(BGV) Catalysts: Health Agenda for the Week of Sept. 3
+------------------------------------------------------------------------------+
Catalysts: Health Agenda for the Week of Sept. 3
2012-09-03 12:37:40.243 GMT
By Andrew Berens, MD, Senior Biotech Analyst, Bloomberg Industries
Sept. 3 (Bloomberg Industries) -- Sept. 3-9 features two potential FDA decisions on New Drug Applications (NDAs).
Salix/Napo’s crofelemer has a Prescription Drug User Fee Act
(PDUFA) date for HIV-associated diarrhea on Sept. 5. Nuvo Research/Galderma’s resubmitted supplemental NDA for Pliaglis also has a PDUFA date estimated by Bloomberg Industries to be about Sept. 4. An FDA Anti-Infective Drugs Advisory Committee will discuss Novartis’s TOBI Podhaler NDA on Sept. 5. The European Respiratory Society (ERS) Annual Congress continues in Vienna through Sept. 5. See last week’s BI Key Events note for more details about important ERS presentations. Amicus will present data of its Pompe and Fabry disease drugs at the Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium on Sept. 5. ImmunoGen and Peregrine will present data of their lung cancer drugs at the Chicago Multidisciplinary Symposium in Thoracic Oncology Sept. 6-8.
Auxilium/Pfizer/BioSpecifics’s Xiaflex will have multiple-cords data presented at the American Society of Surgery of the Hand
(ASSH) annual meeting Sept. 6-8.
Key Factors:
Salix/Napo’s crofelemer has PDUFA for HIV-associated diarrhea
Salix/Napo’s crofelemer NDA for treatment of chronic diarrhea in people living with HIV/AIDS who are on anti retroviral therapy has a PDUFA date on Sept. 5. The NDA was submitted in December and received priority review by the FDA.
The original PDUFA date of June 5 was extended by three months in April as the FDA needed more time to complete a full review.
According to Salix, the FDA did not request additional studies.
Discovered by Napo, crofelemer is a novel, first-in-class compound for the condition, which, according to the Center for Disease Control (CDC), affects about 338,000 people out of the
1.2 million living with HIV/AIDS in the U.S.
Salix licensed the drug from Napo in December 2008, receiving exclusive license to the HIV-associated diarrhea indication and the additional indications of pediatric diarrhea and acute infectious diarrhea in North America, Europe and Japan, as well as a worldwide license to all other possible human indications. Napo sued Salix in May 2011, alleging that Salix failed to satisfy its contractual obligations to commercialize crofelemer in a timely manner. Napo notified Salix that it was terminating their collaboration agreement in November 2011 on the grounds that Salix breached the agreement.
Subsequently, Salix submitted the NDA in December, based on data from the Phase III trial ADVENT, which became available in November 2010. Napo was also involved in a dispute with Glenmark Pharmaceuticals over the collaboration agreement that granted Glenmark an exclusive license to distribute and commercialize crofelemer in 140 emerging countries including India. Recently the International Center for Dispute Resolution (ICDR) ruled in favor of Glenmark, rejecting Napo’s arbitration claim that Glenmark had materially breached the collaboration agreement by failing to commercialize the drug in all 140 countries in its territory. The ICDR also upheld Glenmark’s claim that it has the exclusive rights to distribute crofelemer through relief agencies in these countries.
Nuvo/Galderma’s sNDA for Pliaglis has estimated PDUFA
Nuvo Research/Galderma’s Pliaglis (lidocaine and tetracaine 7%/7% cream) resubmitted supplemental NDA for local dermal anesthesia on intact skin in adults prior to superficial dermatological procedures has a PDUFA date estimated by Bloomberg Industries to be about Sept. 4. Peelable from the skin when exposed to air, Pliaglis is a topical local anesthetic cream enabled by Nuvo’s proprietary Phase-Changing Topical Peel technology. It is designed to have faster onset of action and be easier to use than currently available options, according to Nuvo. There are no FDA-approved competitor products, Nuvo said recently, although the drug will compete with local anesthetics that can be both injectable or topical.
The worldwide marketing rights to Pliaglis were licensed to Galderma. Pliaglis was approved by the FDA in June 2006, and voluntarily removed from the U.S. market in 2008 due to manufacturing issues at Galderma’s third-party contract manufacturer. Galderma subsequently transferred Pliaglis production to its own facilities and resolved the issues. An sNDA seeking to re-introduce the drug to market was accepted for review by the FDA in February and had an April 16 PDUFA date.
The FDA issued a complete response letter (CRL) to the sNDA on the PDUFA date, and requested additional information related to the manufacturing transfer of Pliaglis from a third-party contract manufacturer to Galderma’s manufacturing facility, as well as additional stability data and proposed labeling revisions, without requiring require any new clinical or toxicology studies, according to the companies. Galderma resubmitted the sNDA on May 4 and expects a four-month review period by the FDA.
FDA panel reviews Novartis’s TOBI Podhaler Sept. 5
An FDA Anti-Infective Drugs Advisory Committee is scheduled to meet Sept. 5 to review Novartis’s NDA for TOBI Podhaler (tobramycin inhalation dry powder) for treatment of chronic Pseudomonas aeruginosa lung infections in cystic fibrosis patients aged 6 years and older. The NDA was submitted in December 2011 and is estimated by Bloomberg Industries to have a PDUFA date in October. The drug received EU approval in July 2011, after the CHMP issued a positive opinion in September 2010. Novartis markets TOBI, a solution form of tobramycin delivered via a nebulizer, in the U.S., EU, and other countries.
TOBI was first introduced in 1997. Currently there are two FDA- approved drugs for the management of Pseudomonas aeruginosa lung infections in cystic fibrosis patients: TOBI and Gilead’s Cayston, which is also a liquid formulation administered with a nebulizer. Novartis recorded $296 million in revenue for TOBI/tobramycin in 2011, while Gilead produced $77.5 million for Cayston.
Enabled by Novartis’s PulmoSphere technology, the dry powder formulation named TOBI Podhaler is intended to provide more convenient administration of the drug. It is administered with a portable and disposable device called T-326 and does not require refrigeration of the active compound or a power source for the delivery device. In clinical trials, TOBI Podhaler was shown to have cut administration time by 72% compared with TOBI.
Recently Bayer initiated global Phase III trials of its drug- device combination Ciprofloxacin Dry Powder for Inhalation in patients with non-cystic fibrosis bronchiectasis (NCFB) that also uses Novartis’s PulmoSphere technology and T-326 inhaler.
The FDA released the briefing document for the panel on Aug. 31. The document noted high drop-out rate in one of the two double-blind, placebo-controlled pivotal studies, Study C2301, which had the primary analysis conducted on 59% of the original intent-to-treat population, and said this limitation could introduce potential biases. It also raised questions about the sustainability of the treatment effect. The other double-blind, placebo-controlled pivotal study, Study C2303, did not accrue the projected sample size and failed to meet its primary endpoint. The briefing document also said that in the open-label Study C2302, which compared TOBI Podhaler with TOBI, there were a larger percentage of discontinuations in the TOBI Podhaler arm (26.9% vs. 18.2%), with a greater proportion of discontinuations attributed to adverse events (14% vs. 8.1%). In addition, 51.0% of patients in the TOBI Podhaler arm had treatment-related adverse events, compared with 20.1% in the TOBI arm. There were three deaths in the TOBI Podhaler arm vs. none in the TOBI arm, with two of the deaths attributable to pulmonary exacerbations.
The FDA is also concerned about the occurrence of reduced susceptibility of Pseudomonas aeruginosa to tobramycin while on TOBI Podhaler compared with TOBI, and the consequences this may have on the treatment outcome for the patient.
The document noted that in Study C2302, patients on TOBI Podhaler had slightly worse compliance scores compared with those on TOBI, even though TOBI Podhaler was supposed to be easier to use. This study reported statistically higher patient satisfaction assessed by questionnaires for TOBI Podhaler, while the FDA cautioned that it can be difficult to draw a relationship between treatment satisfaction and clinical results.
Amicus presents data of AT2220 for Pompe, migalastat for Fabry
The Society for the Study of Inborn Errors of Metabolism
(SSIEM) Annual Symposium takes place in Birmingham, U.K. on Sept. 4-7. Amicus will present AT2220 (duvoglustat) preliminary data from Phase II drug-drug interaction study (Study 010) in co-administration with enzyme replacement therapy (ERT) for Pompe disease, as well as preclinical data of direct co- formulation with an ERT, on Sept. 5. The company reported top- line preliminary results of the first two lower dose cohorts of the ongoing study in June. A third cohort of higher dose was fully enrolled as of June and the highest dose cohort, Cohort 4, is expected to become fully enrolled in 3Q. Amicus plans to present full data from all four cohorts and provide an update on further development plan of this agent for Pompe disease in 4Q.
Lumizyme (Myozyme, alglucosidase alfa) is an ERT marketed by Sanofi for Pompe disease and the only approved drug for the disease.
Also presented on Sept. 5 will be screening results from the Phase III Study 011 (FACETS) of monotherapy of Amicus/GlaxoSmithKline’s Amigal (migalastat HCl) in Fabry disease. Both AT2220 and Amigal are oral pharmacological chaperones based on Amicus’s proprietary technology, intended to become an alternative to ERT or stabilize and enhance ERT products.
Amigal is being developed for Fabry disease in two Phase III monotherapy trials: Study 011 vs. placebo for U.S.
registration under the accelerated approval pathway, and Study
012 vs. ERT for global registration and to convert the U.S.
accelerated approval to a full approval. Study 011 is fully enrolled, with six-month and 12-month data to be released in 4Q.
Study 012 is expected to become fully enrolled by year-end. The companies also plan to present full data from the Phase II drug- drug interaction Study 013 in co-administration with ERT for Fabry disease in 4Q. Preliminary data from the trial were presented at the Lysosomal Disease Network WORLD Symposium in February. Recently Amicus and GlaxoSmithKline expanded their collaboration for Fabry disease and plan to initiate Phase I trials of Amigal co-formulated with GlaxoSmithKline/JCR’s proprietary ERT JR-051 next year. Amicus will market all future Fabry products in the U.S., while GlaxoSmithKline will commercialize them in the rest of world.
Marketed ERT therapies for Fabry disease include Sanofi’s Fabrazyme, which is marketed globally, and Shire’s Replagal, marketed in the EU and other countries. Shire withdrew Replagal’s U.S. application in March, due to likely requirement by the FDA for additional controlled trials. Supply of Fabrazyme has been unable to meet demand following manufacturing constraints due to contamination issues in Genzyme’s (now part of Sanofi) Allston Landing facilities in 2009. In January Genzyme received regulatory approvals from the FDA and the EMA of its new Framingham manufacturing facility and began shipping products produced in the new plant in March. The company has the goal of completely returning to normal supply levels globally starting in 2Q.
ImmunoGen, Peregrine present data: IMGN901, bavituximab
The Chicago Multidisciplinary Symposium in Thoracic Oncology will take place on Sept. 6-8.
-- ImmunoGen will present IMGN901 (lorvotuzumab mertansine) Phase I dose-finding data in first-line small-cell lung cancer
(SCLC) and other tumor types at the conference. Wholly owned by ImmunoGen, IMGN901 is an antibody-drug conjugate consisting of the Company’s CD56-targeting antibody and its proprietary cytotoxic agent DM1 attached via one of ImmunoGen’s engineered linkers. IMGN901 entered Phase II testing for first-line SCLC earlier this year: the NORTH trial is expected to have an interim analysis and initial data in 2H13. Pivotal trials in this setting might be initiated in 2014. IMGN901 has orphan drug designation for SCLC in the U.S. and in Europe.
ImmunoGen’s most advanced antibody-drug conjugate is trastuzumab emtansine (T-DM1), developed in partnership with Roche. The companies announced on Aug. 27 that the overall survival (OS) co-primary endpoint was met in the Phase III EMILIA trial in second-line HER2-positive second-line metastatic breast cancer and that Roche has recently submitted a Biologics License Application (BLA) for the drug, with an EU application to be submitted shortly. If the FDA accepts the BLA for review, a decision that could come in the next two months, the PDUFA date is estimated by Bloomberg Industries to be about June 26, 2013, assuming standard review. Earlier this year the companies reported the trial’s progression-free survival (PFS) co-primary endpoint was met and presented the data at the American Society of Clinical Oncology (ASCO) annual meeting in June.
-- Peregrine will also present bavituximab data from the Phase IIb trial in combination with docetaxel in second-line non-small cell lung cancer (NSCLC) on Sept. 7. Top-line data on overall response rates and PFS were reported in May, and at the presentation the company will provide an update on median OS, anticipated to become available in 2H. The median OS had not been reached in the two bavituximab-containing arms as of Aug.
15, according to the company. Second-line NSCLC is the first indication Peregrine is pursuing for bavituximab, with pivotal Phase III trial expected to initiate by mid-2013. It anticipates an End-of-Phase II meeting with the FDA by year-end to discuss design of the Phase III program. Peregrine recently said it has received “a surge in partnering discussions” including “major players in oncology” following release of the top-line data in May. The company intends to retain a significant part of the U.S. rights and will focus on partnering for outside-of-U.S.
markets, with a goal of securing a partner prior to initiation of Phase III trial.
Bavituximab is a phosphatidylserine targeting antibody and the company’s lead compound. Peregrine is also expecting by year-end median OS data from a Phase II trial of bavituximab in combination with paclitaxel and carboplatin in front-line NSCLC, as well as interim OS data from a Phase II trial in combination with gemcitabine in previously untreated stage IV pancreatic cancer. PFS data from the front-line NSCLC trial was reported in March.
Auxilium/Pfizer/BioSpecifics’ Xiaflex multicord data presented
At the American Society of Surgery of the Hand (ASSH) Annual Meeting in Chicago on Sept. 6-8, Auxilium/Pfizer/BioSpecifics’s Xiaflex (Xiapex, collagenase clostridium histolyticum injection) will have data presented from a Phase IIIb trial of multiple concurrent injections in 60 Dupuytren’s contracture patients with multiple palpable cords.
Top-line results were reported in July. Currently Xiaflex is approved for treatment of Dupuytren’s contracture patients with a palpable cord. Auxilium plans to initiate a larger trial for concurrent treatment of multiple palpable cords in 3Q, with data expected in 1H14 and regulatory filing planned for 2H14 to expand the drug’s label to this additional use. Pfizer markets the drug in Europe under the brand Xiapex. Actelion has development and commercial rights for it in Canada, Australia, Brazil and Mexico. Xiaflex recently received approval in Canada and is expected to be introduced to the Canadian market in 1H13.
Asahi Kasei has development and commercial rights in Japan.
Xiaflex is also in late-stage development for Peyronie’s disease. Auxilium released top-line data of the Phase III IMPRESS trials in Peyronie’s disease in June and plans to submit an sBLA for this new indication by year-end. At the Sexual Medicines Society of North America (SMSNA)/International Society for Sexual Medicine (ISSM) Joint Annual Meeting in Chicago on Aug. 26-30, Auxilium presented a baseline analysis from the IMPRESS program focusing on the psychosocial impact on men with Peyronie’s disease, as well as photographs and data from a subset of IMPRESS patients in an open-label sub-study using 3-D photographic technology for 360 degree assessment of penile curvature deformity, the first such study conducted. The company plans to publish detailed data of the IMPRESS trials, including the primary and second endpoints, in a peer-reviewed medical journal.
Last updated Aug. 31, 2012
With assistance from the Bloomberg Industries team including Grace Guo in New York.
--Editor: Doug Zehr
To contact the analyst on this story: Andrew Berens in New York at +1-609 279-5462 or aberens@bloomberg.net
#<644414.8033026.3.0.2.9.2497>#
-0- Sep/03/2012 12:37 GMT
AI
