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.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

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