guilty and were sentenced in connection with falsifying data associated with the trial at the CRO Unlimited Medical Research.

‘Skin­ny la­bels’ on gener­ics can save pa­tients mon­ey, re­search shows, but re­cent court de­ci­sions cloud fu­ture

New research shows how generic drug companies can successfully market a limited number of approved indications for a brand name drug, prior to coming to market for all of the indications. But several recent court decisions have created a layer of uncertainty around these so-called “skinny” labels.

While courts have generally allowed generic manufacturers to use their statutorily permitted skinny-label approvals, last summer, a federal circuit court found that Teva Pharmaceuticals was liable for inducing prescribers and patients to infringe GlaxoSmithKline’s patents through advertising and marketing practices that suggested Teva’s generic, with its skinny label, could be employed for the patented uses.

A patient in Alaska receiving an antibody infusion to prevent Covid hospitalizations in September. All but one of these treatments has been rendered useless by Omicron (Rick Bowmer/AP Images)

How a tiny Swiss lab and two old blood sam­ples cre­at­ed one of the on­ly ef­fec­tive drugs against Omi­cron (and why we have so lit­tle of it)

Exactly a decade before a novel coronavirus broke out in Wuhan, Davide Corti — a newly-minted immunologist with frameless glasses and a quick laugh — walked into a cramped lab on the top floor of an office building two hours outside Zurich. He had only enough money for two technicians and the ceiling was so low in parts that short stature was a job requirement, but Corti believed it’d be enough to test an idea he thought could change medicine.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.