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.

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.”

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.

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.