Imara at­tempts to spin weak da­ta in­to an 'en­cour­ag­ing' re­sult — but in­vestors aren't hav­ing it

Imara un­veiled da­ta from two sub­groups of a Phase IIa tri­al for its lead com­pound Wednes­day, aim­ing to con­jure up a pos­i­tive light de­spite chal­lenges tied to the Covid-19 pan­dem­ic. But in­vestors weren’t buy­ing it and sent the com­pa­ny’s shares in­to a tail­spin.

The ex­per­i­men­tal drug, dubbed IMR-687, is be­ing eval­u­at­ed for sick­le cell dis­ease as both a monother­a­py and in com­bi­na­tion with hy­drox­yurea. In the monother­a­py sub­group, Imara re­port­ed IMR-687 showed no mean­ing­ful changes in F-cells, fe­tal he­mo­glo­bin (HbF) lev­els or Hb lev­els from base­line af­ter 24 weeks.

Ad­di­tion­al­ly, in the com­bo sub­group, the can­di­date demon­strat­ed nu­mer­i­cal in­creas­es in F-cells and HbF lev­els from base­line, but Hb lev­els did not mean­ing­ful­ly change. But Imara was un­able to mea­sure the dif­fer­ence against a place­bo in both groups, as pa­tients in those arms could not be eval­u­at­ed due “in part” to missed study vis­its, the com­pa­ny said.

Ul­ti­mate­ly, on­ly one place­bo pa­tient in the com­bi­na­tion group had ap­pro­pri­ate bio­mark­er da­ta af­ter the 24-week pe­ri­od, and p-val­ues were not re­port­ed. Imara at­tempt­ed to spin those less-than-stel­lar re­sults in­to a win in a re­lease, but in­vestors saw through the ef­fort im­me­di­ate­ly.

“I am en­cour­aged by the in­cre­men­tal da­ta from this read­out, es­pe­cial­ly in light of the COVID-19 pan­dem­ic chal­lenges,” lead in­ves­ti­ga­tor Biree An­de­mari­am said in a state­ment. “This in­cludes a fa­vor­able safe­ty pro­file of IMR-687, low­er rate of VOCs/SCPCs and VOC-re­lat­ed hos­pi­tal­iza­tions in the Pop­u­la­tion A1 monother­a­py arm and im­prove­ments in sev­er­al bio­mark­er re­sults across both the monother­a­py and com­bi­na­tion groups.”

Imara $IM­RA shares were down 33% in ear­ly trad­ing Wednes­day.

The re­sults make up part of a 93-pa­tient Phase IIa tri­al, study­ing four dif­fer­ent dose lev­els across the monother­a­py and com­bi­na­tion reg­i­mens. Wednes­day’s monother­a­py da­ta come from a reg­i­men of a once-dai­ly dose of 100 mg through 4 weeks, which es­ca­lates to 200 mg through an ad­di­tion­al 20 weeks.

In the com­bi­na­tion group, pa­tients took a 50 mg dose once a day on top of stan­dard of care HU, with es­ca­la­tion af­ter 4 weeks to 100 mg for the re­main­ing 20 weeks. There were 18 to­tal in­di­vid­u­als in this monother­a­py co­hort and 14 in the com­bo por­tion.

Imara can still hang its hat on in­ter­im da­ta from the oth­er sub­groups in the study, which showed the high­er dose of the monother­a­py had sta­tis­ti­cal­ly sig­nif­i­cant in­creas­es in F-cells, as well as a dose-de­pen­dent in­crease in HbF lev­els in adults. There was al­so a mean in­crease from base­line of 1.7% in HbF per­cent­age in the 100 mg / 200 mg dose group through week 24, a fig­ure that SVB Leerink an­a­lyst Joseph Schwartz had deemed promis­ing.

Ahead of Wednes­day’s da­ta, Schwartz had been hop­ing to see a fur­ther rise in this spe­cif­ic da­ta point, re­gard­less of whether or not it reached the 3% lev­el the FDA set as the thresh­old for the Phase IIb study that launched in Au­gust. But the over­all per­cent change in monother­a­py re­port­ed Wednes­day was -1.1%, even though Imara not­ed an ab­solute, dose-de­pen­dent in­crease in HbF of 1.3% when pa­tients es­ca­lat­ed from 100 mg to 200 mg.

Schwartz wrote Wednes­day that he does not be­lieve the da­ta is a good in­di­ca­tor of the up­com­ing Phase IIb re­sults, and still be­lieves the 3% fig­ure is achiev­able. He al­so not­ed that the dos­es be­ing used in that study are much high­er — up to 400 mg — than those in Phase IIa, with signs point­ing to longer and high­er dos­es re­sult­ing in bet­ter ef­fi­ca­cy.

IMR-687 was one of a group of small mol­e­cule PDE9 in­hibitors that Imara had li­censed from Lund­beck. The the­o­ry is that block­ing PDE9 in­creas­es cyclic GMP lev­els, which is as­so­ci­at­ed with re­ac­ti­va­tion of fe­tal he­mo­glo­bin and thus re­store some func­tion­al­i­ty im­paired in blood dis­or­ders. Imara went pub­lic in March fol­low­ing a $75.2 mil­lion IPO raise.

This ar­ti­cle has been up­dat­ed to in­clude SVB Leerink’s Joseph Schwartz’s most re­cent analy­sis, pub­lished late Wednes­day morn­ing.

Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Big week for Alzheimer’s da­ta; As­traZeneca buys cell ther­a­py start­up; Dig­i­tal ther­a­peu­tics hits a pay­er wall; and more

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Am­gen, years be­hind ri­vals, says PhI obe­si­ty drug shows dura­bil­i­ty signs

While NBC ran “The Biggest Loser” for 17 seasons, deemed toxic by critics for the reality show’s punishing exercise and diet upheavals, researchers in pharmaceutical labs have been attempting to create prescription drugs that induce weight loss — and one pharma betting it can require less frequent dosing is out with a new crop of data.

Amgen was relatively late to the game compared to its approved competitor Novo Nordisk and green light-approaching rival Eli Lilly. But early data suggested Amgen’s AMG 133 led to a 14.5% weight reduction in the first few months of dosing, buoying shares earlier this fall, and now the California pharma is out with its first batch of durability data showing that figure fell slightly to 11.2% about 150 days after the last dose. Amgen presented at the 20th World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease on Saturday afternoon.

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Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls

Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

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US month­ly costs for biosim­i­lars 'sub­stan­tial­ly high­er' than Ger­many or Switzer­land, JA­MA re­search finds

As the global biologics market is expected to hit nearly the half-trillion-dollar mark this year, new JAMA research points to the importance of timely biosimilar entry, particularly as fewer biosimilars are entering the US than in Europe, and as monthly treatment costs for biosimilars were “substantially higher” in the US compared with Germany and Switzerland.

Among the three countries, biosimilar market share at launch was highest in Germany, but increased at the fastest rate in the US, the authors from the University of Zurich’s Institute of Law wrote in JAMA Network Open today.

Kirk Myers is shown in a still image from a new film series showcasing the efforts of HIV advocates funded by Gilead.

Gilead spot­lights HIV projects and the com­mu­ni­ty lead­ers dri­ving them in new mi­ni-doc­u­men­tary films

Gilead is going behind the scenes of some of the HIV initiatives it funds through grants in a new film series narrated by the people helming the projects.

The first four films and leaders come from across the US — Arianna Lint in Florida and Puerto Rico, Cleve Jones in San Francisco, June Gipson in Mississippi and Kirk Myers in Texas. Their HIV-focused efforts range from addressing unmet needs of the transgender community to delivering social services and high-quality health care in underserved communities.

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EMA pulls an opi­oid from the 1950s used to treat dry cough

The European Medicines Agency said Friday that it’s pulling from all European markets pholcodine-containing medicines, which are an opioid used in adults and children for the treatment of dry cough and in combo with other drugs as a treatment for cold and flu.

The decision to pull the medicines comes as the EMA points to the results from the recent ALPHO study, which show that use of pholcodine during the 12 months preceding anesthesia is linked to a risk of an anaphylactic reaction related to the neuromuscular blocking agents (NMBAs) used (with an adjusted OR of 4.2, and a 95% confidence interval of 2.5 to 6.9).

David Arthur, Salarius Pharmaceuticals CEO

Salarius Phar­ma­ceu­ti­cals sees with­drawals, 3 of 13 pa­tient re­spon­ders in sar­co­ma tri­al

The Houston-based biotech Salarius Pharmaceuticals is lifting the cover on data from a Phase I/II trial for a drug currently on voluntary hold after a patient death, and the results appear to have underwhelmed investors.

Salarius’ candidate, dubbed seclidemstat, is an oral LSD1 inhibitor that is meant to treat Ewing sarcoma and FET-rearranged sarcomas in patients under 12 years old. The biotech had presented data with 13 patients with “first- and second-relapse Ewing sarcoma” who were treated in combination with topotecan and cyclophosphamide.