FDA approved a BLA for Repatha evolocumab from Amgen Inc. (NASDAQ:AMGN), making it the second mAb against PCSK9 to gain U.S. approval. FDA approved Praluent alirocumab from Sanofi (Euronext:SAN; NYSE:SNY) and Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) on July 24 (see BioCentury Extra, July 24).
The agency approved Repatha as an adjunct to diet and maximally-tolerated statin therapy in adults with heterozygous or homozygous familial hypercholesterolemia (HeFH or HoFH), or clinical atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of LDL cholesterol.
In June, a FDA panel voted 15-0 to support approval of Repatha to treat homozygous familial hypercholesterolemia (HoFH), and 11-4 to treat other forms of hyperlipidemia. (see BioCentury Extra, June 10).
Praluent's approved indication is similar to Repatha's, but does not include homozygous familial hypercholesterolemia.
Amgen said Repatha would be available in the U.S. next week at a wholesale acquisition cost (WAC) of $542.31 for a single injection, or $14,100 annually. The company said it would work with payers to provide "innovative pricing programs" linked to efficacy.
Last month, Sanofi and Regeneron priced Praluent at $40 per day, or $14,600 per year.
In March, payers told BioCentury they would restrict access to the new PCSK9 inhibitors until both were approved, with an eye to offering exclusive formulary status to Repatha or Praluent in exchange for discounts (see BioCentury, March 9).
Last month, Repatha was approved in the EU with a broader label including primary hypercholesterolemia and mixed dyslipidemia (see BioCentury Extra, July 21).
Esperion Therapeutics Inc. (NASDAQ:ESPR) is pursuing approval of ETC-1002 in the same indication for which Praluent is approved. The company intends to start a Phase III trial by YE15 of the AMP-activated protein kinase (AMPK) activator and ATP citrate lyase (ACLY) inhibitor.
Amgen gained $1.74 to $155.72 on Thursday. FDA announced the approval after market close.
uniQure N.V. (NASDAQ:QURE) has shifted its attention from Glybera alipogene tiparvovec to new gene therapy candidates in its pipeline.
On Thursday, the company said FDA has required an additional trial of Glybera to support a potential BLA submission to treat lipoprotein lipase (LPL) deficiency, and CEO Jorn Aldag told BioCentury the company has "moved on from Glybera. There are other milestones ahead."
He said the company is still evaluating whether to pursue U.S. approval of Glybera, and expects to make a decision this year.
uniQure gained $0.62 to $25.23 on Thursday.
Aldag called Glybera a "validation case" for uniQure's platform and said the company now is concentrating on its hemophilia B and Sanfiippo B programs.
This half, uniQure plans to report data from the first dose cohort of its Phase I/II trial of AMT-060 in hemophilia B. Data from the trial's second dose cohort are expected in 2016.
uniQure also said partner Institut Pasteur plans to present data this half from a Phase I/II trial of an AAV5-based gene therapy to treat Sanfilippo B, which Aldag said "could be the first proof-of-concept for a gene therapy for a lysosomal storage disease."
uniQure plans to move forward with a Phase IV study of Glybera in the U.S. in early 2016. The trial will support a post-approval requirement in the EU and was intended to support a BLA filing as well. But Aldag said the planned endpoints did not meet FDA's requirements and that the agency "would like to see a clear link between the drug and its clinical benefit measured some other way."
Further discussion with FDA would be needed to define the endpoints, he said.
The adeno-associated virus (AAV) vector that delivers lipoprotein lipase is approved in the EU, where it is partnered with Chiesi Farmaceutici S.p.A. (Parma, Italy).
Amgen Inc. (NASDAQ:AMGN) filed an emergency motion with the U.S. Court of Appeals for the Federal Circuit (CAFC) for an injunction to further delay the launch of Zarxio filgrastim-sndz from the Sandoz unit of Novartis AG (NYSE:NVS; SIX:NOVN) pending a potential en banc review of the case.
FDA approved Zarxio, a biosimilar of Amgen's Neupogen filgrastim methionyl human G-CSF, on March 6. In July, a CAFC ruling barred Sandoz from launching Zarxio until after Sept. 2; the court ruled that a BLA applicant planning to market a biosimilar may only give the required 180 days' notice to the sponsor of its reference drug after FDA has approved the biosimilar (see BioCentury Extra, July 21).
In July, the CAFC also upheld a district court ruling that Sandoz did not violate the Biologics Price Competition and Innovation Act of 2009 (BPCIA) when it refused to provide its BLA and manufacturing information to Amgen.
Last week, Amgen and Sandoz filed separate petitions for a rehearing en banc. Amgen argued that the CAFC erred when it ruled biosimilar applicants are not required to provide its BLA and manufacturing information to the sponsor of its reference drug. Sandoz's petition said the CAFC's ruling will delay patient access to all biosimilars "for six months longer than Congress intended" and said the court should require Amgen to post a bond sufficient to cover the harm Sandoz has suffered from its delayed launch of Zarxio. Each party's response to the petitions is due Sept. 8
Sandoz intends to file its opposition to Amgen's emergency motion by Monday, Aug. 31.
Genmab A/S (CSE:GEN) rose DKK49.50 to DKK610 on Thursday after data from a Phase I/II trial of daratumumab (HuMax-CD38) as monotherapy in relapsed or refractory multiple myeloma (MM) patients were published in The New England Journal of Medicine.
In the Phase II portion of the trial, 16 mg/kg of daratumumab led to a 36% overall response rate (ORR), including two complete responses, two very good partial responses and 11 partial responses. Patients who had received two or three prior lines of therapy had a 56% ORR compared with a 23% rate in more heavily pretreated patients.
Patients receiving 16 mg/kg had a median of four prior lines of therapy and 64% were refractory to both Velcade bortezomib and Revlimid lenalidomide.
Patients received either 8 mg/kg or 16 mg/kg doses. Genmab said its partner, the Janssen Biotech Inc. unit of Johnson & Johnson (NYSE:JNJ), will use the 16 mg/kg dose in future studies of the human mAb against CD38.
Among responders in the high-dose group, the 12 month progression-free survival rate was 65%. The 12 month overall survival (OS) rate among all patients in the high-dose group was 77% (95% CI: 58, 88).
The data were included in Janssen's BLA submission last month to FDA for daratumumab to treat MM patients who have received at least three prior lines of therapy including both a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), or who are double refractory to a PI and IMiD.
In data from a Phase II trial presented at this year's American Society of Clinical Oncology (ASCO) meeting, daratumumab was the first mAb to show efficacy in high-risk MM patients who had exhausted all other therapies. Treatment with 16 mg/kg of daratumumab led to an ORR of 29.2% in MM patients who had received a median of five prior lines of therapy (see BioCentury, June 8).
Janssen gained exclusive, worldwide rights to daratumumab from Genmab under a 2012 deal.
FDA released draft guidance and a proposed rule on biosimilar naming. Both documents propose to give each biological product a shared non-proprietary "core name" plus a unique four-letter suffix to associate biologic products with non-interchangeable biosimilars, but distinguish between them.
The draft guidance proposed that each biologic and biosimilar receive a hyphenated "proper name" joining two parts: a "core name," which FDA describes as a non-proprietary name containing scientific information about the compound, plus a suffix to differentiate among non-interchangeable reference products and biosimilars.
FDA did not take a stance on whether to include a distinguishing suffix for interchangeable products; it will accept comments on the issue until Oct. 27.
Application sponsors would submit four-letter suffixes to FDA for approval; suffixes must be devoid of meaning and without any promotional elements or resemblance to other products. The naming system would affect both new and previously approved products.
Last year, the World Health Organization proposed a similar biosimilar naming system. FDA spokesperson Stephen King told BioCentury that unlike WHO's system, FDA will consider eliminating the distinguishing suffix for interchangeable products (see BioCentury Extra, Sept. 24, 2014).
FDA released a draft guidance addressing interchangeability in April (see BioCentury Extra, May 12).
This week, FDA also proposed a new rule that would give new proper names to Zarxio filgrastim-sndz from the Sandoz unit of Novartis AG (NYSE:NVS; SIX:NOVN); TevaGrastim tbo-filgrastim from Teva Pharmaceuticals Industries Ltd. (NYSE:TEVA); Remicade infliximab from Johnson & Johnson (NYSE:JNJ); and Neupogen filgrastim, Neulasta pegfilgrastim and Epogen epoetin alfa from Amgen Inc. (NASDAQ:AMGN).
Zarzio, a biosimilar of human granulocyte colony-stimulating factor (G-CSF), would receive the proper name filgrastim-bflm. Its reference product Neupogen would be called filgrastim-jcwp. TevaGrastim, a short-acting recombinant form of G-CSF, would be named filgrastim-vkzt and Neulasta, a pegylated G-CSF, would be named pegfilgrastim-ljfd.
The proper name of Epogen, an erythropoietin (EPO) receptor agonist, would be epoetin alfa-cgkn. Remicade, a chimeric mAb against tumor necrosis factor (TNF) alpha, would be called infliximab-hjmt.
Comments on the proposed rule are due Nov. 11.
HHS's Health Resources and Services Administration (HRSA) issued draft guidance on the 340B program that addresses some of industry's concerns with the program. The guidance includes a clearer definition of 340B-eligible patients.
The 340B program is intended to provide discounted outpatient drugs to hospitals that serve a disproportionate share of poor and uninsured patients. The 340B hospitals can then dispense the discounted drugs to their non-Medicaid outpatients and use the savings to pay for the care of indigent patients.
However, the number of 340B-eligible entities and discounted drugs sold to those entities has grown over the last several years, and industry has said some hospitals are not using the money to pay for charity care and are dispensing the discounted drugs to individuals who are not patients of the hospital (see BioCentury, May 19, 2014).
In the draft, HRSA clarifies which patients would be eligible for 340B: those who receive care at the hospital and who have received a prescription from a provider directly affiliated with the hospital. The rule notes that a patient would be ineligible if the drug is dispensed while they are still an inpatient; if the only service provided by the hospital or provider is to dispense or infuse the drug to the patient; if the patient's physician has credentials or privileges at the hospital but who is not an employee of the hospital; or if the patient is an employee of the hospital but may get care elsewhere.
Additionally, if patients of the covered entity choose to have their prescription filled at a pharmacy not affiliated with the hospital, the drug would be ineligible for the discount.
The guidance also would allow manufacturers to audit covered entities if the manufacturer "has reasonable cause" to believe that the entity is providing duplicate discounts to Medicaid patients or diverting drugs to ineligible patients.
The draft did not address how hospitals should be using the revenues from 340B discounted drugs.
In separate statements, the Biotechnology Industry Organization (BIO) as well as the industry group AIR340B said they are still reviewing the proposed guidance with the hope that it will increase program accountability and oversight.
The hospital group 340B Health (formerly Safety Net Hospitals for Pharmaceutical Access) also is reviewing the guidance. "There are gray areas in the program and we look forward to having more clarity," the group said in a statement, adding that it hopes "safety-net healthcare providers will not find themselves limited in their ability to meet their missions to treat the underserved."
The draft guidance will be published in the Federal Register on Friday. Comments are due Oct. 27.
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