Spark Therapeutics Inc. (NASDAQ:ONCE) slipped $3.51 to $55.01 on Monday after two studies in the New England Journal of Medicine showed that treatment effects of gene therapies declined over time in patients with Leber congenital amaurosis (LCA). Researchers had hoped the effects would be permanent.
Neither study included any of Spark's therapies. The company is conducting a Phase III trial of SPK-RPE65 (AAV2-hRPE65v2) to treat LCA caused by mutations in the RPE65 gene.
Like SPK-RPE65, the gene therapies used in the NEJM studies consisted of an adeno-associated virus (AAV) delivering the retinal pigment epithelium-specific protein 65kDa (RPE65) gene.
In one study, six out of 12 patients showed increased sensitivity to light. The effects peaked at 6-12 months, then declined over the next two years. In the second, three evaluable patients who were followed for 5-6 years showed increased sensitivity to light that peaked between 1 and 3 years and then started to decline.
Spark co-founder and CEO Jeffrey Marrazzo told BioCentury that 2-4 year follow-up data from the company's second Phase I/II trial of SPK-RPE65 to treat LCA, which used the optimized dose and volume of the treatment, has shown no loss of visual sensitivity or mobility of treated patients.
Marrazzo said SPK-RPE65 differs from the therapies in the NEJM studies in four ways that could make it more effective. He said Spark's manufacturing process removes empty capsids that would compete with capsids carrying the therapeutic gene; Spark's formulation includes a diluent to facilitate injection; SPK-RPE65 includes an optimized promoter; and patients in Spark's trials were pretreated both topically and systemically with immunomodulators to prevent the immune system from attacking transfected cells, while patients in other studies were pretreated only topically.
Marrazzo said Spark will not alter its development plans for SPK-RPE65 based on the studies. "There's nothing about these papers that's new to us; we're not changing anything," he said.
SPK-RPE65 has Orphan drug and breakthrough therapy designations to treat LCA. The company expects data in 2H15 from a Phase III trial of SPK-RPE65 to treat LCA.
Ocular gene therapy developer Avalanche Biotechnologies Inc. (NASDAQ:AAVL), which has named LCA as an area of interest but has not disclosed a specific program to treat the disorder, dipped $2.17 to $31 on Monday. Avalanche and Spark were the two largest daily decliners among BioCentury 100 companies.
Bayer AG (Xetra:BAYN) gained exclusive, worldwide development and commercialization rights to anticoagulant candidate ISIS-FXIRx from Isis Pharmaceuticals Inc. (NASDAQ:ISIS) for $100 million up front.
Isis is eligible for a $55 million milestone after completing a Phase II trial of ISIS-FXIRx in patients with compromised kidney function, $320 million in additional milestones, and tiered royalties in the low to high 20% range.
Bayer markets the anticoagulant Xarelto rivaroxaban. The company plans to study ISIS-FXIRx to treat patients who are unable to use currently available anticoagulants, including patients at high risk of bleeding.
ISIS-FXIRx, a Factor XI antisense inhibitor, reduced by sevenfold the rate of venous thromboembolism (VTE) vs. enoxaparin in a Phase II trial to prevent VTE in patients undergoing total knee replacement surgery (see BioCentury Extra, May 22, 2014).
Isis rose $1.42 to $59.66 on Monday; Bayer gained EUR 0.20 to EUR 130.10.
WuXi PharmaTech Inc. (NYSE:WX) said it started construction of a biologics manufacturing facility in Wuxi City that will be the largest in China. The company expects to complete construction by January 2017.
The plant will house 14 2,000-liter disposable bioreactors for fed-batch cell culture and two 1,000-liter bioreactors for perfusion runs. VP of Corporate Alliances Hui Cai said it will be used for "near-term clinical and long-term commercial" production of biologics.
In March, WuXi unveiled plans to build a cell therapy manufacturing facility in Philadelphia to produce chimeric antigen receptor T (CAR T) cells and other cancer immunotherapies. WuXi expects the Philadelphia plant to come on line in mid-2016 (see BioCentury Extra, March 13).
Metabolic play Intarcia Therapeutics Inc. (Boston, Mass.) named Michael Williams COO. Williams was head of global marketing at the Tokyo division of Takeda Pharmaceutical Co. Ltd. (Tokyo:4502).
Neurology play Impax Laboratories Inc. (NASDAQ:IPXL) named Deborah Penza SVP and chief compliance officer. Penza was chief compliance officer at Actavis plc (NYSE:ACT).
Metabolic play Ocera Therapeutics Inc. (NASDAQ:OCRX) said chief development officer Rajiv Patni will step down June 1. Franck Rousseau, former chief development officer and CMO, will lead clinical development in the interim until Ocera replaces Patni.
Anti-infective play AmpliPhi BioSciences Corp. (OTCBB:APHB) named Scott Salka CEO. He replaces interim CEO Jeremy Curnock Cook, who will remain chairman. Salka is CEO of Aspyrian Therapeutics Inc., which told BioCentury he will leave the company soon.
Neurology play Trevena Inc. (NASDAQ:TRVN) named Carrie Bourdow SVP and chief commercial officer. Bourdow was VP of marketing, reimbursement and operations at Cubist Pharmaceuticals Inc., which Merck & Co. (NYSE:MRK) acquired.
Autoimmune play Synthetic Biologics Inc. (NYSE-M:SYN) named Steven Shallcross CFO, treasurer, and secretary, effective June 1. Shallcross is EVP and CFO at Nuo Therapeutics Inc. (OTCQX:NUOT).
Vaccine play Immunomic Therapeutics Inc. (Hershey, Pa.) hired Eric Winzer as CFO. Winzer was CFO at OpGen Inc. (Gaithersburg, Md.).
Diagnostic play Cesca Therapeutics Inc. (NASDAQ:KOOL) said CFO Dan Bessey has resigned. Michael Bruch, the company's controller, will be interim CFO.
Biochemical supply company Genovis AB (SSE:GENO) promoted Fredrik Olsson to CEO from VP, replacing founder Sarah Fredriksson. The company's nomination committee proposed that Fredriksson be elected chairperson of its board; Fredriksson also will continue in an operations role at Genovis subsidiary GeccoDots AB.
CytRx Corp. (NASDAQ:CYTR) jumped $0.71 (19%) to $4.41 on Monday after the company presented data from two Phase Ib trials of combinations including its aldoxorubicin to treat sarcomas and solid tumors.
An interim analysis of a Phase Ib study testing aldoxorubicin plus ifosfamide and mesna as first-line therapy for patients with locally advanced, unresectable and/or metastatic sarcomas showed that one out of seven evaluable patients had a complete response after five treatment cycles.
In the second trial, treatment with aldoxorubicin plus gemcitabine as second-line therapy led to partial responses in three of seven patients with advanced, unresectable, metastatic solid tumors.
CytRx said the combinations were well tolerated in both studies, but did not provide detailed safety data.
The company expects to finish dose-finding in each trial in 2H15, after which it will start enrolling additional patients at the maximum tolerated doses of the combinations.
Aldoxorubicin is a 6-maleimidocaproyl hydrazone prodrug of doxorubicin.
Tocagen Inc. (San Diego, Calif.) said it plans to start a Phase II/III trial in 4Q15 of Toca 511 vocimagene amiretrorepvec and Toca FC to treat patients undergoing resection for first or second recurrence of glioblastoma multiforme (GBM) or anaplastic astrocytoma. The trial will compare the combination of Toca 511 and Toca FC vs. standard of care, which includes lomustine, temozolomide or Avastin bevacizumab from the Genentech Inc. unit of Roche (SIX:ROG; OTCQX:RHHBY).
Toca 511 is a retroviral replicating vector that delivers the gene encoding cytosine deaminase (CD), an enzyme that converts the prodrug 5-fluorocytosine (5-FC) into the active form 5-fluorouracil (5-FU). Toca FC is an extended-release version of the oral antifungal 5-flucytosine.
Tocagen also reported interim Phase I data for the combination therapy at a meeting of the American Association of Neurological Surgeons and Congress of Neurological Surgeons Section on Tumors.
In one Phase I trial of 38 patients with recurrent high grade glioma, Toca 511 administered into the resection cavity wall at the time of surgery followed by oral Toca FC led to median overall survival (OS) of 13.7 months. In patients with high grade glioma at first or second recurrence, the anticipated patient population for the Phase II/III trial, treatment with the combination led to median OS of 14.6 months.
In a second Phase I trial to treat recurrent high grade glioma, Toca 511 was administered transcranially into the tumor followed by oral Toca FC and led to a one-year OS rate of 45%.
Historical OS in these patients is seven to eight months.
In a third Phase I study, Toca 511 was given IV to patients with recurrent glioblastoma who were scheduled for tumor resections. Patients subsequently received Toca 511 injections in the resection cavity and oral Toca FC. Viral DNA encoding CD and the CD protein were detected in resected tumor samples and Tocagen said the findings demonstrate the potential to treat other types of tumors with systemic infusions. The company plans to study Toca 511 and Toca FC as IV therapy to treat metastatic solid tumors but declined to disclose a development timeline.
Acceleron Pharma Inc. (NASDAQ:XLRN) announced preliminary results from a 44-patient, open-label Phase II dose-escalation trial of luspatercept (ACE-536) to treat lower risk myelodysplastic syndromes (MDS).
In a high-dose group receiving 0.75-1.75 mg/kg every three weeks, 22 (63%) of 35 patients met the primary efficacy endpoint of a hemoglobin increase of ≥1.5 g/dL for ≥2 weeks or a reduction of ≥4 units or ≥50% reduction in transfusions over 8 weeks. In a low-dose group receiving 0.125-0.5 mg/kg, 3 (33%) of 9 patients met the same endpoint. The high-dose group also had a 54% response rate in achieving the International Working Group (IWG) hematologic improvement-erythroid (HI-E) threshold of efficacy, compared to 22% in the low-dose group. Acceleron reported two serious adverse events "possibly related" to treatment: grade 3 muscle pain and grade 3 worsening of general condition.
The data were presented at the MDS Foundation's International Symposium on MDS in Washington, D.C.
Acceleron and Celgene Corp. (NASDAQ:CELG) partnered in 2011 to develop and commercialize luspatercept. They plan to start a Phase III trial by YE15 of the modified activin receptor type 2B (ACVR2B) fusion protein that inhibits several ligands in the transforming growth factor (TGF) beta superfamily. Final Phase II results will be presented at the American Society for Hematology meeting in December. Acceleron and Celgene also intend to start a Phase III study of luspatercept by YE15 to treat beta-thalassemia intermedia (see BioCentury Extra, Dec. 8, 2014).
Acceleron gained $0.48 to $29.22 on Monday, while Celgene shed $0.65 to $109.90.
TaiGen Biopharmaceuticals Holdings Ltd. (GreTai:4157) began a Phase I/II trial in China of burixafor (TG-0054), a CXC chemokine receptor 4 (CXCR4) inhibitor, to treat relapsed or refractory acute myelogenous leukemia (AML).
The open-label, dose-finding study in up to 15 patients will examine the safety and efficacy of burixafor in combination with fludarabine and cytarabine. The study's endpoints include complete response (CR), disease-free survival (DFS), and overall survival (OS). TaiGen has completed a Phase II study of burixafor in the U.S. to treat multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), and Hodgkin's disease.
Wang JianXiang of the Institute of Hematology and Blood Diseases Hospital in Tianjin is leading the new trial.
In 2010, Taipei and Beijing signed a Cross-Strait Cooperation Agreement on Medicine and Public Health Affairs to collaborate on drug reviews, regulations and clinical trials.
TaiGen gained $1.70 to $30.05 on Monday.
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