Hung ju­ry vote leaves FDA with a dif­fi­cult de­ci­sion on Durec­t's non-opi­oid painkiller

A split ad­vi­so­ry pan­el vote on Durect’s non-opi­oid drug to man­age post-sur­gi­cal pain is on­ly go­ing to make the FDA’s task hard­er.

Af­ter FDA staff re­view­ers is­sued an in­ter­nal re­view that un­der­scored their un­ease with the side-ef­fect pro­file of the long-act­ing anes­thet­ic posimir — on Thurs­day a pan­el of in­de­pen­dent ex­perts could not reach a con­sen­sus on whether to back the ther­a­py.

Six pan­elists en­dorsed ap­proval, while the re­main­ing six dis­sent­ed. The ther­a­py is a for­mu­la­tion of the anes­thet­ic bupi­va­caine and is de­signed to man­age pain up to three days fol­low­ing surgery af­ter be­ing ad­min­is­tered di­rect­ly in­to the sur­gi­cal in­ci­sion.

Posimir has a check­ered past. Durect, which orig­i­nal­ly part­nered with No­var­tis on the pro­gram, first sub­mit­ted an ap­pli­ca­tion to mar­ket on the ba­sis of two piv­otal stud­ies. The FDA spurned the ap­pli­ca­tion in 2014 over safe­ty con­cerns. Durect then con­duct­ed the PER­SIST study, hop­ing to quell the agency’s con­cerns — but that tri­al failed its main ef­fi­ca­cy goal. Nonethe­less, Durect re­sub­mit­ted a mar­ket­ing ap­pli­ca­tion.

The US drug reg­u­la­tor has in­ten­si­fied its ef­forts to stem the tide of opi­oid abuse, over­dose, and ad­dic­tion, fierce­ly scru­ti­niz­ing the phar­ma­ceu­ti­cal ar­chi­tects of the pre­scrip­tion painkiller cri­sis. So de­spite per­sis­tent safe­ty con­cerns as­so­ci­at­ed with posimir, the prospect of ‘opi­oid-spar­ing’ was ap­peal­ing to some pan­elists.

“The da­ta was in­con­sis­tent and there are some un­knowns that don’t make sense with the ra­tio­nale I heard,” said Joseph O’Brien, chief of Mass­a­chu­setts-based Na­tion­al Sco­l­io­sis Foun­da­tion, who en­dorsed posimir.”De­spite all these con­cerns, at the end of the day, we do have a need for opi­oid-spar­ing med­ica­tion,” he said, as cit­ed by Reuters.

Pan­elists against ap­proval ex­pressed their un­ease with posimir’s ef­fi­ca­cy, with some sug­gest­ing the ther­a­py’s du­ra­tion of ac­tion was lim­it­ed to 12 to 24 hours, echo­ing the FDA staff re­view is­sued on Tues­day. Con­cerns about safe­ty lin­gered with pan­elists on ei­ther side of the vote, and some sug­gest­ed ad­di­tion­al stud­ies were war­rant­ed to demon­strate res­cue in the event of ac­ci­den­tal in­tra­venous ad­min­is­tra­tion.

A 50/50 split vote is rare. Last year, a pill for pa­tients with the less com­mon type 1 di­a­betes, who pro­duce no in­sulin, was the sub­ject of an atyp­i­cal hung ju­ry vote at an FDA pan­el. Ex­perts were di­vid­ed even­ly over whether the life-threat­en­ing risk of di­a­bet­ic ke­toaci­do­sis as­so­ci­at­ed with the drug, so­tagliflozin, off­set its ben­e­fit — the FDA even­tu­al­ly re­ject­ed the di­a­betes ther­a­py.

Some pan­elists de­lib­er­at­ing on posimir seemed more open to con­sid­er­ing the ther­a­py’s da­ta as ev­i­dence of opi­oid-spar­ing com­pared to a No­vem­ber 2018 Ad­Com on opi­oid-spar­ing end­points, Cowen’s Boris Peak­er wrote in a note, which drew com­par­isons be­tween posimir and two oth­er bupi­va­caine painkillers: HTX-011 from Heron $HRTX and Ex­par­el from Paci­ra $PCRX.

“De­spite the ques­tion­able da­ta, the ‘yes’ votes were pri­mar­i­ly dri­ven by the time to opi­oid res­cue da­ta,” Peak­er wrote. “If time to opi­oid res­cue does be­come a sig­nif­i­cant end­point, HRTX’s da­ta ap­pears to be stronger than PCRX in cross-tri­al com­par­i­son. As such, we see this as an­oth­er op­por­tu­ni­ty for HTX-011 dif­fer­en­ti­a­tion vs. Ex­par­el.”

Paci­ra’s J&J-part­nered, long-act­ing post-op bupi­va­caine painkiller Ex­par­el gen­er­at­ed net sales of about $331 mil­lion in 2018. Heron’s HTX-011 — a for­mu­la­tion of bupi­va­caine and the non-steroidal an­ti-in­flam­ma­to­ry drug (NSAID) meloxi­cam — re­ceived an un­ex­pect­ed re­jec­tion due to man­u­fac­tur­ing con­cerns last year, but is on track to se­cure ap­proval by March.

Ear­li­er in the week, af­ter an FDA ad­vi­so­ry com­mit­tee vot­ed unan­i­mous­ly against Nek­tar Ther­a­peu­tics opi­oid painkiller — a for­mu­la­tion not en­gi­neered to fa­cil­i­tate abuse de­ter­rence from phys­i­cal ma­nip­u­la­tion — the com­pa­ny aban­doned the drug.

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.