Failed piv­otal study? You can still have break­through ther­a­py sta­tus — FDA sig­nals to Resver­logix

A small Cana­di­an biotech­nol­o­gy com­pa­ny has con­vinced the FDA to re­ward its sole ex­per­i­men­tal drug break­through ther­a­py sta­tus as a pre­ven­ta­tive ther­a­py for ma­jor ad­verse car­diac events, de­spite a failed late-stage study.

Last Sep­tem­ber, Cal­gary, Al­ber­ta-based Resver­logix Corp said its in­ves­ti­ga­tion­al apa­betalone did not meet the main piv­otal study goal of re­duc­ing ma­jor ad­verse car­dio­vas­cu­lar events (MACE) — de­fined as car­dio­vas­cu­lar death, non-fa­tal my­ocar­dial in­farc­tion, and stroke — when added to stan­dard care in pa­tients with type II di­a­betes, re­cent acute coro­nary syn­drome, and low HDL cho­les­terol.

Apa­betalone is a se­lec­tive in­hibitor of the BET fam­i­ly of pro­teins that play a role in the reg­u­la­tion of cell growth, dif­fer­en­ti­a­tion, and in­flam­ma­tion. BET in­hi­bi­tion is an epi­ge­net­ic mech­a­nism — and the drug is de­signed to re­store bi­o­log­i­cal func­tions, al­tered by se­ri­ous ill­ness­es, back to a healthy state.

If DNA is the hard­ware, epi­ge­net­ics is the soft­ware. DNA con­tains the code that dic­tates what cells do — while epi­ge­net­ic changes mod­u­late the ef­fect of those mes­sages, like a dim­mer switch telling cells which pro­teins to make more of and where to lim­it pro­tein pro­duc­tion.

De­tailed da­ta from the 2,425-pa­tient, place­bo-con­trolled Phase III tri­al — dubbed BE­Ton­MACE — were dis­closed in No­vem­ber. The re­sults showed the MACE find­ings on the apa­betalone arm were 10.3%, while the place­bo pa­tients chalked up 12.4% (p = 0.11). All oth­er sec­ondary goals, apart from stroke, fa­vored the drug but did not in­duce a sta­tis­ti­cal­ly sig­nif­i­cant ef­fect.

Kausik Ray Im­pe­r­i­al Col­lege Lon­don

Kausik Ray, the BE­Ton­MACE study chair and pro­fes­sor of pub­lic health and con­sul­tant car­di­ol­o­gist at Im­pe­r­i­al Col­lege Lon­don, sug­gest­ed that while apa­betalone was not found su­pe­ri­or to place­bo — the drug “on­ly just missed sta­tis­ti­cal sig­nif­i­cance” and it ap­peared that the tri­al was “a bit un­der­pow­ered to show a ben­e­fit due to low­er than ex­pect­ed event rates.”

“Giv­en the promis­ing signs…we think this (drug) holds con­sid­er­able promise, and per­haps a slight­ly larg­er study with a few more events would al­low us to as­sess more ro­bust­ly whether this drug will pro­vide a 20% treat­ment ef­fect in this pa­tient pop­u­la­tion,” he said in an in­ter­view with the Amer­i­can Heart As­so­ci­a­tion.

As for Resver­logix, it is con­vinced the ex­per­i­men­tal ther­a­py works. On its web­site the com­pa­ny says:

“From da­ta col­lect­ed in our clin­i­cal tri­als, we now know that apa­betalone – through its ef­fects on epi­ge­net­ics – ben­e­fits mul­ti­ple process­es which con­tribute to the on­set and wors­en­ing of dis­ease. This is con­sis­tent with ob­served re­duc­tions in ma­jor ad­verse car­diac events (MACE) in study par­tic­i­pants. Pa­tients who take apa­betalone have few­er heart at­tacks, strokes, and car­diac-re­lat­ed deaths.”

On Mon­day, the FDA grant­ed the drug break­through sta­tus in com­bi­na­tion with stan­dard care for the sec­ondary pre­ven­tion of ma­jor ad­verse car­diac events in pa­tients with type II di­a­betes mel­li­tus and re­cent acute coro­nary syn­drome.

Heart dis­ease — the lead­ing killer in de­vel­oped na­tions (al­though can­cer is catch­ing up) — is a lu­cra­tive bat­tle­ground for drug­mak­ers big and small, al­though the field is lit­tered with fail­ure.

Resver­logix is al­so test­ing apa­betalone in pa­tients with Fab­ry dis­ease.

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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.

Mickey Kertesz, KidsandArtOrg via YouTube

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SoftBank has found its newest biotech investment.

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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.

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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.

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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.