Af­ter roller-coast­er week, CRL forces a reck­on­ing on Or­p­hazyme in­vestors — in­flat­ed shares plum­met

The meme stock par­ty is over for Or­p­hazyme.

Af­ter a week of fren­zied trad­ing — where its shares sky­rock­et­ed, at one point, more than 1000% for no ap­par­ent rea­son — the Copen­hagen-based biotech dis­closed ear­ly Fri­day that the FDA has re­ject­ed its lead drug as a treat­ment for Nie­mann-Pick dis­ease type C, ask­ing for more da­ta.

Shares $ORPH plum­met­ed 56.39% to $6.35 — and it will like­ly face an up­hill bat­tle find­ing its way back up.

Or­p­hazyme had to push past a Phase II/III fail­ure to file ari­mo­clo­mol with reg­u­la­tors. While the mol­e­cule — which they call a heat shock pro­tein am­pli­fi­er — had missed the pri­ma­ry end­points, ex­ecs high­light­ed some pos­i­tive sub­group analy­sis.

But it was clear­ly far from enough to cut it at the FDA.

Both of those pri­ma­ry end­points in­volved rat­ing scales: One is a dis­ease-spe­cif­ic mea­sure dubbed the NPC Clin­i­cal Sever­i­ty Scale, while the oth­er was a self-rat­ing tool known as Clin­i­cal Glob­al Im­pres­sion of Im­prove­ment. Ac­cord­ing to the com­pa­ny, reg­u­la­tors took se­ri­ous is­sue with the for­mer.

The FDA is­sued the CRL based on need­ing ad­di­tion­al qual­i­ta­tive and quan­ti­ta­tive ev­i­dence to fur­ther sub­stan­ti­ate the va­lid­i­ty and in­ter­pre­ta­tion of the 5-do­main NPC Clin­i­cal Sever­i­ty Scale (NPCC­SS) and, in par­tic­u­lar, the swal­low do­main. Fur­ther, the FDA not­ed in the CRL that ad­di­tion­al da­ta are need­ed to bol­ster con­fir­ma­to­ry ev­i­dence be­yond the sin­gle phase 2/3 clin­i­cal tri­al to sup­port the ben­e­fit-risk as­sess­ment of the NDA.

Christophe Bour­don

While ex­plor­ing the “po­ten­tial path for­ward,” CEO Christophe Bour­don says they will now fo­cus on pur­su­ing an EMA ap­proval, which would come ear­ly next year if a com­mit­tee with­in the Eu­ro­pean agency gives its thumbs up in Q4.

“In the short-term, we will need to re­duce our costs sub­stan­tial­ly and freeze all com­pa­ny ef­forts not re­lat­ed to clin­i­cal and reg­u­la­to­ry ac­tiv­i­ties to sup­port ap­proval for NPC,” he added.

NPC, which is char­ac­ter­ized by an in­abil­i­ty to trans­port cho­les­terol and oth­er lipids in and out of cells, is not the on­ly se­ri­ous dis­ease that Or­p­hazyme had been go­ing af­ter. But their luck was not any bet­ter in those oth­er ar­eas, as ari­mo­clo­mol has flunked piv­otal tri­als in the rare mus­cle-wast­ing dis­ease in­clu­sion body myosi­tis as well as amy­otroph­ic lat­er­al scle­ro­sis, leav­ing a shad­ow on its “pipeline in a prod­uct” dream.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

When ef­fi­ca­cy is bor­der­line: FDA needs to get more con­sis­tent on close-call drug ap­provals, agency-fund­ed re­search finds

In the exceedingly rare instances in which clinical efficacy is the only barrier to a new drug’s approval, new FDA-funded research from FDA and Stanford found that the agency does not have a consistent standard for defining “substantial evidence” when flexible criteria are used for an approval.

The research comes as the FDA is at a crossroads with its expedited-review pathways. The accelerated approval pathway is under fire as the agency recently signed off on a controversial new Alzheimer’s drug, with little precedent to explain its decision. Meanwhile, top officials like Rick Pazdur have called for a major push to simplify and clarify all of the various expedited pathways, which have grown to be must-haves for sponsors of nearly every newly approved drug.

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Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.

Take­da snaps up the Japan­ese rights to an old Shire cast-off; Boehringer In­gel­heim ac­quires Abexxa Bi­o­log­ics

A week before the FDA is set to decide on Mirum Pharmaceuticals’ lead liver disease drug — an old Shire cast-off called maralixibat — Takeda is swooping in to secure the rights in Japan.

Maralixibat’s roots trace back to Lumena, which was snapped up by Shire for $260 million-plus back in 2014. While the candidate had failed mid-stage studies at Shire, Mirum believes better trial design and patient selection will deliver the wins it needs. The drug is currently in development for Alagille syndrome (a condition called ALGS in which bile builds up in the liver), progressive familial intrahepatic cholestasis (PFIC, which causes progressive liver disease) and biliary atresia (a blockage in the ducts that carry bile from the liver to the gallbladder).

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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Jay Bradner (Jeff Rumans for Endpoints News)

Div­ing deep­er in­to in­her­it­ed reti­nal dis­or­ders, No­var­tis gob­bles up an­oth­er bite-sized op­to­ge­net­ics biotech

Right about a year ago, a Novartis team led by Jay Bradner and Cynthia Grosskreutz at NIBR swooped in to scoop up a Cambridge, MA-based opthalmology gene therapy company called Vedere. Their focus was on a specific market niche: inherited retinal dystrophies that include a wide range of genetic retinal disorders marked by the loss of photoreceptor cells and progressive vision loss.

But that was just the first deal that whet their appetite.

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