Mer­ck high­lights cru­cial hit for Keytru­da in sec­ond-line esophageal car­ci­no­ma — but there are al­so 2 miss­es

Mer­ck has un­veiled a Phase III da­ta pack­age back­ing Keytru­da’s case as a sec­ond-line treat­ment for the tough in­di­ca­tions of esophageal and esoph­a­gogas­tric junc­tion car­ci­no­ma, un­der­scor­ing its ear­li­er con­fi­dence that the PD-1 in­hibitor rep­re­sents a sig­nif­i­cant ad­vance in this field de­spite on­ly hit­ting one of three pri­ma­ry end­points.

The key num­ber the com­pa­ny wants to fo­cus on is 31% — the de­gree by which Keytru­da re­duced the risk of death com­pared to chemother­a­py in pa­tients with squa­mous cell car­ci­no­ma or ade­no­car­ci­no­ma, who had pro­gressed af­ter stan­dard ther­a­py and whose tu­mors ex­pressed PD-L1 (as quan­ti­fied by a com­bined pos­i­tive score, or CPS, of 10 or above).

That sub­group, which con­sti­tutes 222 out of 628 to­tal pa­tients in the KEYNOTE-181 study, reached a me­di­an OS of 9.3 months ver­sus 6.7 months for the chemo group. They al­so had a 12-month OS rate of 43% while the chemo arm ex­pe­ri­enced 20%.

These are pa­tients whose can­cer — in the esoph­a­gus or the esoph­a­gogas­tric junc­tion — pro­gressed af­ter ini­tial treat­ment, fol­low­ing a poor prog­no­sis to be­gin with, re­searchers added.

For the en­tire in­ten­tion-to-treat pop­u­la­tion, though, the dif­fer­ence in OS be­tween two arms was not sta­tis­ti­cal­ly sig­nif­i­cant with a me­di­an OS of 7.1 months for both treat­ment groups. Same goes for the oth­er sub­group an­a­lyzed for the study — the 401 pa­tients with squa­mous cell car­ci­no­ma — with the Keytru­da group see­ing a me­di­an OS of 8.2 months com­pared to 7.1 months in those re­ceiv­ing chemo.

These fail­ures kept in­ves­ti­ga­tors from for­mal­ly test­ing the sec­ondary end­points, mean­ing that we won’t know the pro­gres­sion-free sur­vival and ob­jec­tive re­sponse rate.

Mean­while, a sep­a­rate Phase III study — dubbed KEYNOTE-590 — is putting the block­buster check­point in­hibitor to first-line use in com­bi­na­tion with chemother­a­py for pa­tients with esophageal car­ci­no­ma.

Ri­vals are lin­ing up their own shots at esophageal and esoph­a­gogas­tric can­cers, with late-stage of­fer­ings from chief ri­val Bris­tol-My­ers Squibb. Cel­gene and BeiGene, which were slat­ed to notch the 7th PD-1 ap­proval in the US, were al­so in the game, though the pro­gram’s fate re­mains un­clear as Bris­tol-My­ers com­pletes its $74 bil­lion ac­qui­si­tion of Cel­gene.

Grow­ing ac­cep­tance of ac­cel­er­at­ed path­ways for nov­el treat­ments: but does reg­u­la­to­ry ap­proval lead to com­mer­cial suc­cess?

By Mwango Kashoki, MD, MPH, Vice President-Technical, and Richard Macaulay, Senior Director, of Parexel Regulatory & Access

In recent years, we’ve seen a significant uptake in the use of regulatory options by companies looking to accelerate the journey of life-saving drugs to market. In 2018, 73% of the novel drugs approved by the U.S. Federal Drug Administration (FDA) were designated under one or more expedited development program categories (Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval).ᶦ

Sanofi out­lines big API plans as coro­n­avirus out­break re­port­ed­ly threat­ens short­age of 150 drugs

As the world becomes increasingly dependant on Asia for the ingredients of its medicines, Sanofi sees business to be done in Europe.

The French drugmaker said it’s creating the world’s second largest active pharmaceutical ingredients (API) manufacturer by spinning out its six current sites into a standalone company: Brindisi (Italy), Frankfurt Chemistry (Germany), Haverhill (UK), St Aubin les Elbeuf (France), Újpest (Hungary) and Vertolaye (France). They have mapped out €1 billion in expected sales by 2022 and 3,100 employees for the new operations headquartered in France.

Lessons for biotech and phar­ma from a doc­tor who chased his own cure

After being struck by a rare disease as a healthy third year medical student, David Fajgenbaum began an arduous journey chasing his own cure. Amidst the hustle of this year’s JP Morgan conference, the digital trials platform Medable partnered with Endpoints Studio to share Dr. Fajgenbaum’s story with the drug development industry.

What follows is an edited transcript of the conversation between Medable CEO Dr. Michelle Longmire and Dr. Fajgenbaum, and it is full of lessons for biotech executives charged with bringing the next generation of medicines to patients.

UP­DAT­ED: NGM Bio takes leap for­ward in crowd­ed NASH field

South San Francisco-based NGM Bio may have underwhelmed with its interim analysis of a key cohort from a mid-stage NASH study last fall — but stellar topline data unveiled on Monday showed the compound induced significant signs of antifibrotic activity, NASH resolution and liver fat reduction, sending the company’s stock soaring.

There are an estimated 50+ companies focused on developing drugs for non-alcoholic steatohepatitis, or NASH, a common liver disease that has long flummoxed researchers. The first wave of NASH drug developers struggled with efficacy as well as safety — and companies big and small have crashed and burned.

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Methicillin-resistant Staph aureus (Shutterstock)

FDA grants ‘break­through’ sta­tus to an­tibi­ot­ic al­ter­na­tive as Con­tra­Fect rush­es to join fight against su­per­bug

An experimental drug that promises to be the first anti-infective agent to prove superior to vancomycin — an antibiotic approved in 1958 — has notched the FDA’s “breakthrough” status.

ContraFect said the designation was based on Phase II data in which exebacase was tested against a superbug known as methicillin-resistant Staph aureus, or MRSA. In a subgroup analysis, the clinical responder rate at day 14 was 42.8% higher than that among those treated with standard of care, the company said (p=0.010).

Zhong Nanshan, CGTN via YouTube

Har­vard joins coro­n­avirus fight with $115 mil­lion and a high-pro­file Chi­nese part­ner

For two months, as the novel coronavirus swelled from a few early cases tied to a Wuhan market to a global epidemic, most of the world’s focus and dollars have flowed toward emergency initiatives: building vaccines at a record pace, plucking experimental antivirals out of freezers to see what sticks and immunizing mice for new antibodies.

Now a new and well-funded collaboration between Harvard and a top Chinese research institute will play the long game. In a 5-year, $115 million initiative backed by China Evergrande Group, researchers from the Harvard Medical School, Harvard T.H. Chan School of Public Health and Guangzhou Institute for Respiratory Health will study the virus in an effort to develop therapies against infections by the novel coronavirus, known as SARS–CoV-2, and to prevent new ones.

No­var­tis gets a boost in block­buster mul­ti­ple scle­ro­sis race with Roche

In the first step of what’s likely to be a long and uphill battle for the drugmaker, the FDA has accepted Novartis’s BLA submission for a new multiple sclerosis drug and given it priority review. The PDUFA date for the potential blockbuster drug is in June.

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Juergen Horn

An­i­mal health vet Juer­gen Horn makes new an­ti­body play for pets, rak­ing $15M in Se­ries A haul

Zoetis forked over $85 million in 2017 to acquire Nexvet Biopharma and its pipeline of monoclonal antibodies. Juergen Horn, Nexvet’s former chief product development officer, has now secured $15 million for his own biologic company for animals: Invetx.

Buoyed by emerging advances in gene therapies for humans, scientists have started looking at harnessing the technology for animals setting up companies such as Penn-partnered Scout Bio and George Church-founded Rejuvenate Bio. But akin to Nexvet, Invetx is working on leveraging the time-tested science of monoclonal antibodies to treat chronic diseases that afflict man’s best friend.

As coro­n­avirus out­break reach­es 'tip­ping point,' GSK lends ad­ju­vant tech to Chi­nese part­ner armed with pre­clin­i­cal vac­cine

As the coronavirus originating out of Wuhan spreads to South Korea, Italy and Iran, stoking already intense fears of a pandemic, GlaxoSmithKline has found another pair of trusted hands to place its adjuvant system. China’s Clover Biopharmaceuticals will add the adjuvant to its preclinical, protein-based vaccine candidate against SARS-CoV-2.

Clover, which is based in the inland city of Chengdu, boasts of a platform dubbed Trimer-Tag that produces covalently-trimerized fusion proteins. Its candidate, COVID-19 S-Trimer, resembles the viral spike (S)-protein found in the virus.