Ex­elix­is pulls a sur­prise win in thy­roid can­cer just days ahead of fi­nal Cabome­tyx read­out

Ex­elix­is added a thy­roid can­cer in­di­ca­tion to its su­per-sell­er Cabome­tyx’s la­bel on Fri­day — months be­fore the FDA was ex­pect­ed to make a de­ci­sion, and days be­fore the com­pa­ny was set to un­veil the fi­nal da­ta at #ES­MO21.

At a me­di­an fol­low-up of 10.1 months, dif­fer­en­ti­at­ed thy­roid can­cer pa­tients treat­ed with Cabome­tyx (cabozan­ti­nib) lived a me­di­an of 11 months with­out their dis­ease wors­en­ing, com­pared to just 1.9 months for pa­tients giv­en a place­bo, Ex­elix­is said on Mon­day.

Michael Mor­ris­sey

The piv­otal tri­al, dubbed COS­MIC-311, en­rolled 258 pa­tients from a small but des­per­ate pa­tient pop­u­la­tion: those whose dis­ease pro­gressed fol­low­ing treat­ment with vas­cu­lar en­dothe­lial growth fac­tor re­cep­tor (VEG­FR)-tar­get­ed ther­a­py, and who are re­frac­to­ry to or in­el­i­gi­ble for ra­dioac­tive io­dine.

On­ly about 5% to 15% of thy­roid can­cer pa­tients are re­sis­tant to ra­dioio­dine treat­ment, but with a lack of avail­able treat­ments, they are on­ly ex­pect­ed to live three to five years af­ter di­ag­no­sis.

“Be­fore to­day, pa­tients with ra­dioac­tive io­dine-re­frac­to­ry dif­fer­en­ti­at­ed thy­roid can­cer who have pro­gressed fol­low­ing pri­or VEG­FR-tar­get­ed ther­a­py were fac­ing ag­gres­sive dis­ease and no stan­dard treat­ment op­tion,” prin­ci­pal in­ves­ti­ga­tor Mar­cia Brose said in a state­ment.

The fi­nal COS­MIC-311 analy­sis comes three months af­ter Ex­elix­is un­corked the in­ter­im da­ta, which sug­gest­ed Cabome­tyx re­duced pa­tients’ risk of dis­ease pro­gres­sion or death by 78% com­pared to place­bo af­ter about six months. But de­spite hit­ting the mark on pro­gres­sion-free sur­vival, the drug failed a co-pri­ma­ry end­point of ob­jec­tive re­sponse rate in the first 100 ran­dom­ized pa­tients at 6 months, com­ing in at just 15%. Across the whole in­tent-to-treat pop­u­la­tion, that fig­ure is low­er at just 11%, Ex­elix­is an­nounced on Mon­day.

Ex­elix­is didn’t say much about that end­point in its news re­lease, and CEO Michael Mor­ris­sey was not avail­able for an in­ter­view be­fore press time.

The com­pa­ny’s stock $EX­EL was down about 5% on Mon­day, pric­ing in at $19.67 apiece.

Cabome­tyx was first ap­proved for sec­ond-line kid­ney can­cer in 2016, two years af­ter a prostate can­cer fail­ure forced Ex­elix­is to lay off 70% of its staff. The com­pa­ny’s re­cent strat­e­gy has been push­ing com­bi­na­tion treat­ments and reg­u­la­to­ry fil­ings to ex­pand its list of ap­proved in­di­ca­tions. Last year, Cabome­tyx raked in $718.7 mil­lion in the US.

Reg­u­la­tors grant­ed the drug break­through ther­a­py des­ig­na­tion back in Feb­ru­ary, and as­signed a PDU­FA date of Dec. 4. But the agency un­ex­pect­ed­ly came for­ward with an OK a whole three months ear­ly. The la­bel in­cludes pa­tients 12 years and old­er.

Among the most com­mon Grade 3 or 4 side ef­fects seen in COS­MIC-311 was pal­mar-plan­tar ery­throdyses­the­sia, a con­di­tion that caus­es red­ness, swelling and pain in the hands and feet. Oth­er side ef­fects in­clud­ed hy­per­ten­sion, fa­tigue, di­ar­rhea, and hypocal­cemia. No treat­ment-re­lat­ed deaths were re­port­ed.

“We would like to thank the clin­i­cal tri­al par­tic­i­pants, the physi­cians and their staff who par­tic­i­pat­ed in the COS­MIC-311 tri­al and to ac­knowl­edge the team at the FDA for their col­lab­o­ra­tion dur­ing the quick re­view of our ap­pli­ca­tion,” Mor­ris­sey said in a state­ment.

In 2016, Ipsen struck a deal with Ex­elix­is for ex­clu­sive de­vel­op­ment and com­mer­cial­iza­tion rights to Cabome­tyx out­side of the US and Japan. Take­da has the rights in Japan, which it snapped up in 2017.

This ar­ti­cle has been up­dat­ed to clar­i­fy points made about the de­sign of the study.

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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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.

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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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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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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Bris­tol My­ers pledges to sell its Ac­celeron shares as ac­tivist in­vestors cir­cle Mer­ck­'s $11.5B buy­out — re­port

Just as Avoro Capital’s campaign to derail Merck’s proposed $11.5 billion buyout of Acceleron gains steam, Bristol Myers Squibb is leaning in with some hefty counterweight.

The pharma giant is planning to tender its Acceleron shares, Bloomberg reported, which add up to a sizable 11.5% stake. Based on the offer price, the sale would net Bristol Myers around $1.3 billion.

To complete its deal, Merck needs a majority of shareholders to agree to sell their shares.