Amgen Inc. (NASDAQ:AMGN) said it is withdrawing from a collaboration with AstraZeneca plc (LSE:AZN; NYSE:AZN) to develop and commercialize brodalumab because Amgen is concerned the compound will require restrictive labeling based on suicidal ideation and behavior seen in clinical trials.
Amgen spokesperson Trish Hawkins told BioCentury there have been "suicides in the single digits across the entire brodalumab program involving more than 5,000 patients."
AZ said it will evaluate data from brodalumab trials and decide how to proceed with the program. Spokesperson Michele Meixell told BioCentury the company does not believe there is a causal association between brodalumab and suicidal ideation and behavior.
The companies released data last year from three Phase III studies of the human IgG2 mAb against IL-17 receptor (IL17R; IL17RA) to treat moderate to severe plaque psoriasis. A Phase III study to treat psoriatic arthritis is ongoing, and a Phase II trial to treat axial spondyloarthritis is due to begin in June. Amgen previously said it planned to submit a BLA and an MAA for brodalumab to treat moderate to severe plaque psoriasis mid-year.
Amgen and AZ partnered in 2012 to jointly develop and commercialize five mAbs from Amgen's inflammation portfolio, including brodalumab. AZ will hold rights to brodalumab in all territories excluding certain Asian territories where Kyowa Hakko Kirin Co. Ltd. (Tokyo:4151) has rights. Amgen declined to disclose a program transition timeline. The partnership remains intact for the other four mAbs (see BioCentury, April 9, 2012).
Brodalumab targets the IL-17 receptor, while approved drug Cosentyx secukinumab from Novartis AG (NYSE:NVS; SIX:NOVN) and late-stage candidate ixekizumab from Eli Lilly and Co. (NYSE:LLY) are directed against IL-17A.
Cosentyx secukinumab is approved in the U.S. and EU to treat moderate to severe plaque psoriasis. Its label does not mention suicidal ideation.
In 1Q15 Lilly submitted a BLA to FDA for ixekizumab (LY2439821) to treat moderate to severe plaque psoriasis.
A consortium consisting of Shanghai Fosun Pharmaceuticals Group Co. Ltd. (Shanghai:600196; HKSE:2196), WuXi PharmaTech Inc. (NYSE:WX), HOPU Investments and China Everbright Ltd.'s healthcare fund agreed to acquire Ambrx Inc. (La Jolla, Calif.) for an undisclosed amount. China Everbright said the deal will allow Ambrx to establish a global product development center and expand its business rapidly in China.
Ambrx is developing a pipeline of antibody-drug conjugates, bispecific and multi-specific drug conjugates, and long-acting proteins. The company has received more than $200 million from partnerships with pharmas including Bristol-Myers Squibb Co. (NYSE:BMY), Merck KGaA (Xetra:MRK) and Eli Lilly and Co. (NYSE:LLY).
BMS is conducting Phase II trials of Ambrx's most advanced program, ARX618, a fibroblast growth factor-21 (FGF-21) like protein to treat Type II diabetes. Ambrx's lead unpartnered candidate is ARX788, a preclinical antibody-drug conjugate (ADC) targeting epidermal growth factor receptor 2 (EGFR2; HER2) that is slated to enter clinical testing this year to treat HER2-positive breast cancer.
The parties expect to close the acquisition this quarter.
Last June, Ambrx withdrew plans for an IPO on NASDAQ. As of March 31, 2014, its largest stakeholders included Tavistock (19.3%), Maverick Capital (17.4%), Apposite Healthcare Fund (9.5%), affiliates of Versant Ventures (7.5%) and affiliates of 5AM Ventures (6.9%) (see BioCentury Extra, June 30, 2014).
BMO Capital Markets Corp. advised Ambrx and Latham and Watkins was its counsel. Haynes and Boone served as counsel to the consortium.
The German Institute for Quality and Efficiency in Health Care (IQWiG) said in a dossier assessment that Harvoni ledipasvir/sofosbuvir from Gilead Sciences Inc. (NASDAQ:GILD) had a "hint" of an added benefit in non-cirrhotic patients co-infected with HCV genotype 1 and HIV. The agency said the benefit was non-quantifiable because it was unclear to what extent late complications including liver cancer were preventable in patients in whom the virus was no longer detectable. IQWiG previously said Harvoni had "a hint of a non-quantifiable added benefit" for pre-treated HCV genotype 1 patients and non-cirrhotic treatment-naive HCV genotype 1 patients, and no added benefit in patients with HCV genotype 4 or genotype 3 with decompensated cirrhosis of the liver.
IQWiG also said Otezla apremilast from Celgene Corp. (NASDAQ:CELG) had no added benefit in patients with moderate to severe plaque psoriasis or active psoriatic arthritis. The agency said Celgene did not submit data on Otezla against appropriate comparators and only included data from placebo-controlled trials. IQWiG noted that Celgene did not claim an added benefit for the oral phosphodiesterase-4 (PDE-4) inhibitor in either indication.
Otonomy Inc. (NASDAQ:OTIC) fell $6.19 (20%) to $24.86 on Friday after its OTO-104 missed the primary endpoint in a Phase IIb study to treat unilateral Meniere's disease. Based on positive trends and secondary endpoint results, the company plans to begin the first of two Phase III trials of OTO-104 to treat Meniere's by year end.
The study's primary endpoint was a reduction in vertigo frequency during month 3 compared to a one-month baseline period. Patients receiving OTO-104 had a 61% reduction vs. 43% for placebo (p=0.067).
Otonomy said OTO-104 showed significance on prospectively defined secondary endpoints including definitive vertigo days at month 3 (1.64 for OTO-104 vs. 2.54 for placebo, p=0.03) and change in vertigo severity score from baseline (-0.46 for OTO-104 vs. -0.32 for placebo, p=0.046).
The sustained-release dexamethasone gel delivered via intratympanic injection did not show an effect on the exploratory endpoint of tinnitus.
OTO-104 is Otonomy's second-most advanced program. The company's AuroPro (OTO-201), a sustained-release gel formulation of ciprofloxacin, is under FDA review to treat middle ear effusion in pediatric patients undergoing tympanostomy tube placement (TTP) surgery, with a Dec. 25 PDUFA date.
Cellular Biomedicine Group Inc. (NASDAQ:CBMG) gained $4.51 (14%) to $35.64 on news its chimeric antigen receptor (CAR) T cell therapy targeting CD30 led to partial responses in two of seven patients in a Phase I study to treat progressive relapsed/refractory Hodgkin's lymphoma. Three additional patients had stable disease after receiving the therapy, which consists of T cells expressing a CAR specific to the CD30 antigen.
One patient had an adverse event: five-day self-limiting arthralgias, myalgias and dual knee swelling two weeks after cell infusion.
The study was conducted by Chinese PLA General Hospital (PLAGH). Cellular Biomedicine presented the data at the World Stem Cells & Regenerative Medicine Congress in London on Thursday.
EMA released for consultation draft guidance for gene therapies, saying the document was designed for smaller companies and academics unfamiliar with the regulatory environment.
The document describes the agency's thinking on quality and manufacturing of therapies, including specifications for obtaining vectors and genetic elements and ensuring the purity and stability of batches. The guidance also outlines practices for non-clinical development, with a goal of optimizing dose selection and methods of administration.
According to the guidance, the requirements for efficacy studies of gene therapies should be similar to those of other medicinal products and should adhere to guidelines designed for specific therapeutic areas. The document says alternative approaches, such as studies that lack traditional control groups, are allowable if they can be justified.
A section on clinical studies discusses the agency's thinking on safety and efficacy evaluation as well as follow-up studies and pharmacovigilance planning.
Comments on the draft are due Aug. 31.
State health insurance exchange Covered California approved monthly caps to co-pays on specialty drugs that will range from $150 to $500 per prescription, beginning in 2016.
Bronze plans will have a $500 cap. Platinum, gold and certain silver plans will have a $250 cap, while other silver plans will have a $150 cap. Plan beneficiaries will cover the cost of specialty drugs up to the monthly cap until reaching their maximum out-of-pocket costs, which range from $2,250 to $6,500.
Covered California spokesperson James Scullary said monthly premiums across all four plan levels will rise by less than 1% in 2016 as a result of the caps. Covered California projects that the caps will cause premiums to rise by no more than 3% over three years.
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