Sci­en­tists find un­ex­pect­ed an­ti-can­cer ac­tiv­i­ty in range of non-on­col­o­gy drugs — study

As the sec­ond lead­ing cause of mor­tal­i­ty glob­al­ly, the lu­cra­tive field of can­cer treat­ment has elicit­ed a fren­zy of drug de­vel­op­ment and bil­lions in ven­ture fund­ing. But a new study sug­gests that can­cer-killing com­pounds may be lurk­ing in the ex­ist­ing ar­se­nal of non-on­col­o­gy med­i­cines.

By an­a­lyz­ing thou­sands of FDA-ap­proved drugs and com­pounds that have been proven safe in clin­i­cal tri­als, sci­en­tists at the Broad In­sti­tute of MIT and Har­vard and Dana-Far­ber Can­cer In­sti­tute found near­ly 50 com­pounds — in­clud­ing drugs for di­a­betes, in­flam­ma­tion, al­co­holism and even a treat­ment for arthri­tis in dogs — with pre­vi­ous­ly un­de­tect­ed an­ti-can­cer ac­tiv­i­ty.

Todd Gol­ub

“We thought we’d be lucky if we found even a sin­gle com­pound with an­ti-can­cer prop­er­ties, but we were sur­prised to find so many,” said Todd Gol­ub, chief sci­en­tif­ic of­fi­cer and di­rec­tor of the Can­cer Pro­gram at the Broad, Charles A. Dana In­ves­ti­ga­tor in Hu­man Can­cer Ge­net­ics at Dana-Far­ber, and pro­fes­sor of pe­di­atrics at Har­vard Med­ical School, in a state­ment.

The study, pub­lished in the jour­nal Na­ture Can­cer, em­ployed the Broad’s Drug Re­pur­pos­ing Hub, an­a­lyz­ing 4,518 drugs against 578 hu­man can­cer cell lines from the Broad’s Can­cer Cell Line En­cy­clo­pe­dia. Af­ter tag­ging each cell line with a DNA bar­code, the re­searchers ex­posed each pool of bar­cod­ed cells to a sin­gle com­pound from the re­pur­pos­ing li­brary and mea­sured the sur­vival rate of can­cer cells.

Some of the can­cer-slay­ing com­pounds kill in un­fore­seen ways, study lead au­thor Steven Corsel­lo said. Corsel­lo is an on­col­o­gist at Dana-Far­ber and founder of the Drug Re­pur­pos­ing Hub.

Most ex­ist­ing can­cer drugs work by sti­fling pro­teins — but some of the can­cer-killing com­pounds Corsel­lo et al came across ap­peared to work by ac­ti­vat­ing a pro­tein or sta­bi­liz­ing a pro­tein-pro­tein in­ter­ac­tion. For ex­am­ple, the team found that near­ly a dozen non-on­col­o­gy drugs killed can­cer cells that ex­press a pro­tein called PDE3A by sta­bi­liz­ing the in­ter­ac­tion be­tween PDE3A and an­oth­er pro­tein called SLFN12.

Steven Corsel­lo

The re­sults of the analy­sis — which scoured near­ly half of all drugs ever test­ed in hu­mans — sug­gests that some non-on­col­o­gy drugs could be tak­en straight in­to clin­i­cal test­ing in can­cer pa­tients, al­though sci­en­tists will need to en­sure the can­cer culling ac­tiv­i­ty of these drugs is ob­served at con­cen­tra­tions that are tol­er­a­ble in hu­mans. It is al­so im­per­a­tive to con­firm that the pre­dic­tive bio­mark­ers iden­ti­fied in cell lines rep­re­sent dis­tinct pop­u­la­tions of hu­man tu­mors, the re­searchers cau­tioned.

“In con­trast to the repo­si­tion­ing of ex­ist­ing drugs for new in­di­ca­tions, the…re­sults re­port­ed here al­so rep­re­sent start­ing points for new drug de­vel­op­ment. In par­tic­u­lar, when the an­ti-can­cer ac­tiv­i­ty of a drug oc­curs via an off-tar­get mech­a­nism, it is like­ly that fur­ther op­ti­miza­tion for this new tar­get will re­sult in more po­tent and se­lec­tive drug can­di­dates,” the re­searchers wrote.

Re­pur­pos­ing drugs on pur­pose (or by ac­ci­dent) has yield­ed some suc­cess — that the process in­volves large­ly de-risked com­pounds, low­er de­vel­op­men­tal costs, and briefer time­lines don’t hurt ei­ther.

Aside from as­pirin’s car­dio­vas­cu­lar ben­e­fits, Vi­a­gra is an­oth­er heav­i­ly cit­ed ex­am­ple. The drug was orig­i­nal­ly be­ing test­ed as a treat­ment for coro­nary hy­per­ten­sion — but a pesky side ef­fect felt by pa­tients in tri­als cul­mi­nat­ed in its even­tu­al ap­proval as an erec­tile dys­func­tion drug.

Then there’s the seda­tive thalido­mide — which gained no­to­ri­ety af­ter its link to se­vere skele­tal birth de­fects trig­gered its with­draw­al in 1957. How­ev­er, years lat­er it was deemed ef­fec­tive as a can­cer treat­ment, even breed­ing the de­vel­op­ment and ap­proval of even more suc­cess­ful de­riv­a­tives, such as Cel­gene’s block­buster Revlim­id.

Mean­while, Mer­ck’s Vioxx — which was un­cer­e­mo­ni­ous­ly tak­en off shelves af­ter its link to dou­bling pa­tients’ risk of heart at­tack and stroke emerged — could resur­face as a gener­ic treat­ment for a side ef­fect ex­pe­ri­enced by he­mo­phil­ia pa­tients.

But akin to tra­di­tion­al drug de­vel­op­ment, drug re­pur­pos­ing has al­so seen its share of set­backs. Two ex­am­ples of late-stage fail­ures in­clude a bid to use the an­ti­his­t­a­mine, la­trepir­dine, as a treat­ment for Hunt­ing­ton’s dis­ease, as well as the pur­suit of re­pur­pos­ing the an­tibi­ot­ic, cef­tri­ax­one, as a med­i­cine for ALS.

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.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 72,900+ biopharma pros reading Endpoints daily — and it's free.

Mickey Kertesz, KidsandArtOrg via YouTube

Soft­Bank's newest, $165M biotech in­vest­ment looks for in­fec­tious traces in the blood

SoftBank has found its newest biotech investment.

The Japanese bank has invested $165 million into Karius, a company that uses blood tests to diagnose infectious diseases, as part of its new Vision Fund 2. The full scope of the new fund has yet to be announced, but the first and newly-beleaguered Vision Fund poured $100 billion into technology companies, including the biotechs Vir Biotechnology and Roivant and the sequencing company 10x Genomics.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 72,900+ biopharma pros reading Endpoints daily — and it's free.

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.