Man­u­fac­tur­ing is­sues hob­ble Heron's quest to mar­ket its long-act­ing non-opi­oid painkiller

The C-suite at Paci­ra like­ly sighed in re­lief on Wednes­day, as their main ri­val, Heron Ther­a­peu­tics, was hand­ed an un­ex­pect­ed FDA re­jec­tion — re­lat­ed to man­u­fac­tur­ing con­cerns — for a com­pet­ing long-act­ing non-opi­oid painkiller for post-sur­gi­cal anal­ge­sia.

The health reg­u­la­tor has asked for ad­di­tion­al in­for­ma­tion re­lat­ed to Heron’s chem­istry, man­u­fac­tur­ing and con­trols and oth­er non-clin­i­cal da­ta — and has not iden­ti­fied any safe­ty or ef­fi­ca­cy is­sues, nor asked for ex­tra clin­i­cal stud­ies and da­ta analy­ses for the drug, HTX-011, Heron said.

Paci­ra in­vestors cheered the an­nounce­ment, lift­ing the com­pa­ny’s stock $PCRX more than 16% to $46.25 be­fore the bell. Mean­while, Heron shares $HRTX tum­bled more than 26% to $16.01 pre­mar­ket.

Heron plans to li­aise with the FDA to re­solve their con­cerns, and re­sub­mit its mar­ket­ing ap­pli­ca­tion as soon as pos­si­ble, chief Bar­ry Quart said in a state­ment.

The man­u­fac­tur­ing is­sues are like­ly solv­able, Cowen an­a­lysts wrote in a note, pre­dict­ing a new FDA de­ci­sion date in first half of next year.

As the US health reg­u­la­tor per­sists in its ef­fort to stem the tide of opi­oid abuse, over­dose and ad­dic­tion while the phar­ma­ceu­ti­cal ar­chi­tects of the pre­scrip­tion painkiller cri­sis face fierce scruti­ny, Heron Ther­a­peu­tics had de­signed the drug to take a bite out of the mar­ket that en­com­pass­es mil­lions of post­op­er­a­tive pa­tients who are can­di­dates for opi­oids. HTX-011 has shown in stud­ies to sub­due the need for opi­ates.

Heron is ini­tial­ly tar­get­ing rough­ly 13.5 mil­lion pa­tients who have un­der­gone the most painful pro­ce­dures (typ­i­cal­ly gen­er­al surgery, OB/GYN and plas­tic surgery). Many of these pa­tients are first giv­en a lo­cal anes­thet­ic like bupi­va­caine to dull the pain, but the ef­fects on­ly last about six hours or so, there­fore doc­tors tend to pre­scribe opi­oids to man­age se­vere pain that can last up to three days (de­pend­ing on the surgery).

HTX-011 is de­signed to slow­ly re­lease its two in­gre­di­ents: bupi­va­caine and the non-steroidal an­ti-in­flam­ma­to­ry drug (NSAID) meloxi­cam over a three-day pe­ri­od.

Bar­ry Quart

When you cut through tis­sue, and some­times bone, in­flam­ma­to­ry cy­tokines are re­leased. Apart from the in­flam­ma­tion that aris­es in re­sponse, these cy­tokines change the lo­cal PH of the in­ci­sion, mak­ing it more acidic (lo­cal anes­thet­ics tend to lose their po­ten­cy in acidic en­vi­ron­ments), and en­hance the sen­si­tiv­i­ty of nerve end­ings so even low lev­els of pain pro­duce a larg­er pain trans­mis­sion to the brain, Quart ex­plained in an in­ter­view with End­points News ahead of the FDA de­ci­sion.

“Adding a small amount of the NSAID meloxi­cam in­to our poly­mer for­mu­la­tion and re­leas­ing that si­mul­ta­ne­ous­ly over three days al­lowed us to block enough of that in­flam­ma­to­ry process,” Quart said. “We can show clear pain re­duc­tion for the full three days that the drug (HTX-011) is be­ing re­leased. It’s the first time — that we know of — that an ex­tend­ed-re­lease lo­cal anes­thet­ic of any kind re­gard­less of how its de­liv­ered has been able to beat bupi­va­caine so­lu­tion as stan­dard-of-care in large Phase III tri­als.”

Com­bin­ing HTX-011 with two over-the-counter oral anal­gesics (ac­eta­minophen and ibupro­fen) has yield­ed im­pres­sive re­sults in help­ing post-op pain pa­tients re­main opi­oid free in two stud­ies pub­lished by Heron this year.

In a 63-pa­tient study, 90% of pa­tients re­ceiv­ing HTX-011 with the OTC anal­gesic reg­i­men did not re­quire opi­oids to man­age their post­op­er­a­tive pain through 72 hours post her­nia surgery, com­pared to 51%, 40% and 22% of pa­tients re­ceiv­ing HTX-011, bupi­va­caine and a place­bo, Heron re­vealed in Jan­u­ary. Fol­low up af­ter 28 days showed 81% of pa­tients re­mained opi­oid-free.

Biren Amin

“We con­sid­er these re­sults as com­pelling, and sup­port­ing a best-in-class pro­file in post-op pain based on sig­nif­i­cant­ly more opi­oid-free pa­tients and sub­stan­tial­ly low­er opi­oid use. HTX-011 could of­fer the on­ly op­tion of opi­oid-free pre­scrip­tion at dis­charge, which re­mains a high pri­or­i­ty in the bat­tle against opi­oid abuse,” Jef­feries’ Biren Amin wrote in a note that month.

Apart from bupi­va­caine, HTX-011 will com­pete with Paci­ra Phar­ma­ceu­ti­cals’ J&J-part­nered, long-act­ing post-op painkiller Ex­par­el, which gen­er­at­ed net sales of about $331 mil­lion last year. Ex­par­el’s main in­gre­di­ent is al­so bupi­va­caine and the drug has been ap­proved by the US reg­u­la­tor since Oc­to­ber 2011 as a treat­ment for post­sur­gi­cal anal­ge­sia.

In a note pub­lished in March, SVB Leerink an­a­lysts wrote that while “Ex­par­el does a good job re­duc­ing opi­oid use for post-op pain; HTX-011 could do this bet­ter,” cit­ing a KOL sur­vey. “…it (Ex­par­el) has done a good job in re­duc­ing opi­oid use and hos­pi­tal­iza­tion time in its post-op­er­a­tive pa­tients, the du­ra­tion of ef­fi­ca­cy is in the 24-36 hour range. As such, this KOL be­lieves the longer po­ten­tial du­ra­tion of ef­fi­ca­cy and the in­stil­la­tion method of HTX-011 will re­sult in ini­tial use of the prod­uct. But up­on avail­abil­i­ty of both prod­ucts, this KOL be­lieves hos­pi­tals will run their own pi­lot stud­ies in var­i­ous sur­gi­cal mod­els to see how they com­pare to one an­oth­er.”

Over half the pa­tients Heron is tar­get­ing are re­ceiv­ing bupi­va­caine, and about 4% are get­ting Ex­par­el — the rest are get­ting var­i­ous “caines” such as li­do­caine, Quart said. “While we ob­vi­ous­ly ex­pect to take a cer­tain part of Ex­par­el mar­ket share…our pri­ma­ry tar­get is the 96% of pa­tients who are re­ceiv­ing…short-act­ing lo­cal anaes­thet­ics.”

Paci­ra, which un­veiled plans to swal­low a com­pa­ny that makes a sys­tem that us­es in­tense­ly cold ther­a­py on a spe­cif­ic nerve to re­lieve pain to com­ple­ment its flag­ship Ex­par­el treat­ment and for­ti­fy its pain fran­chise in March, is set to re­port is first-quar­ter re­sults on Thurs­day.

Year-on-year Ex­par­el rev­enue growth for 2019 is es­ti­mat­ed at 23%, Jef­feries an­a­lysts pre­dict­ed in a note last week. “(D)es­pite the strong re­cent (Ex­par­el) re­sults…cur­rent pen­e­tra­tion rates re­main very low…and the mar­ket is cer­tain­ly large enough to ac­com­mo­date two or more play­ers. In fact, we think the ad­di­tion­al voice of an­oth­er mar­ket­ing team rais­ing aware­ness for non-opi­oid post-sur­gi­cal pain op­tions ar­guably helps all mar­ket par­tic­i­pants. And per­haps most im­por­tant­ly, we view the sit­u­a­tion as less like ‘Coke vs Pep­si’ and more to the point that if un­bundling and ac­cess con­tin­ue to im­prove, all com­peti­tors in the seg­ment ben­e­fit.”

In a stun­ning set­back, Amarin los­es big patent fight over Vas­cepa IP. And its high-fly­ing stock crash­es to earth

Amarin’s shares $AMRN were blitzed Monday evening, losing billions in value as reports spread that the company had lost its high-profile effort to keep its Vascepa patents protected from generic drugmakers.

Amarin had been fighting to keep key patents under lock and key — and away from generic rivals — for another 10 years, but District Court Judge Miranda Du in Las Vegas ruled against the biotech. She ruled that:
(A)ll the Asserted Claims are invalid as obvious under 35 U.S.C.§ 103. Thus, the Court finds in favor of Defendants on Plaintiff’s remaining infringementclaim, and in their favor on their counterclaims asserting the invalidity of the AssertedClaims under 35 U.S.C. § 103.

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UP­DAT­ED: Have a new drug that promis­es to fight Covid-19? The FDA promis­es fast ac­tion but some de­vel­op­ers aren't hap­py

After providing an emergency approval to use malaria drugs against coronavirus with little actual evidence of their efficacy or safety in that setting, the FDA has already proven that it has set aside the gold standard when it comes to the pandemic. And now regulators have spelled out a new approach to speeding development that promises immediate responses in no uncertain terms — promising a program offering the ultimate high-speed pathway to Covid-19 drug approvals.

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On Tuesday, Southampton, UK-based startup Synairgen kicked off a mid-stage placebo-controlled study testing its experimental drug, SNG001 — an inhaled formulation of interferon-beta-1a — that has previously shown to be safe and effective in improving lung function in asthma patients with a respiratory viral infection in a pair of Phase II trials.

Once fu­ri­ous over No­var­tis’ da­ta ma­nip­u­la­tion scan­dal, the FDA now says it’s noth­ing they need to take ac­tion on

Back in the BP era — Before Pandemic — the FDA ripped Novartis for its decision to keep the agency in the dark about manipulated data used in its application for Zolgensma while its marketing application for the gene therapy was under review.

Civil and criminal sanctions were being discussed, the agency noted in a rare broadside at one of the world’s largest pharma companies. Notable lawmakers cheered the angry regulators on, urging the FDA to make an example of Novartis, which fielded Zolgensma at $2.1 million — the current record for a one-off therapy.

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Covid-19 roundup: GSK, Am­gen tai­lor R&D work to fit the coro­n­avirus age; Doud­na's ge­nomics crew launch­es di­ag­nos­tic lab

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Following in the footsteps of a lineup of big players like Eli Lilly — which has suspended patient recruitment for drug studies — Amgen and GSK have opted to take a more tailored approach. Amgen is intent on circling the wagons around key studies that are already fully enrolled, and GSK has the red light on new studies while the pandemic plays out.

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‘There was a grow­ing weari­ness’: Rush­ing against a pan­dem­ic clock, As­pen Neu­ro­sciences se­cures $70M Se­ries A

Just before Christmastime, Howard Federoff got a tip from Washington: There was a new virus in China. And this one could be bad.

News report of the virus had not yet appeared. Federoff, a neuroscientist, was briefed because years before, he was vetted as part of a group — he didn’t give a name for the group — to consult for the US government on emerging scientific issues. His day job, though, was CEO of Aspen Neurosciences, a Parkinson’s cell therapy startup that days before had come out of stealth mode and gave word to investors they were hoping to raise $70 million. That, Federoff realized, would be difficult if a pandemic shut down the global economy.

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With a PDUFA date of September 30, the journey of the drug — remestemcel-L, or Ryoncil — could shed light on the agency’s capacity to facilitate drug development unrelated to Covid-19.

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President Trump has a new favorite Covid-19 drug.

After a conversation with Japanese Prime Minister Shinzo Abe, Politico reports, the president is pressuring the FDA to issue emergency use authorization for favipiravir, a flu drug that showed glimpses of success in China but remains unproven and carries a list of worrying side effects. The push comes after a week-plus in which the White House touted a potentially effective but unproven malaria medication despite the concerns of scientific advisors such as NIAID director Anthony Fauci. And Trump ally Rudy Giuliani has been talking up unproven cell therapy efforts on Twitter.

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ITeos nabs $125M as they prep Keytru­da com­bi­na­tion tri­al — if Covid-19 will let them

For iTeos, it turned out, $75 million could only last so long.

Two years after announcing their eye-catching Series B raise, the Belgian biotech is back with an even larger Series B-2: $125 million.

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