New Inhaled Insulin, Provenge, Top List of 2010 Action Dates
By Jennifer Boggs
Assistant Managing Editor
Though 2009 has passed (finally), the year saw a number of regulatory filings - Danbury, Conn.-based Biodel Inc.'s new drug application for Viaject injectable insulin made it just under the wire with a Dec. 30 submission - that make for some much-awaited action dates in the first half of 2010.
Coming up Jan. 16 is the PDUFA date for MannKind Corp.'s Afresa, a new inhaled insulin product that proved noninferiority to insulin, as well as a lower risk of hypoglycemia, in Phase III studies. Valencia, Calif.-based MannKind also has plans for a smaller, next-generation inhaler device, likely to go before regulators later in 2010.
While a first-pass approval is not certain, the company's biggest challenge will be on the sales end, as it attempts to overcome lingering doubts left over from Pfizer Inc.'s failure with Exubera and early termination of other similar programs. Though Afresa, with its more convenient inhaler, is believed to be a better product, "physicians may be skeptical of inhaled insulins in light of the Exubera experience," wrote Leerink Swann analyst Joseph Schimmer.
MannKind also hopes to secure a partnership upon approval. The firm originally had set an end-of-2009 goal for a deal, but, after a potential suitor was unable to continue negotiations, decided to wait until the label for Afresa is clarified. (See BioWorld Today, Oct. 5, 2009.)
Elsewhere in the diabetes space, glucagon-like peptide-1 drugs are on the FDA's agenda early this year. Bagsvaerd, Denmark-based Novo Nordisk AS is expecting agency feedback shortly on liraglutide, a once-daily treatment for Type II diabetes, though a mixed advisory panel vote in April raised concerns based on preclinical data showing thyroid tumors in rodents. (See BioWorld Today, April 6, 2009.)
There's also the small chance that those concerns might cast a pall over the entire GLP-1 class, putting in jeopardy the chance of a once-weekly version of Byetta (exenatide) gaining approval by its March 5 PDUFA date, though that drug's developers - Amylin Pharmaceuticals Inc., Eli Lilly and Co. and Alkermes Inc. - have pointed out that preclinical studies of exenatide LAR have shown no similar tumor risks.
Fampridine up for Review in MS
</B>Investors of Acorda Therapeutics Inc. - and Biogen Idec Inc., which paid $110 million up front in a July partnering deal - are eagerly awaiting Fampridine-SR's Jan. 22 action date.
Despite concerns raised in October briefing documents, the FDA's Peripheral and Central Nervous System Drugs Advisory Panel voted in Fampridine's favor, stating that the Phase III data showed that the potassium channel blocker effectively improved the walking ability in patients with multiple sclerosis. (See BioWorld Today, Oct. 15, 2009.)
Fampridine got unexpected priority review status from the FDA, but following that advisory meeting, Hawthorne, N.Y.-based Acorda submitted additional information for its proposed risk evaluation and mitigation strategy program, pushing its PDUFA data from October to January.
If approved, Fampridine would be the first product aimed specifically at improving walking ability in MS patients. Commercial success, however, depends heavily on the drug's label and REMS wording, particularly in regard to nonresponders.
According to Leerink's Schimmer, consultants have noted that it would be difficult to design a REMS that restricts use only to responders, and "even patients who are not considered responders by the Timed 25 Foot Walk Test still achieve a difficult-to-quantify benefit from [the] drug."
Will Provenge Prove Worthy?
</B>One of this year's most anticipated approvals has to be Dendreon Corp.'s prostate cancer vaccine Provenge (sipuleucel-T), which has a May 1 PDUFA date.
The Seattle-based firm has been on a roller coaster ride since getting a complete response letter in 2007. Since then, the company completed a Phase III trial showing that Provenge reduced the overall risk of death by 22.5 percent compared to placebo and submitted a new biologics license application for use of the drug in men with metastatic castrate-resistant prostate cancer. (See BioWorld Today, April 29, 2009.)
Assuming its approval by May 1, analysts have estimated 2010 sales of Provenge to fall between $50 million and $70 million.
Dendreon has been raising serious money in the last part of 2009, most recently adding $356 million in a stock offering, though approval of Provenge could position the firm for a lucrative partnership or even an outright acquisition. (See BioWorld Today, Dec. 14, 2009.)
Other oncology drugs set for review this year include Tarceva (erlotinib) from OSI Pharmaceuticals Inc. and Genentech Inc. (now part of Roche), which has a Jan. 18 PDUFA date for a supplemental NDA as a first-line maintenance treatment in non-small-cell lung cancer patients based on the Phase III SATURN date.
Seattle-based Cell Therapeutics Inc.'s anthracycline drug pixantrone has an action date of April 23, though an advisory panel is slated to meet Feb. 10 to review the drug's use in relapsed or refractory aggressive non-Hodgkin's lymphoma. That same panel also is expected to review Melbourne, Australia-based ChemGenex Pharmaceuticals Ltd.'s Omapro (omacetaxine mepesuccinate) in adults with chronic leukemia who have failed prior therapy with Gleevec (imatinib, Novartis AG) and who have developed the Bcr-Abl T315I mutation.
And A.P. Pharma Inc., of Redwood City, Calif., has a March 18 PDUFA date for APF530, a long-acting formulation of granisetron, in chemotherapy-induced nausea and vomiting.
ERT Competition Coming for Genzyme
</B>This year will no doubt be an important one for Genzyme Corp. Not only is the Cambridge, Mass.-based biotech planning to submit an application for its 4,000L Lumizyme (alglucosidase alfa) product - skipping the 2,000L approval that has been stymied by manufacturing troubles at its Allston Landing plant, but it's enzyme replacement therapy business is expected to face some tough competitors.
Shire plc, of Basingstoke, UK, expects an FDA decision on its Gaucher's disease drug velaglucerase by Feb. 28, though that drug has been available to patients on an emergency basis to make up for any shortfall of Genzyme's Cerezyme (imiglucerase) caused by the six-month shutdown of Allston.
Another Gaucher ERT from Carmiel, Israel-based Protalix BioTherapeutics Inc. is finishing up a rolling biologics application and its approval is anticipated to follow shortly after velaglucerase. Protalix's drug, Uplyso (taliglucerase alfa), would be the first approved ERT manufactured in a plant cell-based system.
Genzyme's Fabry disease franchise also faces a threat from Shire, which filed a BLA for Replagal (agalsidase alfa), another drug available under an early access program thanks to the Allston debacle. The Replagal application was filed last month, and Shire anticipates priority review.
Drugs for Restless Legs, Jet Lag and More
</B>On the FDA's February agenda is a NDA for Solzira (gabapentin enacarbil), Santa Clara, Calif.-based XenoPort Inc.'s drug for restless legs syndrome, set for review by Feb. 9. The drug, which met its endpoint in three Phase III trials, is partnered with London-based GlaxoSmithKline plc, and XenoPort exercised its co-promotion option earlier this year. (See BioWorld Today, April 14, 2009.)
Regulators are expected to make a decision by Feb. 13 on Foster City, Calif.-based Gilead Sciences Inc.'s cystic fibrosis drug aztreonam. An advisory panel last month backed the drug, an aerosolized form of aztreonam lysine, as a therapy to improve respiratory symptoms and pulmonary functions in CF patients infected with Pseudomonas aeruginosa. (See BioWorld Today, Dec. 11, 2009.)
Cephalon Inc., of Frazer, Pa., anticipates a decision by March 29 for its sNDA for Nuvigil (armodafinil) in jet lag, specifically to improve wakefulness in patients with excessive sleepiness associated with jet lag disorder due to eastbound travel. The PDUFA date was extended by three months from Dec. 29.
Later in 2010, PDUFA dates are set for naproxcinod (July 24), from NicOx SA, of Sophia Antipolis, France, for treating signs and symptoms of osteoarthritis, and for pirfenidone, an idiopathic pulmonary fibrosis drug from InterMune Inc., of Brisbane, Calif., which is expected to go before an advisory panel in the first half of this year.
Investors also are expecting the final approval of Amgen Inc.'s denosumab in osteoporosis this year. The drug, to be sold as Prolia, received a complete response letter in October, with the FDA seeking additional postmarketing details. (See BioWorld Today, Oct. 20, 2009.)
Published January 4, 2010