Pfizer Rare Disease Plans Back On Track With Resubmission of Tafamidis

Pfizer gained the therapy to treat a rare genetic neurologic disorder in its 2010 acquisition of folded protein company FoldRx.

Pfizer Inc.’s successful resubmission of the NDA for tafamidis, a novel therapy to treat a rare progressive neurodegenerative disease, puts the company back on track with its move into the orphan disease space.

The company announced Feb. 15 that FDA had accepted the resubmission and granted a priority review of the application, which now has a PDUFA date sometime in June.

FDA greeted the initial filing with a “refuse to file” letter (Also see "FDA Sends Back Filing For Pfizer's Tafamidis, Acquired in FoldRx Deal" - Pink Sheet, 4 Apr, 2011.). But Pfizer said it was required to do no additional trials and had the data on hand to fill in the blanks.

Pfizer had hoped for a quick path to approval for the drug as it builds its orphan disease program. Tafamidis treats transthyretin amyloid polyneuropathy, also known as familial amyloid polyneuropathy, an autosomal disorder that affects peripheral nerve tissue. It came to Pfizer though the 2010 acquisition of Cambridge, Mass.-biotech FoldRx Pharmaceuticals Inc., which has expertise in protein misfolding diseases (Also see "Pfizer Adds To Specialty Care Division With Purchase Of FoldRx" - Pink Sheet, 1 Sep, 2010.).

Tafamidis was approved in Nov. 2011 by regulators in Europe, where it is branded Vyndaquel. About 8,000 people worldwide are affected by TTR-FAP, according to Pfizer.

As part of its strategy for success in the post-blockbuster era, Pfizer announced in 2010 that it would create a dedicated Rare Disease Unit within its Specialty Care Business to develop and commercialize compounds such as tafamidis. Orphan and so-called ultra-orphan drugs aim for small patient populations and command a high price with little added sales and marketing expense. Such diseases are associated with knowledgeable patient support organizations and specialists that are familiar and involved in drug development, which can ease commercialization.

Pfizer said it has 17 medicines approved for orphan indications in the U.S. to treat diseases such as hemophilia, acromegaly, pulmonary arterial hypertension and rare cancers. Included in the count is a May 2011 approval of top-selling kidney cancer drug Sutent (sunitinib) to treat pancreatic neuro-endocrine tumors (Also see "Sutent Cleared For Pancreatic Tumors, But With Caveat On Efficacy" - Pink Sheet, 23 May, 2011.). But it also has the lung cancer therapy Xalkori (crizotinib), which targets a genetic mutation that affects only about 1% to 7% of non-small cell lung cancer patients (Also see "Pfizer’s Crizotinib Eases Past FDA With Targeted Population" - Pink Sheet, 29 Aug, 2011.).

Next Up: Uplyso

Tafamidis is the second of Pfizer’s orphan drugs to run into trouble with FDA. In February last year, FDA met the application for Gaucher disease drug Uplyso (taliglucerase alfa), on which Pfizer partners with Israeli biotech Protalix BioTherapeutics Inc., with a “complete response” letter asking for more data from a pair of registrational trials and information to complete the chemistry, manufacturing and controls portion of the filing (Also see "FDA Delays Approval Of Protalix/Pfizer Gaucher Drug; Seeks More Data From Late-Stage Trials" - Pink Sheet, 25 Feb, 2011.). They now have a May 1 action date on their response, which likely included critical results from a switching study.

Protalix, which uses plant cells to produce recombinant therapies without infringing patents on animal-cell based recombinants, engineered Uplyso to be interchangeable with Sanofi/Genzyme Corp.’s Cerezyme (imiglucerase), which for years has been the only option available for Gaucher patients. Shire PLC gained approval for its enzyme replacement product Vpriv (velaglucerase alfa) in February 2010. Both Cerezyme and Vpriv are produced in animal cells.

Furthering its interest in lysosomal storage disorders, Pfizer forged a strategic research collaboration in April 2011 with Zacharon Pharmaceuticals Inc., a San Diego start-up with a platform for developing small molecule drugs targeting carbohydrate polymers or glycans. Lysosomal storage diseases are a group of over 40 inherited disorders, among them Gaucher, Fabry, Pompe, mucopolysaccharidoses, all characterized by a deficiency in one or more enzymes that degrade glycans, leading to an accumulation of undigested glycan fragment in the lysosome and ultimately to progressive deterioration of the physical and/or mental state of the patient. Zacharon is a portfolio company of Avalon Ventures.

Projects In The Rare/Orphan Disease Pipeline

Pfizer’s pipeline shows a handful of therapies in late development to treat rare or orphan diseases, most of them attached to a licensing agreement.

Among them is an added indication for Xiaflex/Xiapex, approved in February 2010 to treat adult Dupuytren’s contracture with a palpable cord, a curling of the fingers toward the palm (Also see "Auxilium's Xiaflex Clears FDA With REMS To Educate Doctors On Safe Injection Techniques" - Pink Sheet, 3 Feb, 2010.). It is in Phase III studies for Peyronie’s disease, a curvature of the penis. Pfizer is partnered on the drug with Auxilium Pharmaceuticals Inc., in Malvern, Pa.

PF06460031 (GMI-1070) is in Phase II studies for vaso-occlusive crisis associated with sickle cell disease. Pfizer licensed the drug from GlycoMimetics Inc., in Gaithersburg, Md., in an exclusive deal announced Oct. 11, 2011 (Also see "Deals Of The Week: Pfizer/Humana, Teva/Par, Bayer/Yunona" - Pink Sheet, 17 Oct, 2011.).

And tofacitinib, developed in-house by Pfizer, is in Phase II studies for transplant rejection and dry eye (Also see "Tofacitinib Data Is In: As Effective As Humira, But Safety Remains A Question" - Pink Sheet, 12 Sep, 2011.). But the JAK inhibitor also is pending at FDA for more sizeable market – rheumatoid arthritis.