#AACR17 roundup: Bris­tol-My­ers, Mer­ck KGaA and Pfiz­er in the spot­light, mark­ing progress with check­points

PHO­TO: © AACR/Todd Buchanan 2017

Julie Brah­mer, Johns Hop­kins
Bris­tol-My­ers IDs a sub­set of pa­tients who see a durable, 5-year re­sponse to Op­di­vo

Wash­ing­ton, DC — Now that the first wave of PD-1 check­point in­hibitors have been in use for awhile, we’re start­ing to see just how durable they can be for some pa­tients. In an up­date on Op­di­vo at AACR, Bris­tol-My­ers Squibb re­ports that they tracked a 5-year sur­vival rate of 16% for pa­tients with ad­vanced cas­es of non-small cell lung can­cer.

Based on his­tor­i­cal da­ta, Bris­tol-My­ers says that pa­tients in that cat­e­go­ry once could on­ly ex­pect a sur­vival rate of less than 5%.

“This is the first re­port of the long-term sur­vival rate in pa­tients with metasta­t­ic NSCLC treat­ed with an im­mune check­point in­hibitor. Our study re­sults show that for a small sub­set of pa­tients, im­munother­a­py can work for a very long time,” said Julie Brah­mer, as­so­ciate pro­fes­sor of on­col­o­gy at the Bloomberg~Kim­mel In­sti­tute for Can­cer Im­munother­a­py at Johns Hop­kins.

Fouad Namouni, Bris­tol-My­ers Squibb

What dis­tin­guish­es these pa­tients?

Bris­tol-My­ers Squibb’s Fouad Namouni, who runs the on­col­o­gy de­vel­op­ment group, tells me that they’re still work­ing on that, try­ing to un­der­stand the bio­mark­ers that could flag which pa­tients are most like­ly to get the most durable re­spons­es. One like­ly an­swer, he notes, is that the pa­tients with the most in­flam­ma­to­ry tu­mors, with the largest mu­ta­tion bur­den, could be ben­e­fit­ing dis­pro­por­tion­ate­ly.

More mu­ta­tions, he says, means that the tu­mors be­come “more vis­i­ble to the im­mune cell,” tar­get­ing them for de­struc­tion.

Pfiz­er, Mer­ck KGaA spruce up Baven­cio’s pro­file with a da­ta up­date
Howard Kauf­man, Rut­gers

Mer­ck KGaA and its part­ner Pfiz­er turned up at AACR over the week­end with some im­proved out­comes for their check­point drug avelum­ab, re­cent­ly ap­proved as Baven­cio for rare cas­es of Merkel cell car­ci­no­ma.

Ev­i­dence of a slight­ly amped up and more durable re­sponse will help these new ar­rivals on the check­point scene make quick progress as it works its way in­to an in­creas­ing­ly crowd­ed field. Start­ing with this rare form of skin can­cer, they now have 30 tri­als un­der­way in var­i­ous in­di­ca­tions, com­ing in be­hind Mer­ck, Bris­tol-My­ers and Roche.

As­traZeneca will be the next to ar­rive, as it leaps in­to a block­buster field with dur­val­um­ab. And be­hind As­traZeneca lie a whole new wave of check­points that are be­ing hur­ried along, as the pi­o­neers start a slew of com­bi­na­tion stud­ies — as our lat­est sto­ry on the IDO1 com­bos in­di­cate — to ad­vance their work.

The re­searchers for these two com­pa­nies re­port­ed that:

(A)fter longer fol­low-up, the num­ber of pa­tients to have a re­sponse in­creased to 29, for an over­all re­sponse rate of 33 per­cent af­ter a me­di­an of 16.4 months of fol­low-up. In ad­di­tion, the num­ber of pa­tients to have a com­plete re­sponse in­creased to 10 be­cause one of the par­tial re­spons­es had im­proved to a com­plete re­sponse, and an­oth­er pa­tient new­ly record­ed to have a re­sponse had a com­plete re­sponse.

At the time of da­ta cut­off, 21 of the re­spons­es were on­go­ing and the me­di­an du­ra­tion of re­sponse had not been reached. The re­searchers es­ti­mat­ed that 74 per­cent of pa­tients will have a re­sponse that lasts one year or longer.

Mer­ck KGaA sped through clin­i­cal tri­als in three-and-a-half years to get this first ap­proval, a mile­stone that Pfiz­er helped make hap­pen with a record $850 mil­lion up­front for its part­ner­ship arrange­ment with the Ger­man Mer­ck, which has gone well over a decade with­out a block­buster ad­di­tion from its R&D ops.

Howard Kauf­man, a sur­gi­cal on­col­o­gist at Rut­gers Can­cer In­sti­tute of New Jer­sey, not­ed:

The find­ings of long-term re­spons­es and well-tol­er­at­ed safe­ty pro­file sug­gest that avelum­ab could be an im­por­tant new agent for pa­tients with Merkel cell car­ci­no­ma who have failed pri­or chemother­a­py. Giv­en these re­sults, it will be in­ter­est­ing to de­ter­mine whether re­sponse rates could be in­creased by giv­ing avelum­ab pri­or to chemother­a­py or in com­bi­na­tion with oth­er treat­ments.

Op­di­vo, Yer­voy com­bo scores high­er sur­vival rate for melanoma, with worse ad­verse events

Bris­tol-My­ers, which has been work­ing on bol­ster­ing its case for a com­bi­na­tion of Op­di­vo and Yer­voy in treat­ing can­cer, al­so turned up at AACR with new da­ta that high­lights im­proved sur­vival rates for melanoma rates.

James Larkin, On­col­o­gist

On­col­o­gist James Larkin and col­leagues en­rolled 945 first-line pa­tients with ad­vanced melanoma and ran­dom­ly as­signed them in equal groups to nivolum­ab plus ip­il­i­mum­ab, nivolum­ab, or ip­il­i­mum­ab.

Af­ter a min­i­mum fol­low-up of 28 months, in­ves­ti­ga­tors re­port­ed, me­di­an over­all sur­vival among those pa­tients ran­dom­ly as­signed ip­il­i­mum­ab was 20 months. The me­di­an OS had not been reached for the nivolum­ab plus ip­il­i­mum­ab or the nivolum­ab plus place­bo arms.

A to­tal of 64% in the com­bo arm achieved two-year sur­vival, the high­est rate. The rate was 59% and 45% among those ran­dom­ly as­signed nivolum­ab plus place­bo and ip­il­i­mum­ab alone. But the com­bo arm al­so ex­pe­ri­enced worse ad­verse events.

Re­searchers added:

A sim­i­lar trend was seen for me­di­an du­ra­tion of re­sponse. Me­di­an du­ra­tion of re­sponse had not been reached in the nivolum­ab plus ip­il­i­mum­ab arm, while it was 31.1 months and 18.2 months for the nivolum­ab plus place­bo arm and ip­il­i­mum­ab alone arm, re­spec­tive­ly. In de­scrip­tive analy­ses, mean­ing the study was not pow­ered for this com­par­i­son, pa­tients ran­dom­ly as­signed nivolum­ab plus ip­il­i­mum­ab had a 12 per­cent low­er risk of death com­pared with those ran­dom­ly as­signed nivolum­ab plus place­bo.

“It is ex­cit­ing to see that ini­tial re­sults sug­gest that the nivolum­ab plus ip­il­i­mum­ab com­bi­na­tion pro­vides fa­vor­able sur­vival out­comes com­pared with ip­il­i­mum­ab alone,” said Larkin. “How­ev­er, the com­bi­na­tion al­so re­sults in a high­er rate of se­vere ad­verse events than nivolum­ab or ip­il­i­mum­ab alone, so it is im­por­tant to con­sid­er this when mak­ing treat­ment de­ci­sions for pa­tients.”

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.

UP­DAT­ED: Boehringer nabs FDA's first in­ter­change­abil­i­ty des­ig­na­tion for its Hu­mi­ra com­peti­tor — but will it mat­ter?

The FDA late Friday awarded Boehringer Ingelheim the first interchangeability designation for its Humira biosimilar Cyltezo, meaning that when it launches in July 2023, pharmacists will be able to automatically substitute the Boehringer’s version for AbbVie’s mega-blockbuster without a doctor’s input.

The designation will likely give Boehringer, which first won approval for Cyltezo in 2017, the leg up on a crowded field of Humira competitors.

Bio­gen hit by ALS set­back with PhI­II fail­ure for tofersen — but fol­lows a fa­mil­iar strat­e­gy high­light­ing the pos­i­tive

Patients and analysts waiting to hear Sunday how Biogen’s SOD1-ALS drug tofersen fared in Phase III didn’t have to wait long for the top-line result they were all waiting for. The drug failed the primary endpoint on significantly improving the functional and neurologic decline of patients over 28 weeks as well as the extension period for continued observation.

In fact, there was very little difference in response.

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Reshma Kewalramani, Vertex CEO (YouTube)

Ver­tex gets much-need­ed win with ‘ex­tra­or­di­nary’ first pa­tient re­sults on po­ten­tial di­a­betes cure

Vertex said Monday that the first patient dosed with its cell therapy for type 1 diabetes saw their need for insulin injections vanish almost entirely, a key early step in the decades-long effort to develop a curative treatment for the chronic disease.

The patient, who had suffered five potentially life-threatening hypoglycemic — or low blood sugar — episodes in the year before the therapy, was injected with synthetic insulin-producing cells. After 90 days, the patient’s new cells produced insulin steadily and ramped up their insulin production after a meal like normal cells do, as measured by a standard biomarker for insulin production.

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No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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Susan Galbraith, Executive VP, Oncology R&D, AstraZeneca

As­traZeneca on­col­o­gy R&D chief Su­san Gal­braith: 'Y­ou're go­ing to need or­thog­o­nal com­bi­na­tion­s'


Earlier in the week we broadcast our 4th annual European Biopharma Summit with a great lineup of top execs. One of the one-on-one conversations I set up was with Susan Galbraith, the oncology research chief at AstraZeneca. In a wide-ranging discussion, Galbraith reviewed the cancer drug pipeline and key trends influencing development work at the pharma giant. You can watch the video, above, or stick with the script below. — JC

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Jeffrey Nau, Oyster Point Pharma CEO

FDA OKs an in­haled ver­sion of smok­ing ces­sa­tion drug Chan­tix — for a com­mon eye dis­ease

Oyster Point Pharma now has its first FDA-approved product — Tyrvaya. And the biotech has taken a unique route to get there by using an old drug with a storied past.

The New Jersey biotech announced this morning that the FDA has approved their nasal spray product for dry eye disease on Friday — the first nasal spray to be approved for the disease. The product’s active ingredient is 0.03 mg of varenicline, also known as smoking cessation aid Chantix.

Sheldon Koenig, Esperion CEO

Es­pe­ri­on gets out the bud­get ax, chop­ping 170 staffers as its big drug launch sput­ters

Esperion’s executive team spent years insisting that they had found the sweet spot in the market for their cholesterol drug. But that strategy has soured badly, and after struggling to sell its heart disease pill for more than a year, the biotech says it will cut about 40% of its staff over the next few weeks.

The layoffs will take place across the board, from sales and marketing to R&D, CEO Sheldon Koenig told Endpoints News on Monday. While the chief executive declined to elaborate on how many employees will be affected, an SEC filing stated that approximately 170 staffers are on the chopping block.

Two drug­mak­ers hit with PDU­FA date de­lays from FDA amid back­log of in­spec­tions

As the FDA is weighed down with more and more pandemic responsibilities, the agency is beginning to miss PDUFA dates with more frequency too. Two different companies on Monday said they received notices that the FDA has not completed their drug reviews on time.

The review of an NDA for Avadel Pharmaceuticals’ candidate treatment for narcolepsy is not coming this month, the company said, and the review of UCB’s BLA for bimekizumab, used to treat moderate to severe plaque psoriasis, will miss its target date as well.

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