Five Prime claims a big win in topline da­ta for their come­back gas­tric can­cer drug as shares sky­rock­et

Five Prime Ther­a­peu­tics $FPRX has kept a rel­a­tive­ly low pro­file fol­low­ing a flop in pan­cre­at­ic can­cer in late 2017. But the biotech de­clared vic­to­ry in gas­tric can­cer Tues­day af­ter re­leas­ing topline da­ta from a 155-per­son Phase II study.

The South San Fran­cis­co-based com­pa­ny an­nounced that its ex­per­i­men­tal drug be­mar­ituzum­ab, in com­bi­na­tion with chemother­a­py, met all of its pre-spec­i­fied ef­fi­ca­cy end­points. Five Prime was aim­ing for a new path­way in the fi­brob­last growth fac­tor re­cep­tor 2b, which is over­ex­pressed in about 30% of all HER2 neg­a­tive gas­tric can­cers, the com­pa­ny says.

In­vestors were thrilled with the news, as the com­pa­ny’s stock price near­ly quadru­pled with­in an hour of the an­nounce­ment. Ahead of Wednes­day’s bell, the shares re­main up by about 400%.

He­len Collins

For ef­fi­ca­cy, Five Prime set their sights on p-val­ues for a 2-sided al­pha of less than 0.2, rather than the typ­i­cal 0.05. That plan in­volved the three end­points of pro­gres­sion free sur­vival, which was the pri­ma­ry, over­all sur­vival and over­all re­sponse rate. CMO He­len Collins tells End­points News their sta­tis­ti­cal analy­sis plan fol­lowed this strat­e­gy be­cause the tri­al was a small Phase II tri­al, rather than a large Phase III.

“We had pre-spec­i­fied the sta­tis­ti­cal sig­nif­i­cance at 0.2, which is typ­i­cal­ly what you do for a Phase II tri­al be­cause it’s much small­er than a Phase III,” Collins said. “And our goal of this tri­al was to get a greater un­der­stand­ing of ex­act­ly who ben­e­fits and who doesn’t ben­e­fit, so that’s the main thing. And this is in some oth­er ways much bet­ter than a typ­i­cal Phase II be­cause it’s ran­dom­ized, dou­ble-blind, place­bo-con­trolled and that’s why we’re thrilled to see the ben­e­fit that we’re see­ing.”

For pro­gres­sion-free sur­vival, out­comes im­proved from 7.4 months to 9.5 months, hit­ting a p-val­ue of 0.073, while over­all re­sponse rate im­proved by 13.1%, good for a p-val­ue of 0.106. But in over­all sur­vival, which CEO Tom Civik lat­er said in a call to in­vestors would like­ly be the pri­ma­ry for a po­ten­tial Phase III tri­al, Five Prime saw a me­di­an of 12.9 months in the con­trol arm and did not reach a fig­ure in the treat­ment arm. That hit a p-val­ue of 0.027.

Civik not­ed in that call that over­all sur­vival for the stan­dard of care is gen­er­al­ly 5 to 7 months.

Orig­i­nal­ly, Five Prime set out to con­duct this tri­al as a Phase III in­tend­ing to en­roll about 550 pa­tients back in 2018, Civik told End­points News. But af­ter paus­ing en­roll­ment last No­vem­ber, the com­pa­ny con­vert­ed the study in­to a Phase II this past May in or­der to get a look at the da­ta soon­er.

Though Collins said the pur­pose of this tri­al was “not de­signed to be filed” to the FDA giv­en the high­er p-val­ues, Civik said the com­pa­ny is go­ing to ap­proach reg­u­la­to­ry bod­ies to see how they view the da­ta.

Tom Civik

“We’ve got 155 pa­tients and the tri­al was ex­e­cut­ed just like a Phase III tri­al, so we’ve got quite a bit of sub­groups that we can in­ter­ro­gate,” Civik said. “We’re go­ing to take our time and make sure we ful­ly go through all that da­ta, and then we will start talk­ing to reg­u­la­to­ry au­thor­i­ties across the world about what are the next steps. The study was not de­signed as a Phase II to be la­bel-en­abling, but it would be com­plete­ly ap­pro­pri­ate for us to have those con­ver­sa­tions with the au­thor­i­ties as to what they think of the da­ta and to what the po­ten­tial next steps might be.”

For safe­ty, side ef­fects were com­pa­ra­ble in both arms at all lev­els, with grade 3 events oc­cur­ring more fre­quent­ly in the treat­ment arm 82.9% to 74%. More pa­tients dis­con­tin­ued be­mar­ituzum­ab com­pared to place­bo 34.2% to 5.2%.

Cowen an­a­lyst Boris Peak­er is peg­ging peak sales at around $400 mil­lion an­nu­al­ly in the US, with an ex­pect­ed piv­otal Phase III like­ly to take two years. In the best case sce­nario, that could re­sult in a po­ten­tial ap­proval some­time in 2023, he wrote to in­vestors.

Wed­bush’s Robert Driscoll took a high­ly pos­i­tive view of the re­sults as well, writ­ing to in­vestors:

Giv­en the con­sis­ten­cy of the da­ta with oth­er 1L gas­tric can­cer stud­ies, high qual­i­ty na­ture of this dou­ble-blind, place­bo-con­trolled study, as well as the sig­nif­i­cant un­met need, we see po­ten­tial for ac­cel­er­at­ed ap­proval for be­ma in FGFR2b-over­ex­press­ing gas­tric can­cers.

Part­nered with Chi­na’s Zai Lab, be­mar­ituzum­ab is a tar­get­ed an­ti­body that blocks FGFs from bind­ing and ac­ti­vat­ing FGFR2b, and Five Prime hopes that it will in­hib­it sev­er­al path­ways. Though the tri­al was mea­sured for gas­tric and gas­troe­sophageal junc­tion can­cers, the drug could be ap­plied to oth­er can­cers with the FGFR2b tar­get.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data is messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data is exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

David Lockhart, ReCode Therapeutics CEO

Pfiz­er throws its weight be­hind LNP play­er eye­ing mR­NA treat­ments for CF, PCD

David Lockhart did not see the meteoric rise of messenger RNA and lipid nanoparticles coming.

Thanks to the worldwide fight against Covid-19, mRNA — the genetic code that can be engineered to turn the body into a mini protein factory — and LNPs, those tiny bubbles of fat carrying those instructions, have found their way into hundreds of millions of people. Within the biotech world, pioneers like Alnylam and Intellia have demonstrated just how versatile LNPs can be as a delivery vehicle for anything from siRNA to CRISPR/Cas9.

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No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty

 

I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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Leen Kawas (L) has resigned as CEO of Athira and will be replaced by COO Mark Litton

Ex­clu­sive: Athi­ra CEO Leen Kawas re­signs af­ter in­ves­ti­ga­tion finds she ma­nip­u­lat­ed da­ta

Leen Kawas, CEO and founder of the Alzheimer’s upstart Athira Pharma, has resigned after an internal investigation found she altered images in her doctoral thesis and four other papers that were foundational to establishing the company.

Mark Litton, the company’s COO since June 2019 and a longtime biotech executive, has been named full-time CEO. Kawas, meanwhile, will no longer have ties to the company except for owning a few hundred thousand shares.

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Pascal Soriot, AstraZeneca CEO (via Getty images)

UP­DAT­ED: FDA slaps As­traZeneca's MCL-1 can­cer drug with a hold af­ter safe­ty is­sue — 2 years af­ter Am­gen axed a trou­bled ri­val

There are new questions being posed about a class of cancer drugs in the wake of the second FDA-enforced clinical hold in the field.

Two years after the FDA hit Amgen with a clinical hold on its MCL-1 inhibitor AMG 397 following signs of cardiac toxicity, AstraZeneca says that regulators hit them with a hold on their rival therapy of the same class.

The pharma giant noted on clinicaltrials.gov that its Phase I/II study for the MCL-1 drug AZD5991 “has been put on hold to allow further evaluation of safety related information.”

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Sur­geons suc­cess­ful­ly at­tach pig kid­ney to a hu­man for the first time, us­ing tech from Unit­ed's Re­vivi­cor

In a first, researchers reportedly successfully transplanted a pig kidney into a human without triggering an immediate immune response this week. And the technology came from the biotech United Therapeutics.

Surgeons spent three days attaching the kidney to the patient’s blood vessels, but when all was said and done, the kidney appeared to be functioning normally in early testing, Reuters and the New York Times were among those to report. The kidney came from a genetically altered pig developed through United’s Revivicor unit.

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Sen. Richard Durbin (D-IL, foreground) and Sen. Richard Blumenthal (D-CT) (Patrick Semansky/AP Images)

Sen­a­tors back FDA's plan to re­quire manda­to­ry pre­scriber ed­u­ca­tion for opi­oids

Three Senate Democrats are backing an FDA plan to require mandatory prescriber education for opioids as overdose deaths have risen sharply over the past decade, with almost 97,000 American opioid-related overdose deaths in the past year alone.

While acknowledging a decline in overall opioid analgesic dispensing in recent years, the FDA said it’s reconsidering the need for mandatory prescriber training through a REMS given the current situation with overdoses, and is seeking input on the aspects of the opioid crisis that mandatory training could potentially mitigate.