In the cardiovascular area, further data for two products with new approaches are expected.
Acorda Therapeutics Inc. is set to release Phase III data for twice-daily Ampyra (dalfampridine) Extended Release (ER) tablets in ischemic stroke. The company is exploring its potential to improve walking in people who are suffering from post-stroke walking difficulties (PSWD) after experiencing an ischemic stroke, based on encouraging proof-of-concept results in 2013. The product has been approved since 2010 for improving walking in patients with multiple sclerosis.
The Phase III MILESTONE trial tested two twice-daily doses of the product but enrolment was stopped earlier this year when Acorda decided to pursue a once-daily formulation. Having reached 50% of target enrollment, Acorda is conducting an unblinded analysis of the Phase III trial data. Together with Phase I results from multi-dose pharmacokinetic testing for once daily dalfampridine also expected in the fourth quarter, the data will inform the design of the planned Phase III post-stroke program using the once daily formulation; Acorda plans to run two concurrent pivotal trials in PSWD in mid-2017.
And some better news could come for Alnylam Pharmaceuticals Inc. following last week’s failure of its lead candidate revusiran, with Phase II data due to be presented on Nov. 15 in a late-breaking session at the American Heart Association meeting for its PCSK9 candidate ALN-PCSsc, a systemically delivered RNAi therapeutic, being developed with The Medicines Company. (Also see "Alnylam's 'Day After' Revusiran Failure Bad, Maybe Not Catastrophic" - Scrip, 6 Oct, 2016.)
ALN-PCSsc targets both intracellular and extracellular PCSK9, thereby phenocopying the human genetics observed in loss of function or null human PCSK9 mutations. The ORION-1 Phase II data should show whether the product is likely to be effective in subjects with atherosclerotic cardiovascular disease (ASCVD) or risk equivalent ASCVD and elevated LDL-C when given as biannual or quarterly sc injections. This more convenient dosing schedule would differentiate it from the leading PCSK9 inhibitors Repatha and Praluent, and compensate for its late arrival on the market. (Also see "Alnylam, Medicines Company PCSK9 Drug Has Quarterly Dose Potential" - Scrip, 30 Aug, 2015.)
The fourth quarter is pivotal for Cempra Inc. and its lead antibiotic candidate, solithromycin, for the treatment of community-acquired bacterial pneumonia (CABP). FDA decisions are due for both oral and intravenous formulations on Dec. 27 and 28, respectively, following an Antimicrobial Drugs Advisory Committee meeting on Nov. 4.
Solithromycin is a highly potent next-generation macrolide which has activity against most macrolide-resistant CABP pathogens. This activity is driven by its ability to interact with three sites on the bacterial ribosome, compared with the single binding site of first- and second-generation macrolides. It is the first macrolide since azithromycin to have the potential to be administered both orally and intravenously and is more active than azithromycin or clarithromycin against most macrolide-susceptible bacteria, note analysts at Biomedtracker.
Cempra’s two registrational studies both met the primary endpoint of statistical non-inferiority (10% non-inferiority margin) at the early clinical response. The incidence of infusion site reactions seen with IV solithromycin (34.3% vs. 13.1% with moxifloxacin) raised concerns but this is unlikely to be a major factor given the more severe nature of illness in patients requiring rapid IV administration. “If Cempra can avoid safety concerns from the FDA and have a positive committee meeting outcome, solithromycin could potentially be a blockbuster antibiotic going into 2017.” (Also see "ICAAC 2015: Cempra CEO Sees Solithromycin Potential Beyond Infectious Diseases" - Scrip, 22 Sep, 2015.)
The fourth quarter should also see top-line data for one of RedHill Biopharma Ltd.’s lead drug candidates, RHB-104, for the treatment of moderate-to-severe active Crohn’s disease and multiple sclerosis (MS), from the Phase III MAP US study. RHB-104 is a single capsule, oral combination therapy containing rifabutin, clarithromycin and clofazimine, for the potential treatment of Mycobacterium avium spp paratuberculosis (MAP) infection, which is thought to be a disease-promoting factor in Crohn's disease. RHB-104 has US orphan drug status for the pediatric Crohn’s population.
Staying with anti-infectives, two products for use against hepatitis B infection have PDUFA dates slated by the end of the year. Gilead Sciences Inc. should hear back from the FDA on Nov. 11 on its application for tenofovir alafenamide (TAF) for the treatment of adults with chronic HBV infection. TAF also awaits approval in Europe and Japan with a CHMP opinion expected to occur between November, 2016 and February, 2017. (Also see "Gilead's New Hep B Treatment Shows Safety Benefit But Is It Enough?" - Scrip, 6 Jan, 2016.)
TAF is a prodrug of tenofovir, the active agent in Viread (tenofovir disoproxil fumarate, TDF), and designed to yield higher concentrations in lymphoid tissue with lower levels in plasma. The lower dose required for TAF allows for easier formulation with other drugs into a single tablet. TAF is expected to be approved for HBV as it has similar efficacy to that of Viread, but with better long-term safety on bone density and renal measures.
The FDA is also expected to make a decision regarding the biologics licence application (BLA) for Dynavax Technologies Corp.’s prophylactic vaccine Heplisav by Dec. 15. An FDA advisory committee was originally scheduled to review the application for Heplisav on Nov. 16, but the FDA informed Dynavax that the meeting was cancelled and remaining questions would be addressed via the normal process.
Heplisav is based on Dynavax’s proprietary immunostimulatory sequence, which specifically targets Toll-like receptor 9 to stimulate an innate immune response. Dynavax originally submitted a BLA for Heplisav to the FDA in April 2012, but the company received a complete response letter in May 2013, following a negative vote at an advisory committee meeting based on safety concerns.
The company then conducted the Phase III HBV-23 study to compared the safety and immunogenicity of Heplisav with GlaxoSmithKline PLC’s approved vaccine Engerix-B (GSK). “If approved, Heplisav could become a major competitor for Engerix-B, given the higher seroprotection rate and the lower frequency of treatment,” Biomedtracker said. (Also see "Heplisav-B Review Still On Track Even After Cancelled Advisory Cmte., Dynavax Says" - Pink Sheet, 6 Sep, 2016.)
Best Of The Rest
More Phase III data are expected to report for Rigel Pharmaceuticals Inc.’s big hope fostamatinib. The oral syk kinase inhibitor is under development for the treatment of immune thrombocytopenic purpura (ITP) as its lead indication. The results of the second of two identical studies are due in late October or early November to add to those from the first trial reported in August that showed a narrow benefit with the product. (Also see "Rigel Optimistic On Fostamatinib Despite Narrow Phase III Benefit" - Scrip, 30 Aug, 2016.)
“Given the positive yet preliminary nature of these results, much of the regulatory and commercialization milestones will depend on substantiating results in the second Phase III study,” Biomedtracker analysts said. Together, the trials should support and NDA submission planned for 2017.
Synergy Pharmaceuticals Inc. expects to report top-line data from two studies that it hopes will support a wider indication for its guanylate cyclase C (GC-C) receptor agonist plecanatide (SP-304) by year end. Synergy is developing the drug in the first instance for the treatment of chronic idiopathic constipation (an NDA for this was filed in January 2016, with a PDUFA target action date of Jan. 29, 2017), but also wants to market it for irritable bowel syndrome with constipation. The pivotal Phase III program of plecanatide for this patient population consists of two identical studies. With an sNDA filing planned for the first quarter of 2017 in this indication, these pivotal results will play a key role in how the Synergy proceeds.