With deals in tow, Roche ends 2019 with five dis­card­ed pro­grams

With sales com­ing in just shy of Wall Street es­ti­mates and prof­it that just beat ex­pec­ta­tions, Roche capped off 2019 on a high hav­ing fi­nal­ly con­sum­mat­ed its ar­du­ous ac­qui­si­tion of Spark Ther­a­peu­tics. That buy­out was marred with no less than 10 de­lays due to reg­u­la­to­ry con­cerns about an­ti­com­pet­i­tive deal­mak­ing. As is the tra­di­tion, the com­pa­ny al­so culled a num­ber of ex­per­i­men­tal drugs across its pipeline.

Source: Roche, 2020

Click on the im­age to see the full-sized ver­sion

The first ear­ly-stage pro­gram on the chop­ping block is a com­bi­na­tion of its can­cer ther­a­py Ven­clex­ta, which is part­nered with Ab­b­Vie and was first ap­proved in 2016 for CLL. Last year, the com­pa­nies were forced to press pause on a range of mul­ti­ple myelo­ma tri­als test­ing the drug, af­ter high­er death rates on the Ven­clex­ta arm forced the FDA to im­pose a par­tial hold on pa­tient re­cruit­ment. A few months lat­er, one tri­al was al­lowed to re­sume, but Ven­clex­ta re­mains un­der a cloud. On Thurs­day, the Swiss drug­mak­er cut a Phase I study test­ing the drug in com­bi­na­tion with the TKI Cotel­lic and check­point in­hibitor Tecen­triq in pa­tients with re­lapsed or re­frac­to­ry mul­ti­ple myelo­ma.

An­oth­er ear­ly-stage cut is the Chugai-part­nered bis­pe­cif­ic an­ti­body — ERY974 — that was un­der eval­u­a­tion for use in sol­id tu­mors.

In ad­di­tion, a Phase I pro­gram for chron­ic he­pati­tis B in­fec­tion — RG6004 — was al­so dis­card­ed. The de­ci­sion may be re­lat­ed to Roche’s $200 mil­lion up­front deal with Dicer­na, which is work­ing on an RNAi ap­proach in a bid to cure the dis­ease.

Last year, Roche’s Tecen­triq — in com­bi­na­tion with chemother­a­py — man­aged to se­cure ap­proval for pa­tients with metasta­t­ic PD-L1 pos­i­tive triple-neg­a­tive breast can­cer (TNBC), a no­to­ri­ous­ly hard-to-treat form of the dis­ease. An­oth­er TNBC drug in Roche’s ar­se­nal is ipatasert­ib (RG7440), a drug the com­pa­ny got from Ar­ray to ad­dress T cell-me­di­at­ed im­munother­a­py re­sis­tance and is cur­rent­ly in a late-stage monother­a­py study. Last April, Roche post­ed some en­cour­ag­ing ear­ly re­sults from a tri­al test­ing ipatasert­ib+Tecen­triq+pa­cli­tax­el — and have since moved in­to a Phase III TNBC tri­al. How­ev­er, Roche has now killed a pro­gram test­ing the drug’s im­pact in com­bi­na­tion with Tecen­triq and Tax­ane in TNBC.

Speak­ing of Tecen­triq — Roche’s star PD-L1 ther­a­py got a rare ap­proval in 2019 for an in­di­ca­tion that Mer­ck’s lead­ing check­point in­hibitor Keytru­da was not able to make an over­all sur­vival im­pact on — ex­ten­sive-stage small cell lung can­cer. SCLC pa­tients ac­count for rough­ly 10% to 15% of all lung can­cer cas­es. The bulk of di­ag­noses, how­ev­er, come from non-small cell lung can­cer (NSCLC), mak­ing it the most lu­cra­tive mar­ket with­in on­col­o­gy. A sec­tion of this pop­u­la­tion — non-squa­mous NSCLC — was ini­tial­ly with­in the grasp of Keytru­da, but Tecen­triq com­bos have al­so se­cured ap­proval for cer­tain front­line cas­es. On Thurs­day how­ev­er, one Tecen­triq com­bo in­clud­ing two chemother­a­pies was giv­en the boot in a late-stage tri­al test­ing pa­tients with non-squa­mous NSCLC.

And fi­nal­ly, there’s Roche’s ex­per­i­men­tal DMD ther­a­py. Back in No­vem­ber, Roche pub­licly de­clared its de­ci­sion to aban­don the drug —RG6206 — that was de­signed to in­hib­it myo­statin, af­ter it failed a fu­til­i­ty analy­sis. Back in 2017, the drug was li­censed for $170 mil­lion up­front from Bris­tol-My­ers Squibb. The pro­gram marked yet an­oth­er fail­ure in a field lit­tered with flopped myo­statin drugs — in­clud­ing com­pounds from No­var­tis and Pfiz­er.

So­cial im­age: Roche

What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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As­traZeneca touts Imfinzi im­munother­a­py com­bos for lung can­cer in push to dri­ve PD-L1 drug up­take

Facing the big dogs in the PD-(L)1 space, AstraZeneca has taken its own contender Imfinzi into blockbuster territory in its four years on the market but sees even bigger things for the drug. Combinations could be the key, and early results from a mid-stage test are adding some fuel to that strategy.

Imfinzi combined with one of two investigational immunotherapies — a CD73 antibody dubbed oleclumab or an anti-NGK2a named monalizumab — topped Imfinzi alone in terms of overall response and progression-free survival in patients with stage III non-small cell lung cancer whose tumors had not worsened during concurrent chemoradiation, according to interim data from the Phase II COAST trial set to be presented at #ESMO21.

Amgen VP of R&D David Reese

Am­gen rolls out da­ta for KRAS in­hibitor com­bo study in col­orec­tal can­cer, hop­ing to move on from ug­ly ear­ly re­sults

With the first win for its KRAS inhibitor sotorasib in hand, Amgen is pushing ahead with an aggressive clinical plan to capitalize on its first-to-market standing. The drugmaker thinks combinations — in-house or otherwise — could offer a path forward, and one early readout from that strategy is bearing fruit.

A combination of Amgen’s sotorasib and its EGFR inhibitor Vectibix posted an overall response rate of 27% in 26 patients with advanced colorectal cancer (CRC) with the KRAS-G12C mutation, according to data from the larger Phase Ib/II CODEBREAK 101 study set to present at this weekend’s virtual ESMO Congress.

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Gri­fols drops $1B on Ger­man hold­ing com­pa­ny in con­tin­ued plas­ma push

One Spanish biotech is beefing up its plasma therapy operations, and on Friday, it announced that it’s doing so in a billion-dollar deal.

Grifols is now the largest shareholder of Biotest, a company valued at more than $1.8 billion. By teaming up, the two will try to increase the number of plasma therapies available and increase patient access around the world, Grifols said in a press release.

The company did so by acquiring holding company Tiancheng Pharmaceutical, the Germany-based owner of nearly 90% of Biotest shares, for nearly $1.27 billion. Grifols now owns nearly 90% of Biotest voting rights and almost 45% of the total share capital of Biotest.

Dan O'Day, Gilead CEO (Jim Watson/AFP via Getty Images)

Eu­ro­pean study finds that Gilead­'s Covid-19 an­tivi­ral remde­sivir shows no clin­i­cal ben­e­fit

Gilead’s remdesivir — or Veklury, as it’s marketed in the US — raked in around $2.8 billion last year as the only FDA-approved antiviral to treat Covid-19. But new data from a European study suggest the drug, which has been given to about half of hospitalized Covid patients in the country, has no actual benefit.

The open-label DisCoVeRy trial enrolled Covid-19 patients across 48 sites in Europe to test a handful of treatments, including remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, and hydroxychloroquine. To participate, patients had to show symptoms for seven days and require oxygen support. A total of 429 patients were randomized to receive remdesivir plus standard of care, while 428 were assigned to standard of care alone.

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Covid-19 roundup: FDA re­veals boost­er ad­comm ques­tion; Eli Lil­ly's an­ti­body cock­tail cleared for pre­ven­tion

The FDA released briefing documents this week from the agency and Pfizer each outlining their arguments for today’s Covid-19 booster shot adcomm, but one thing conspicuously missing was the question on which panel members would be voting. But late Thursday night, regulators published that question.

Adcomm members will be asked whether or not the safety and efficacy data from Pfizer/BioNTech’s original Phase III study “support approval” of a booster shot at least six months after the second dose in individuals older than 16. The question notably excludes the real-world data from Israel and other analyses that Pfizer and the Biden administration had said would be a centerpiece of their arguments for boosters.

A Pfiz­er part­ner wel­comes ex-ADC Ther­a­peu­tics CMO Jay Fein­gold to the team; Amid tough sled­ding, Im­muno­vant choos­es Eli Lil­ly alum as CFO

→ Last week we told you about the CMO revolving door at ADC Therapeutics, as Joseph Camardo replaced the departing Jay Feingold. The next opportunity for Feingold in the CMO slot has opened up at antibody-drug conjugate and mAb developer Pyxis Oncology, which has added several new execs and scientific advisory board members in recent months, including ex-Immunovant CFO Pamela Yanchik Connealy. Before his tenure at ADC, Feingold was Daiichi Sankyo’s VP of US medical affairs and chairman of the Global Medical Affairs Oversight Committee. Within weeks in March, Pyxis struck a licensing deal with Pfizer for two of its ADCs and raked in $152 million from a Series B round.

Ali Tehrani, Zymeworks CEO

Zymeworks squares up with Her­ceptin af­ter HER2 bis­pe­cif­ic aces mid-stage test in esophageal can­cer

Roche’s Herceptin has long stood as standard of care across multiple advanced cancers, but a suite of next-gen players are looking to beat the aging giant at its own game. In HER2-expressing esophageal cancer, BeiGene partner Zymeworks thinks its bispecific antibody could have the juice to get it done.

Zymeworks’ bispecific antibody zanidatamab, combined with one of two chemotherapy regimens, posted an overall response rate of 75% in patients with advanced gastroesophageal adenocarcinoma (GEA) who had not previously received a HER2-targeted cancer therapy, the Vancouver-based biotech said Thursday.