Panelists at a meeting of FDA's Peripheral and Central Nervous System Drugs Advisory Committee to discuss Kyndrisa drisapersen from BioMarin Pharmaceutical Inc. (NASDAQ:BMRN) generally agreed that the therapy's efficacy to treat Duchenne muscular dystrophy (DMD) has not been established, although some panelists thought some boys benefited from the treatment.
The biotech argued that while Kyndrisa missed the primary endpoint of a Phase III study in which it numerically improved six-minute walking distance (6MWD) vs. placebo by 10 meters (p=0.42), pooled results from a smaller patient group across three studies showed a consistent direction and magnitude of treatment effect. Kyndrisa significantly improved 6MWD vs. placebo in one dose group of one Phase II study and trended towards improvement in another Phase II study.
But most panelists found the full Phase III data more compelling than post hoc analyses. Though they agreed with BioMarin that using a broad patient population may have skewed the data, they thought more study is needed to determine which subgroups of patients are more likely to respond.
Fifteen panelists voted that the Phase III data weakened the persuasiveness of the Phase II data, while two voted that it had no effect. Six voted that dystrophin expression data weakened their interpretation of clinical results, while 10 voted that it had no effect. None voted that either data set strengthened their interpretation of the results. One panelist did not vote on the dystrophin question.
Most DMD community representatives who spoke at the meeting asked FDA to approve the treatment so that they could make their own benefit-risk assessments even if efficacy has not been conclusively established.
FDA officials also raised concerns about safety issues including thrombocytopenia and renal complications. There were no deaths in the studies.
But panelists agreed that DMD patients and caregivers could understand and make informed decisions around the safety risks, and did not find them insurmountable given the progressive lethality of the disorder.
Kyndrisa, an antisense oligoribonucleotide that induces exon 51 skipping on the dystrophin gene, is under review to treat DMD in patients with mutations amenable to exon 51 skipping. The PDUFA date is Dec 27. BioMarin's stock did not trade on Tuesday.
FDA and EMA each approved multiple drugs early this week, including the first approval for Portrazza necitumumab (LY3012211) from Eli Lilly and Co.(NYSE:LLY). FDA approved Portrazza in combination with chemotherapy as a first-line treatment for squamous non-small cell lung cancer (NSCLC). Lilly intends to launch and price the human IgG1 mAb against EGFR within weeks.
FDA also approved Opdivo nivolumab from Bristol-Myers Squibb Co. (NYSE:BMY) as a single agent for patients with previously untreated BRAF V600 wild-type advanced melanoma. In October, the agency approved the human IgG4 mAb against PD-1 in combination with BMS's Yervoy ipilimumab for the same indication. FDA has also approved the drug to treat advanced renal cell carcinoma and metastatic squamous non-small cell lung cancer (NSCLC) (see BioCentury Extra, Nov. 23).
The European Commission granted conditional approval to Blincyto blinatumomab from Amgen Inc. (NASDAQ:AMGN) to treat adults with Philadelphia chromosome-negative relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL). The EC also approved Entresto sacubitril/valsartan from Novartis AG (NYSE:NVS; SIX:NOVN) to treat adults with symptomatic chronic heart failure with reduced ejection fraction, and Elocta efmoroctocog alfa from Biogen Inc. (NASDAQ:BIIB) and Swedish Orphan Biovitrum AB (SSE:SOBI) to treat hemophilia A.
In September, EMA's CHMP recommended approval of the three drugs; FDA has already approved all three. Blincyto is a bispecific T cell engager (BiTE) against CD19. Entresto is a crystalline complex of valsartan and sacubitril in an equimolar ratio. Elocta is a long-acting recombinant fusion protein consisting of the Fc domain of human IgG1 attached to Factor VIII (see BioCentury Extra, Sept. 25).
A study published Monday in JAMA Internal Medicine found that HCV drug Harvoni sofosbuvir/ledipasvir from Gilead Sciences Inc. (NASDAQ:GILD) was cost-effective across all ranges of disease severity.
The study assessed the benefits and costs of Harvoni on a simulated population of 1,000 60-year-old HCV patients. Researchers found that treatment with Harvoni at earlier stages of liver fibrosis resulted in a gain in quality-adjusted life years (QALYs), including increases of 2.27 QALYs for fibrosis scores of F3 vs. F4; 0.55 QALYs for F2 vs. F3; and 0.14 QALYs for F1 vs. F2.
Using the average wholesale acquisition cost (WAC) of $94,500 for 12 weeks of Harvoni therapy, the study found that when patients with fibrosis scores of F2 or higher received the drug, the cost per QALY gained was <$50,000. For patients with fibrosis scores of F1, the cost per QALY gained was $81,165, which was still less than the $150,000 threshold the group set for Harvoni to be considered cost-effective.
Researchers at the University of California San Francisco and the Institute for Clinical and Economic Review (ICER) conducted the study. The group also published supplemental analyses showing that Viekira Pak from AbbVie Inc. (NYSE:ABBV) was cost-effective regardless of fibrosis status.
Earlier this year, several private payers and PBMs in the U.S. granted Harvoni exclusive or co-exclusive status on their formularies in exchange for undisclosed discounts. However, in many cases they continued to limit Harvoni's access to patients with fibrosis scores of F3 or greater. Express Scripts Holding Co. (NASDAQ:ESRX) granted Viekira Pak exclusive status without restrictions on disease severity (see BioCentury Jan. 19).
Uni-Bio Science Group Ltd. (HKSE:690) gained exclusive, worldwide rights to mitiglinide from Jiangsu Hansoh Pharmaceutical Co. Ltd. (Lianyungang, China). Uni-Bio said China FDA has approved the insulin secretagogue as a first or second-line treatment for Type II diabetes.
Financial terms were not disclosed. Uni-Bio said it would seek partners to distribute the drug outside China.
Turing Pharmaceuticals AG (Zug, Switzerland) said it will reduce the list price of toxoplasmosis drug Daraprim pyrimethamine for hospitals by up to 50%.
The company came under fire in September for raising the price of the drug fiftyfold (see BioCentury, Sept. 28).
Beginning early next year, Turing will supply hospitals with free sample packages of Daraprim, as well as smaller bottles to reduce carrying costs.
Turing said it will also continue its outpatient assistance program, which limits monthly co-pays to $10 and provides Daraprim to eligible uninsured patients for free.
XBiotech Inc. (NASDAQ:XBIT) fell $4.50 (34%) to $8.75 on Tuesday after it said Monday after market close that data were compromised from 72 patients in its Phase III study of Xilonix, its human mAb against IL-1 alpha to treat advanced colorectal cancer. The company said it expects the study to have reduced statistical power, but did not disclose the total number of patients in the study and did not respond to inquiries.
XBiotech said 14 patients were given Xilonix or placebo erroneously, 33 did not receive scheduled scans or properly complete evaluations, and 25 dropped out of the study before dosing. The company said it is still receiving patient data and will provide an update on its analysis in about ten days.
The co-primary endpoints of the trial were change in lean body mass as measured by DEXA scan and change in patient-reported symptoms from baseline to week eight. In a Nov. 13 regulatory filing, XBiotech said it could submit an MAA to EMA for Xilonix as soon as YE15.
XBiotech is also conducting a second Phase III trial of Xilonix.
LSP said Tuesday it formed a strategic collaboration with Bristol-Myers Squibb Co. (NYSE:BMY), which made an undisclosed investment in the firm's fifth fund. The investment in LSP 5 is BMS's first in a European healthcare fund. BMS is an LP in U.S.-based Polaris Partners' seventh fund.
LSP said the partners will "work closely together in identifying European breakthrough technologies and products in immuno-oncology and other areas of unmet medical need." BMS VP of Business Development Donnie McGrath joined the fund's advisory board.
LSP General Partner Joachim Rothe told BioCentury BMS made an investment "in the tens of millions." He said LSP now aims to close LSP 5 with EUR 175-EUR 200 million ($186-$212.6 million), above its initial target of EUR 150 million ($159.5 million). The firm had already raised EUR 80 million ($85 million) for the fund by October 2014 (see BioCentury, Oct. 13, 2014).
Pfizer Inc. (NYSE:PFE) and GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) have invested in LSP's previous funds (see BioCentury, March 31, 2014).
The U.K. government partnered with the Bill & Melinda Gates Foundation to launch the five-year, L1 billion ($1.5 billion) Ross Fund, a global health fund to fight infectious diseases. The announcement came as part of the U.K. government's ongoing spending review.
The fund includes L305 million ($462.4 million) earmarked for programs to fight malaria and other infectious diseases. Of the L305 million, L115 million ($174.3 million) goes to developing new drugs, diagnostics and insecticides that combat disease resistance from malaria, tuberculosis and other infections; L100 million ($151.6 million) to R&D of other new products for infectious disease; and L90 million ($136.4 million) to a fund specifically aimed at eradicating malaria.
Separately, charity Alzheimer's Research UK said the country's Medical Research Council will create the Dementia Research Institute to develop diagnostics and treatments for Alzheimer's and other related diseases. The charity said the government will provide up to L150 million ($227.4 million) for the nationwide project, and expects it to be housed at a U.K. university by 2020.
FDA will hold a public meeting March 17, 2016, to discuss psoriasis. The meeting is part of FDA's Patient-Focused Drug Development initiative, in which the agency is holding public meetings to discuss the effects of diseases on daily life, the measures of benefit that matter most to patients and the adequacy of available treatment options.
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