Cat­a­lyst Phar­ma's Fir­dapse bet on con­gen­i­tal myas­thenic syn­dromes turns sour

Months af­ter Fir­dapse mak­er Cat­a­lyst Phar­ma­ceu­ti­cals filed a law­suit against the FDA, the Flori­da com­pa­ny on Wednes­day said the drug had failed a piv­otal tri­al in pa­tients af­flict­ed with con­gen­i­tal myas­thenic syn­dromes (CMS), an um­brel­la term for rare neu­ro­mus­cu­lar dis­or­ders com­pris­ing a spec­trum of more than 50 ge­net­ic de­fects.

The drug, known chem­i­cal­ly as am­i­fam­pri­dine, was sanc­tioned for use in adult Lam­bert-Eaton myas­thenic syn­drome (LEMS) pa­tients in No­vem­ber 2018. The com­pa­ny is work­ing on ex­pand­ing the la­bel to in­clude pa­tients with CMS, MuSK-pos­i­tive myas­the­nia gravis (MuSK-MG) and spinal mus­cu­lar at­ro­phy (SMA).

Cat­a­lyst es­ti­mates that there are be­tween 1,000 and 1,500 CMS pa­tients in the Unit­ed States — there are at least 600 fam­i­lies with af­fect­ed in­di­vid­u­als who have been rep­re­sent­ed in sci­en­tif­ic lit­er­a­ture, ac­cord­ing to the NIH. Pa­tients with CMS car­ry mu­ta­tions in genes en­cod­ing pro­teins es­sen­tial for neu­ro­mus­cu­lar trans­mis­sion.

Cat­a­lyst’s late-stage study test­ed the drug against a place­bo in ge­net­i­cal­ly con­firmed CMS pa­tients. 20 pa­tients aged two and above were en­rolled in the tri­al, and 16 were ran­dom­ized. The drug failed to meet the main goal of sub­ject glob­al im­pres­sion (SGI) scale, a mea­sure used by clin­i­cians to rate the sever­i­ty of the ill­ness at the time of as­sess­ment, rel­a­tive to the clin­i­cian’s past ex­pe­ri­ence with pa­tients with the same di­ag­no­sis.

The com­pa­ny’s shares $CPRX slipped about 12.3% to $5 in pre­mar­ket trad­ing.

The sec­ondary end­point of mus­cle func­tion mea­sure (MFM) across all test­ed sub­types was al­so not met, al­though in­di­vid­ual pa­tient im­prove­ments were ob­served in some pa­tient sub-groups, the com­pa­ny said.

“Due to the small pa­tient preva­lence, the low num­ber of pa­tients test­ed, and het­ero­gene­ity of the dis­ease with a wide range of vari­a­tion in clin­i­cal pre­sen­ta­tion across its more than 50 sub­types, it was chal­leng­ing to demon­strate a sta­tis­ti­cal­ly sig­nif­i­cant ben­e­fit across mul­ti­ple sub­types,” Steven Miller, Cat­a­lyst’s COO and CSO said in a state­ment.

The com­pa­ny will meet the FDA be­fore the end of 2019 to fig­ure out the next steps for the CMA pro­gram. Mean­while, the Cat­a­lyst ex­pects to re­port da­ta from the MuSK-MG tri­al as well as re­sults from its SMA proof of con­cept study in the first half of next year.

Hav­ing launched in Jan­u­ary, Fir­dapse gen­er­at­ed about $41.3 mil­lion in sales in the first half of this year. Be­fore the drug (which car­ries an av­er­age an­nu­al list price of $375,000) was ap­proved by the FDA, hun­dreds of pa­tients had been able to ac­cess a sim­i­lar drug from com­pound­ing phar­ma­cies for a frac­tion of the cost, or Ja­cobus’ for free, as part of an FDA-rat­i­fied com­pas­sion­ate use pro­gram.

But the ap­proval of the Cat­a­lyst drug — ac­com­pa­nied by mar­ket ex­clu­siv­i­ty span­ning sev­en years — ef­fec­tive­ly pre­clud­ed Ja­cobus and com­pound­ing phar­ma­cies from sell­ing their ver­sions.

Then, in an un­ex­pect­ed twist, the FDA en­dorsed New Jer­sey-based Ja­cobus’ ver­sion in pe­di­atric pa­tients, on the ba­sis of adult da­ta — a move that could spark off-la­bel pre­scrip­tion in adults (As far as the FDA is con­cerned, doc­tors can pre­scribe drugs for off-la­bel use when they judge that it is med­ical­ly ap­pro­pri­ate for their pa­tient). Adding fu­el to the fire, Ja­cobus’s drug, Ruzur­gi, car­ries a list price that is less than half of Fir­dapse’s. Cat­a­lyst main­tains that typ­i­cal­ly, cov­ered pa­tients pay less than $10 per month out-of-pock­et.

In an in­ter­view with End­points News ahead of Cat­a­lyst’s third-quar­ter re­sults ex­pect­ed mid-No­vem­ber, chief Patrick McE­nany said that the Ruzur­gi ap­proval has trig­gered a “trick­le of ero­sion” on its LEMS pa­tient base. “It was not un­ex­pect­ed,” he said.

In June, Cat­a­lyst filed a law­suit against the health reg­u­la­tor — ef­fec­tive­ly ac­cus­ing the agency of bow­ing to po­lit­i­cal pres­sure sur­round­ing sky­rock­et­ing drug prices. Un­der fed­er­al law, the agency is meant to treat all com­pa­nies in the same man­ner. Cat­a­lyst has as­sert­ed the agency un­der­mined its or­phan drug ex­clu­siv­i­ty, and vi­o­lat­ed fed­er­al law by play­ing fa­vorites in the con­text of a hy­per­vig­i­lant pric­ing en­vi­ron­ment.

Tesla and SpaceX founder Elon Musk gestures to the audience after being recognized by President Trump following the successful launch of a Falcon 9 rocket at the Kennedy Space Center. (via Getty Images)

Tes­la chief Elon Musk teams up with Covid-19 play­er Cure­Vac to build 'R­NA mi­cro­fac­to­ries'

Elon Musk has joined the global tech crusade now underway to revolutionize vaccine manufacturing — now aimed at delivering billions of doses of a new mRNA vaccine to fight Covid-19. And he’s cutting right to the front.

In a late-night tweet Wednesday, the Tesla chief announced:

Tesla, as a side project, is building RNA microfactories for CureVac & possibly others.

That’s not a lot to go on. But the tweet comes a year after Tesla’s German division in Grohmann and CureVac filed a patent on a “bioreactor for RNA in vitro transcription, a method for RNA in vitro transcription, a module for transcribing DNA into RNA and an automated apparatus for RNA manufacturing.” CureVac, in the meantime, has discussed a variety of plans to build microfactories that can speed up the whole process for a global supply chain.

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Elias Zerhouni (Photo by Vincent Isore/IP3/Getty Images)

Elias Zer­houni dis­cuss­es ‘am­a­teur hour’ in DC, the de­struc­tion of in­fec­tious dis­ease R&D and how we need to prep for the next time

Elias Zerhouni favors blunt talk, and in a recent discussion with NPR, the ex-Sanofi R&D and ex-NIH chief had some tough points to make regarding the pandemic response.

Rather than interpret them, I thought it would be best to provide snippets straight from the interview.

On the Trump administration response:

It was basically amateur hour. There is no central concept of operations for preparedness, for pandemics, period. This administration doesn’t want to or has no concept of what it takes to protect the American people and the world because it is codependent. You can’t close your borders and say, “OK, we’re going to be safe.” You’re not going to be able to do that in this world. So it’s a lack of vision, basically just a lack of understanding, of what it takes to protect the American people.

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Sec­ond death trig­gers hold on Astel­las' $3B gene ther­a­py biotech's lead pro­gram, rais­ing fresh con­cerns about AAV

Seven months after Astellas shelled out $3 billion to acquire the gene therapy player Audentes, the biotech company’s lead program has been put on hold following the death of 2 patients taking a high dose of their treatment. And there was another serious adverse event recorded in the study as well, with a total of 3 “older” patients in the study affected.

The incidents are derailing plans to file for a near-term approval, which had been expected right about now.

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George Yancopoulos (Regeneron)

UP­DAT­ED: Re­gen­eron co-founder George Yan­copou­los of­fers a com­bat­ive de­fense of the po­lice at a high school com­mence­ment. It didn’t go well

Typically, the commencement speech at Yorktown Central School District in Westchester — like most high schools — is an opportunity to encourage students to face the future with confidence and hope. Regeneron president and co-founder George Yancopoulos, though, went a different route.

In a fiery speech, the outspoken billionaire defended the police against the “prejudice and bias against law enforcement” that has erupted around the country in street protests from coast to coast. And for many who attended the commencement, Yancopoulos struck the wrong note at the wrong time, especially when he combatively challenged someone for interrupting his speech with a honk for “another act of cowardness.”

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An ex­pe­ri­enced biotech is stitched to­geth­er from transpa­cif­ic parts, with 265 staffers and a fo­cus on ‘new bi­ol­o­gy’

Over the past few years, different teams at a pair of US-based biotechs and in labs in Japan have labored to piece together a group of cancer drug programs, sharing a single corporate umbrella with research colleagues in Japan. But now their far-flung operations have been knit together into a single unit, creating a pipeline with 10 cancer drug development programs — going from early-stage right into Phase III — and a host of discovery projects managed by a collective staff of some 265 people.

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Pfiz­er shares surge on pos­i­tive im­pact of their mR­NA Covid-19 vac­cine — part­nered with BioN­Tech — in an ear­ly-stage study

Pfizer and their partners at the mRNA specialist BioNTech have published the first glimpse of biomarker data from an early-stage study spotlighting the “robust immunogenicity” triggered by their Covid-19 vaccine, which is one of the leaders in the race to vanquish the global pandemic.

Researchers selected 45 healthy volunteers 18-55 years of age for the study. They were randomized to receive 2 doses, separated by 21 days, of 10 µg, 30 µg, or 100 µg of BNT162b1, “a lipid nanoparticle-formulated, nucleoside-modified, mRNA vaccine that encodes trimerized SARS-CoV-2 spike glycoprotein RBD.” Their responses were compared against the effect of a natural, presumably protective defense offered by a regular infection.

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New stan­dard of care? FDA hands Pfiz­er, Mer­ck KGaA an OK for Baven­cio in blad­der can­cer

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.”

Joseph Kim, Inovio CEO (Andrew Harnik, AP Images)

Pos­i­tive Covid-19 vac­cine da­ta? New mouse study? OWS in­clu­sion? Yep, but some­how, the usu­al tid­bits from In­ovio back­fire

You don’t go more than 40 years in biotech without ever getting a product to market unless you can learn the art of writing a promotional press release. And Inovio captures the prize in baiting the hook.

Tuesday morning Inovio, which has been struggling to get its Covid-19 vaccine lined up for mass manufacturing, put out a release that touched on virtually every hot button in pandemic PR.

There was, first and foremost, an interim snapshot of efficacy from their Phase I program for INO-4800.

On a roll, Mer­ck blazes through a new seg­ment of the bio­mark­er trail

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.