An­oth­er cheap, old drug is be­ing fresh­ened up for brand pric­ing in the US — and shares soar, briefly

BioReg­num, the view from John Car­roll

When the ex­ecs at Fortress went about set­ting up their pain drug biotech Av­enue Ther­a­peu­tics $ATXI, they went to some ex­tremes to avoid R&D risk. In­stead of try­ing some­thing new, they tweaked a Eu­ro­pean IV for­mu­la­tion for tra­madol — nev­er ap­proved in the US, where oral tra­madol has been pre­scribed for 23 years — and took a shot at a piv­otal pro­gram.

To get start­ed, the com­pa­ny paid a grand to­tal of $3 mil­lion — in two stag­gered pay­ments — for the rights to an old, well un­der­stood and quite pow­er­ful gener­ic pain med, with mile­stones at­tached to their suc­cess.

That qual­i­fies as lunch mon­ey in the bio­phar­ma busi­ness.

Lucy Lu

More ex­pen­sive — but still rel­a­tive­ly cheap — was a piv­otal de­vel­op­ment pro­gram they reck­oned would cost $30 mil­lion when Av­enue pitched its S-1 to in­vestors. Rolled out at a pro­posed $10 a share, they took $6 at the pric­ing, raised $33 mil­lion for the re­search and saw the price surge to about $8 be­fore grad­u­al­ly de­scend­ing to a lit­tle more than $4 a share.

The mar­ket cap closed at a mi­cro lev­el of $44 mil­lion on Fri­day.

Which brings us to to­day. 

Av­enue is an­nounc­ing that the first piv­otal study, com­par­ing IV tra­madol to a place­bo, was a suc­cess, with a p-val­ue of 0.005 for the 50 mg dose. Three sec­ondary end­points al­so hit on the 50 mg. They’re hold­ing back the de­tails on the da­ta for a con­fer­ence and plan to start the sec­ond, con­fir­ma­to­ry Phase III lat­er this year.

Av­enue’s ex­ecs went in­to the study with the odds on their side. Tra­madol’s ef­fec­tive­ness is so well un­der­stood, it’s be­gun rais­ing con­cerns about be­com­ing the poor man’s opi­oid in oth­er coun­tries. The DEA des­ig­nat­ed the syn­thet­ic anal­gesic as a Sched­ule IV drug in 2015. So I asked Av­enue CEO Lucy Lu about that by email, and whether the com­pa­ny was sim­ply set­ting up a shot at charg­ing a pre­mi­um in the US for an­oth­er old gener­ic run by the reg­u­la­tors — al­beit af­ter a fair­ly sig­nif­i­cant de­vel­op­ment pro­gram.

Her re­sponse:

The FDA re­quires two place­bo-con­trolled stud­ies be­cause it’s not nec­es­sar­i­ly easy to beat place­bo in a pain study and on­ly tru­ly ef­fi­ca­cious drugs can do that. In our case, IV tra­madol beat place­bo not on­ly on the pri­ma­ry end­point, but al­so all of the key sec­ondary end­points, in­clud­ing pa­tient glob­al as­sess­ment, in a very con­sis­tent and dose de­pen­dent man­ner. In com­bi­na­tion with what we know about oral tra­madol, it points to a very ef­fec­tive IV drug.

We have not done a de­tailed pric­ing study. How­ev­er, all of the spon­sors in our space that have dis­cussed pric­ing of new drugs have men­tioned around $100 per day. I think that pro­vides a use­ful bench­mark.

Gener­ic tra­madol pills cost about $1.50 each.

In­vestors liked the sound of it all. Av­enue’s shares jumped 29% in pre-mar­ket trad­ing. But then peo­ple be­gan to think about it, and the shares end­ed down the day about 4%. It is, af­ter all, not the kind of sto­ry that peo­ple are at­tract­ed to.

There’s noth­ing new about grab­bing an old drug OK’d in Eu­rope and then bring­ing it in cheap years lat­er for the US mar­ket. Marathon did that with a steroid, de­vel­oped specif­i­cal­ly for Duchenne, which it then rolled out as an ex­pen­sive rare dis­ease drug — un­til the whole sit­u­a­tion blew up in­to a con­tro­ver­sy that forced the com­pa­ny to sell it to PTC. Marathon ex­ecs were Mar­tin Shkre­li’s role mod­el in drug de­vel­op­ment.

You can de­cide for your­self if Av­enue is gam­ing the sys­tem.

Charles Baum, Mirati CEO

UP­DAT­ED: Mi­rati plots a march to the FDA for its KRAS G12C drug, breath­ing down Am­gen’s neck with bet­ter da­ta

Mirati Therapeutics $MRTX took another closely-watched step toward a now clearly defined goal to file for an approval for its KRAS G12C cancer drug adagrasib (MRTX849), scoring a higher response rate than the last readout from the class-leading rival at Amgen but still leaving open a raft of important questions about its future.

Following a snapshot of the first handful of responses, where the drug scored a tumor response in 3 of 5 patients with non-small cell lung cancer, the response rate has now slid to 45% among a pooled group of 51 early-stage and Phase II patients, 43% — 6 of 14 — when looking solely at the Phase I/Ib. Those 14 patients had a median treatment duration of 8.2 months, with half still on therapy and 5 of 6 responders still in response.

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In his­toric Covid-19 ad­comm, vac­cine ex­perts de­bate a sea of ques­tions — but of­fer no clear an­swers

The most widely anticipated and perhaps most widely watched meeting in the FDA’s 113-year history ended late Thursday night with a score of questions and very few answers.

For nearly 9 hours, 18 different outside experts listened to public health agencies and foundations present how the United States’ Covid-19 vaccine program developed through October, and they debated where it should go from there: Were companies testing the right metrics in their massive trials? How long should they track patients before declaring a vaccine safe or effective? Should a vaccine, once authorized, be given to the volunteers in the placebo arm of a trial?

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Michel Vounatsos, Biogen CEO (via YouTube)

Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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A top drug pro­gram at Bay­er clears a high bar for CKD — open­ing the door to an FDA pitch

Over the past 4 years, Bayer has been steering a major trial through a pivotal program to see if their drug finerenone could slow down the pace of chronic kidney disease in patients suffering from both CKD as well as Type 2 diabetes.

Today, their team jumped on a virtual meeting hosted by the American Society of Nephrology to offer a solid set of pivotal data to demonstrate that the drug can delay dialysis or a kidney replacement as well as cardio disease, while also adding some worrying signs of hyperkalemia among the patients taking the drug. And they’re hustling it straight to regulators in search of an approval for kidney disease and cardio patients — one of the toughest challenges in the book, as demonstrated by repeated past failures.

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Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

Setting the stage for an extraordinary one-day meeting of the Vaccines and Related Biological Products Advisory Committee this Thursday, the FDA has cleared 2 experts of financial conflicts to help beef up the committee. And regulators went on to specify the safety, efficacy and CMC input they’re looking for on EUAs, before they move on to the full BLA approval process.

All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

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CRISPR Ther­a­peu­tics gets a snap­shot of off-the-shelf CAR-T suc­cess in B-cell ma­lig­nan­cies — marred by the death of a pa­tient

Just days after scientific founder Emmanuelle Charpentier shared the Nobel prize for her work on CRISPR/Cas9, CRISPR Therapeutics $CRSP is showing off a snapshot of success in their early-stage study for an off-the-shelf CAR-T approach to CD19+ B cell malignancies — a snapshot marred by the death of a patient who had been given a high dose of the treatment.

Using their gene editing tech, researchers for CRISPR engineered cells from healthy donors into an attack vehicle aimed at cancer, something that has been achieved with great success using patients’ own cells — the autologous approach. But autologous CAR-T is hampered by the more complex vein-to-vein requirement that delays treatment, and now CRISPR Therapeutics along with other players like Allogene are determined to replace the pioneers with CAR-T 2.0.

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Biond­Vax stock im­plodes af­ter a big PhI­II gam­ble for its uni­ver­sal flu vac­cine fails

After flying high on Wall Street for the last few months of a pandemic, BiondVax’s stock and dreams of getting approval for its universal flu vaccine hit the windshield.

The Jerusalem-based biotech announced on Friday that its only clinical candidate, M-001, failed both primary and secondary endpoints in a Phase III study. There was no statistically significant difference in reduction of flu illness and severity between the vaccine and placebo groups, according to the company. The vaccine did prove safe, if ineffective, BiondVax said.

Pascal Soriot, AstraZeneca CEO (Zach Gibson/Bloomberg via Getty Images)

UP­DAT­ED: FDA gives As­traZeneca the thumbs-up to restart PhI­II Covid-19 vac­cine tri­als, and J&J is prepar­ing to re­sume its study

Several countries had restarted their portions of AstraZeneca’s global Phase III Covid-19 vaccine trial after the study was paused worldwide in early September, but the US notably stayed on the sidelines — until now. Friday afternoon the pharma giant announced the all clear from US regulators. And on top of that, J&J announced Friday evening that it’s preparing to resume its own Phase III vaccine trial.

Ul­tragenyx in­jects $40M to grab Solid's mi­crody­s­trophin trans­gene — while side­step­ping the AAV9 vec­tor that stirred up safe­ty fears

Since before Ilan Ganot started Solid Bio to develop a gene therapy for kids like his son, who has Duchenne muscular dystrophy, Ultragenyx CEO Emil Kakkis has been watching and advising the former investment banker as he navigated the deep waters of drug development.

Just as Solid is getting back up on its feet after a yearlong clinical hold, Kakkis has decided to jump in for a formal alliance.

With a $40 million upfront, Ultragenyx is grabbing 14.45% of Solid’s shares $SLDB and the rights to its microdystrophin construct for use in combination with AAV8 vectors. Solid’s lead program, which utilizes AAV9, remains unaffected. The company also retains rights to other applications of its transgene.