Takeda CEO Christophe Weber (Getty Images)

Take­da an­nounces pos­i­tive new ALK+ lung can­cer da­ta as list of crizo­tinib suc­ces­sors widens

Take­da un­veiled new Phase III front­line da­ta for their ALK in­hibitor at Eu­ro­pean So­ci­ety for Med­ical On­col­o­gy Asia Con­gress, show­ing it could de­ter the spread of lung can­cer for two years or more. But the tri­al com­pared the drug, Alun­brig (briga­tinib), against an ear­ly in­hibitor that is no longer best-in-class and the Japan­ese phar­ma will like­ly face sig­nif­i­cant com­pe­ti­tion if reg­u­la­tors grant an ex­pand­ed la­bel. 

“It’s part of the next gen­er­a­tion of ALK in­hibitors,” San­jay Popat, a tho­racic on­col­o­gist at Roy­al Mars­den Hos­pi­tal and an in­ves­ti­ga­tor on the tri­al, Al­ta-1L, told End­points News. “The up­dat­ed da­ta re­al­ly con­firms that briga­tinib is way su­pe­ri­or to crizo­tinib.”

San­jay Popat

The tri­al com­pared briga­tinib against crizo­tinib in 275 ad­vanced non-small-cell-lung-can­cer pa­tients who test­ed pos­i­tive for the ALK gene, and it pro­duced re­sults that don’t take a bio­sta­tis­ti­cian to un­der­stand.

The re­view com­mit­tee found pa­tients on briga­tinib went a me­di­an 24 months with­out the can­cer spread­ing, hit­ting the pri­ma­ry end­point. For crizo­tinib pa­tients? 11 months. (Take­da in­ves­ti­ga­tors found a slight­ly high­er PFS for briga­tinib and a slight­ly low­er PFS for crizo­tinib). 

In pa­tients whose can­cer had spread to the brain — a no­to­ri­ous­ly-dif­fi­cult place to de­liv­er com­pounds, in­clud­ing crizo­tinib — be­fore the start of the tri­al, the drug im­proved pro­gres­sion-free sur­vival by 76% against the con­trol arm, as as­sessed by in­ves­ti­ga­tors. 

“It’s de­signed to cross the blood-brain bar­ri­er,” Popat said of the drug. Pa­tients with brain metas­tases rep­re­sent­ed about 30% of each arm.

The prob­lem for Take­da is that the ALK-land­scape has changed con­sid­er­ably since the Phase III tri­al be­gan and since they ac­quired the com­pound in the $5.2 bil­lion Ari­ad deal. Even since the FDA grant­ed ac­cel­er­at­ed ap­proval for the drug as a sec­ond-line treat­ment in 2017.

Crizo­tinib, the con­trol in the tri­al, was the first ALK in­hibitor ap­proved and came with much ac­claim. While the drug was in Phase I in the late 2000s, the sto­ries of once-ter­mi­nal pa­tients watch­ing their tu­mors shrink made for TV news fod­der. But Pfiz­er, No­var­tis and Roche have all since un­veiled new in­hibitors that can be more ef­fec­tive than the first drug.

Re­searchers cau­tion against com­par­ing clin­i­cal tri­als too di­rect­ly, but Roche’s Ale­cen­sa al­so showed dra­mat­i­cal­ly im­proved pro­gres­sion free-sur­vival against crizo­tinib in sim­i­lar pa­tient pop­u­la­tions, bol­stered by im­proved re­sults in the cen­tral ner­vous sys­tem metas­tases.

Still, the drugs are not iden­ti­cal and, as with many can­cer drugs, re­sis­tance has be­come a prob­lem, with pa­tients rid­ing one in­hibitor while it works and then go­ing to the next. That makes each new in­hibitor a po­ten­tial life­line.

“The one thing that’s clear is that each of the next-gen in­hibitors have demon­strat­ed true su­pe­ri­or­i­ty,” Popat said. “So choos­ing which one is a de­ci­sion be­tween pa­tients and their on­col­o­gists.”

The DCT-OS: A Tech­nol­o­gy-first Op­er­at­ing Sys­tem - En­abling Clin­i­cal Tri­als

As technology-enabled clinical research becomes the new normal, an integrated decentralized clinical trial operating system can ensure quality, deliver consistency and improve the patient experience.

The increasing availability of COVID-19 vaccines has many of us looking forward to a time when everyday things return to a state of normal. Schools and teachers are returning to classrooms, offices and small businesses are reopening, and there’s a palpable sense of optimism that the often-awkward adjustments we’ve all made personally and professionally in the last year are behind us, never to return. In the world of clinical research, however, some pandemic-necessitated adjustments are proving to be more than emergency stopgap measures to ensure trial continuity — and numerous decentralized clinical trial (DCT) tools and methodologies employed within the last year are likely here to stay as part of biopharma’s new normal.

'Chang­ing the whole game of drug dis­cov­ery': Leg­endary R&D vet Roger Perl­mut­ter leaps back in­to work as a biotech CEO

Roger Perlmutter needs no introduction to anyone remotely involved in biopharma. As the R&D chief first at Amgen and then Merck, he’s built a stellar reputation and a prolific career steering new drugs toward the market for everything from cancer to infectious diseases.

But for years, he’s also held a less known title: science partner at The Column Group, where he’s regularly consulted about the various ideas the VCs had for new startups.

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UP­DAT­ED: Pfiz­er hits the brakes on their piv­otal tri­al for a BC­MA/CD3 bis­pe­cif­ic on safe­ty con­cerns while FDA road­block is hold­ing up Duchenne MD PhI­II

Pfizer’s ambitious plan to take a Phase II study of its BCMA CD3-targeted bispecific antibody elranatamab (PF-06863135) and run it through to an accelerated approval has derailed.

The pharma giant said in a release this morning that they have halted enrollment for their MagnetisMM-3 study after researchers tracked three cases of peripheral neuropathy in the ongoing Phase I. They are now sharing info with the FDA as they explore the red safety flag.

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Stéphane Bancel at the Endpoints #JPM20 breakfast panel in San Francisco, January 2020 (Photo: Jeff Rumans, Endpoints News)

Mod­er­na says Covid-19 vac­cine boost­er in­creased im­mune re­sponse against vari­ants of con­cern

About a month after announcing their variant-specific Covid-19 vaccine boosters showed promising results in mice, Moderna says it now has some human data to back it up.

Volunteers given a booster shot about six to eight months after receiving their second dose saw increased antibody levels against SARS-CoV-2 and two variants of concern: B.1.351, which was first identified in South Africa, and P.1, first identified in Brazil, the company said on Wednesday.

FDA ex­tends re­search agree­ment with MIT-li­censed or­gan-on-chip sys­tems

The FDA on Wednesday extended its four-year agreement with CN Bio, a developer of single- and multi-organ-on-chip systems used for drug discovery, for another three years.

CN Bio said the scope of the research performed by the FDA’s Center for Drug Evaluation and Research has expanded to include the exploration of the company’s lung-on-a-chip system to help with the agency’s evaluation of inhaled drugs, in addition to the agency’s work on its liver model.

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In quest to meet user fee goals, FDA’s per­for­mance con­tin­ues down­ward trend

A recent update to the FDA’s running tally of how it’s meeting its user fee-related performance goals during the pandemic shows an agency that is not out of the woods yet.

The latest numbers reveal that for a second straight quarter in 2021, the FDA has met its user fee goal dates for 93% of original new drug applications, which compares with 94% and 98% for the previous two quarters in 2020, respectively.

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Cynthia Butitta (L) and Joe Jimenez

Is that an­oth­er IPO in the mak­ing? Ex-No­var­tis CEO Joe Jimenez and a lead Kite play­er take up new posts at an off-the-shelf ri­val to 2 pi­o­neer­ing drugs

Right on the heels of taking on a $160 million crossover round in a likely leap to Nasdaq, Century Therapeutics CEO Lalo Flores is now pushing ahead with the high-profile ex-Novartis chief Joe Jimenez as chairman.

Jimenez’s greatest fame at Novartis was earned for one of its weakest products, as their pioneering personalized CAR-T Kymriah won the honors for the first such drug to make it to the market. Now a host of players, including Century, are barreling in behind the frontrunners with allogeneic rivals that can be created for off-the-shelf use.

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Joe Wiley, Amryt CEO

A biotech with a yen for pricey rare dis­ease drugs — and bar­gain base­ment shop­ping — adopts an­oth­er or­phan in lat­est M&A pact

After making it through a long, painful haul to get past a CRL and on to an FDA approval last summer, little Chiasma has found a buyer.

Amryt $AMYT, a company known for its appetite for acquiring expensive drugs for rare diseases at bargain prices, snagged Chiasma and its acromegaly drug Mycapssa (octreotide) capsules in an all-stock deal — with an exchange of 0.396 shares of Amryt for every share of Chiasma.

Ngozi Okonjo-Iweala, Director general of WTO (AP Photo/Keystone/Alessandro Della Bella)

Opin­ion: Waiv­ing Covid-19 vac­cine IP could save lives, but where is the man­u­fac­tur­ing ca­pac­i­ty?

Droves of House Democrats in Washington and members of the European Parliament have now glommed onto a major push by India and South Africa at the WTO to abolish all IP around Covid-19 vaccines.

At first blush, waiving this IP sounds like an easy win: More Covid-19 vaccines made locally for more people means more lives saved. Simple enough, especially as low-income countries have received just a tiny fraction of the world’s vaccine allotment so far.