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.”

The breakthrough therapy designation Pfizer and Merck KGaA notched for Bavencio in bladder cancer has quickly paved way for a full approval.

The PD-L1 drug is now sanctioned as a first-line maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma, applicable in cases where cancer hasn’t progressed after platinum-containing chemotherapy.

Petros Grivas, the principal investigator of the supporting Phase III JAVELIN Bladder 100, called the approval “one of the most significant advances in the treatment paradigm in this setting in 30 years.”

Merck has notched an approval for using Keytruda to treat a biomarker-based subset of first-line colorectal cancer patients with unresectable or metastatic tumors, as the pharma giant continues to find new niches for its blockbuster PD-1 star.

The OK is significant in a number of ways. Not only does it build on an accelerated approval for all tumors characterized as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR); it also marks the first single treatment for colorectal cancer that doesn’t contain chemotherapy.

Novartis has reached another large settlement to resolve misconduct allegations, agreeing to pay more than $678 million to settle claims that it had spent hundreds of millions of dollars on lavish dinners, so-called speaking fees and expensive alcohol “that were nothing more than bribes” to get doctors to prescribe Novartis medications.

The top-shelf alcohol and lavish meals included a $3,250 per person night at Nobu in Dallas, a $672-per person dinner at Washington DC’s Smith & Wollensky and a $314 per person meal at Sushi Roku in Pasadena, according to the Justice Department complaint. There were at least 7 trips to Hooters and fishing trips in Alaska and off the Florida coast. Each of these events were supposed to be “speaker programs” where doctors educated other doctors on a drug, but the DOJ alleged many were “bogus” wine-and-dine events where the drug was barely mentioned, if at all.  (“Nobody presented slides on the fishing trips,” the complaint says.)

A new court ruling has strengthened Amgen’s grip on the IP estate around Enbrel, keeping biosimilars of the autoimmune and inflammatory drug at bay until 2029.

Novartis, the patent challenger, isn’t throwing in the towel yet. In a statement noting the failed appeal, its generics division Sandoz noted its reviewing options, “including potential appeal to US Supreme Court.”

It’s been almost four years since the FDA approved Erelzi, Sandoz’s copycat version of Enbrel. While sales of the Pfizer-partnered drug in the US — the market Amgen is in charge of — have dipped slightly during that time, it remains a solid megablockbuster with 2019 revenue slightly above $5 billion.