The German reimbursement agency G-BA suspended its benefit assessment of gene therapy Glybera alipogene tiparvovec from uniQure N.V. (NASDAQ:QURE). The move followed uniQure's disclosure in an SEC filing that on April 8 it received a rapporteur's assessment report from EMA's Committee for Advanced Therapy Medicinal Products (CAT) that said Glybera lacked efficacy and therefore had a negative benefit-risk balance.
The rapporteur's report is under review at the CAT's monthly meeting, where the committee is considering uniQure's Type II variation application to add six-year follow-up data to the label for Glybera to treat the Orphan disease lipoprotein lipase deficiency (LPLD).
The report will also likely be reviewed at CHMP's April 21-23 meeting, as CAT is the committee that advises CHMP on gene and cell therapies. uniQure noted in its filing that the report is not binding on CAT or CHMP. uniQure CEO Jorn Aldag told BioCentury that the report does invite the company to present supplemental information on the six-year data.
In its announcement, G-BA said it would suspend the benefit assessment so that it could await the decisions of CAT and CHMP. G-BA now expects to make a decision by May 7.
In its SEC filing, uniQure reiterated that an adverse outcome of the review could require it to conduct further post-approval studies or result in the revocation of its MAA in the EU.
Last June, uniQure announced six-year follow-up data from a retrospective analysis of 19 LPLD patients showing that a single administration of Glybera led to about a 50% reduction in pancreatitis events with no cases of severe pancreatitis post-treatment, and a 50% reduction in hospitalization rates due to pancreatitis. Aldag told BioCentury, "When you have a 50% reduction in pancreatitis, you can look at it two ways: That's either very good, or you can say, 'But there still is pancreatitis occurring.'"
Glybera already has a long and difficult regulatory history. It took several attempts before EMA approved the gene therapy in 2012 (see BioCentury, July 30, 2012).
The biotech plans to begin a Phase IV U.S. study in early 2016 of Glybera before submitting a BLA to FDA. The adeno-associated virus (AAV) vector encoding lipoprotein lipase is partnered with Chiesi Farmaceutici S.p.A. (Parma, Italy) in Europe, where Chiesi expects the first patient to receive Glybera in mid-2015.
uniQure shed $0.71 to $26.97 on Friday. Its stock remains up from its April 2 close at $22.86, prior to a deal with Bristol-Myers Squibb Co. (NYSE:BMY), but is off 20% from $33.63 at market close April 7, the day before it received the rapporteur's assessment report and the day it proposed a follow-on offering in which it would raise $88.5 million (see BioCentury Extra, April 10).
Regenerative medicine play Harvard Apparatus Regenerative Technology Inc. (NASDAQ:HART) said CEO David Green resigned. CFO Thomas McNaughton will be interim CEO.
Vaccine developer Immunovaccine Inc. (TSX:IMV) named Fredric Ors CBO. Ors was VP of business development and strategic planning at Medicago Inc.
Bristol-Myers Squibb Co. (NYSE:BMY) stopped the Phase III CheckMate -057 trial early after an independent data monitoring committee concluded that Opdivo nivolumab met the primary endpoint of superiority to docetaxel in improving overall survival in previously-treated patients with advanced non-squamous non-small cell lung cancer (NSCLC).
Spokesperson Carrie Fernandez would not disclose when BMS plans to seek a label extension to treat non-squamous NSCLC. The human IgG4 mAb against programmed cell death 1 (PDCD1; PD-1; CD279) has Fast Track designation in the U.S. to treat NSCLC, renal cell carcinoma (RCC) and melanoma.
In March, FDA approved an sBLA for Opdivo to treat metastatic squamous NSCLC in patients who have progressed on or after platinum-based chemotherapy (see BioCentury Extra, March 4).
FDA first approved the drug in December 2014 to treat unresectable or metastatic melanoma in patients previously treated with the company's Yervoy ipilimumab, including BRAF V600 mutation-positive patients treated with Yervoy plus a BRAF inhibitor (see BioCentury Extra, Dec. 22, 2014).
BMS has worldwide rights to Opdivo from Ono Pharmaceutical Co. Ltd. (Tokyo:4528), excluding Japan, Korea and Taiwan, where Ono and BMS are partnered.
Momenta Pharmaceuticals Inc. (NASDAQ:MNTA) said data demonstrate equivalence between its once-daily Glatopa glatiramer acetate and blockbuster multiple sclerosis (MS) drug Copaxone from Teva Pharmaceutical Industries Ltd. (NYSE:TEVA). On Thursday, FDA approved Glatopa, the first generic version of Copaxone.
An abstract released in advance of next week's annual meeting of the American Academy of Neurology described no differences in the structure and function of Glatopa and Copaxone and reported equivalence of physiochemical and biological properties. In a second study, Glatopa was equivalent to Copaxone as measured by its effect on changes in T cell gene expression.
Glatopa was developed under a partnership between Momenta and the Sandoz unit of Novartis AG (NYSE:NVS; SIX:NOVN) (see BioCentury Extra, April 16).
Momenta gained $0.49 to $17.57 on Friday.
An abstract released ahead of the American Academy of Neurology meeting said RG7800 from Roche (SIX:ROG; OTCQX:RHHBY) demonstrated proof of mechanism in a Phase I trial by showing a dose-dependent effect on splicing of survival of motor neuron 2 centromeric (SMN2) in healthy volunteers.
Roche began a Phase Ib/IIa trial of RG7800 in November to treat spinal muscular atrophy (SMA). Roche licensed the compound from PTC Therapeutics Inc. (NASDAQ:PTCT) in 2011.
In the Phase I study, healthy subjects received single oral doses of 0.5 mg-90 mg of RG7800. Full length SMN2 mRNA increased and truncated SMN2 mRNA decreased without any effect on SMN1 mRNA, as measured in whole blood samples using a multiplex qRT-PCR assay. Roche will present data at the AAN meeting next week.
Phase III candidate ISIS-SMNRx from Isis Pharmaceuticals Inc. (NASDAQ:ISIS) is the most advanced SMN2 splice modulator in development for SMA. Unlike RG7800, ISIS-SMNRx cannot penetrate the blood brain barrier and is delivered into central nervous system tissues through intrathecal injections (see BioCentury Innovations, Sept. 14, 2014).
Isis was off $0.98 to $65.33 on Friday, in line with declines in the broader markets. PTC slipped $0.25 to $70.74 on Friday.
Medday S.A.S. (Paris, France) said MD1003 met the primary endpoint of disease improvement in a Phase III trial to treat multiple sclerosis (MS).
The primary endpoint was defined as the proportion of patients who showed improvement vs. placebo after nine months of daily treatment with 300 mg MD1003, with confirmation of the result at 12 months. Improvement was defined as either a decrease in Expanded Disability Status Scale (EDSS) score of at least 1 point from a baseline EDSS ≤5.5, or a decrease of 0.5 points from a baseline EDSS ≥6; or improvement of at least 20% in a timed 25-foot walk (TW25) test. The study enrolled 154 patients with baseline EDSS scores of 4.5-7.
Medday said it will report full data on April 24 at the American Academy of Neurology meeting in Washington, D.C. The company did not respond to inquiries about regulatory submissions.
The therapy is a concentrated formulation of D-biotin that targets a rate-limiting enzyme in myelination (see BioCentury, Nov. 24, 2014).
Atlas Venture closed its oversubscribed $280 million Atlas Fund X, the firm's first fund since becoming an exclusively life sciences-focused VC.
Formerly a hybrid firm, Atlas separated its tech and life sciences teams last October, citing diverging ecosystems and business models. The healthcare team retained the Atlas name (see BioCentury, Oct. 6, 2014).
Atlas makes early stage investments in therapeutics developers, including platform companies and asset-centric or build-to-buy companies. The firm plans to seed four to six newcos a year over the next three to four years.
Horizon Pharma plc (NASDAQ:HZNP) raised $433.6 million through the sale of 15.4 million shares at $28.25 in a follow-on underwritten by Citigroup; Jefferies; Cowen; and Morgan Stanley. Horizon proposed the offering Monday, when its shares were valued at $28.49; it priced the offering after market close Wednesday, and gained $1.47 on Thursday before shedding $0.15 to $30.82 Friday. Last week, FDA granted Fast Track designation to Horizon's Actimmune interferon (IFN) gamma-1b to treat Friedreich's ataxia. The company expects to begin a Phase III trial this quarter.
Akebia Therapeutics Inc. (NASDAQ:AKBA) raised $60 million through the sale of 7.3 million shares at $8.25 in a follow-on underwritten by UBS; Morgan Stanley; JMP Securities; Needham; and Brean Capital. Akebia proposed the offering on Tuesday after market close, when its shares were valued at $9.73. Its shares dipped $0.36 to $8.31 on Friday. The company expects to begin a Phase III study this year of AKB-6548, its oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH; EGLN) inhibitor to treat anemia in patients with chronic kidney disease (CKD).
A Congressional effort designed to force companies to have transparent, accountable policies on compassionate, or expanded, access to unapproved drugs has attracted strong support from patient groups and a mixed reaction from industry.
Shire plc (LSE:SHP; NASDAQ:SHPG) expressed support for the Andrea Sloan Compassionate Use Reform and Enhancement Act (HR 909) in an April 14 letter to its sponsor, Rep. Michael McCaul (R-Texas), and leadership of the House Energy and Commerce Committee. HR 909 was included in a discussion draft of the committee's 21st Century Cures legislation. At least two companies, Novartis AG (NYSE:NVS; SIX:NOVN) and GlaxoSmithKline plc (LSE:GSK; NYSE:GSK), have opposed the bill publicly.
HR 909 requires that companies make public an expanded access policy for any drugs that receive breakthrough therapy, Fast Track, or Qualified Infectious Disease Product (QIDP) designations. It does not require companies to provide such access. If expanded access is available, companies must provide a single point of contact for requests, criteria for evaluating requests, and anticipated response time.
Shire's letter states that HR 909 "will ensure patients seeking early access to investigational medicines can clearly understand how a request for compassionate use is made, and what considerations will go into evaluating the request."
In comments about the 21st Century Cures draft, Novartis said it "does not support a statutory mandate linking the development, or posting, of expanded access policies to regulatory designation mechanisms." GSK said it supports voluntary posting of expanded access policies, and opposes linking expanded access disclosures to regulatory designations.
Patient groups that have expressed support for HR 909 include the National Organization for Rare Disorders, the Leukemia and Lymphoma Society, the American Cancer Society, the Oncology Nursing Association, the Ovarian Cancer National Alliance and Kids v Cancer.
In response to stakeholder concerns regarding FDA's proposed plan for regulating laboratory-developed tests (LDTs), FDA and CMS are establishing a joint task force dedicated to LDT oversight. The group will identify redundancies between the regulatory roles of FDA and CMS and clarify requirements for laboratories that will undergo review by both agencies.
FDA released two draft guidance documents in October outlining the agency's plans for LDT oversight. Under the proposed framework, FDA would enforce requirements for establishing a test's analytical validity and clinical validity. CMS would continue to oversee laboratory operations through the Clinical Laboratory Improvement Amendments (CLIA). LDTs have been regulated by CMS under CLIA since 1988, but CLIA does not require premarket review of tests or evidence of clinical validity (see BioCentury, Aug. 11, 2014).
The majority of attendees at a January workshop to discuss FDA's LDT guidance opposed the framework and said FDA guidance should be additive to CLIA but not overly burdensome or duplicative. FDA spokesperson Jennifer Dooren declined to comment on a timeline for a final LDT guidance (see BioCentury Extra, Jan. 9).
In March, the Diagnostic Test Working Group of the Personalized Medicine Coalition proposed an alternative regulatory framework for all in vitro diagnostics, including LDTs.
Merck KGaA (Xetra:MRK) hired Alise Reicin as SVP and head of global clinical development. Reicin was VP, project and pipeline leadership, oncology franchise at Merck & Co. Inc. (NYSE:MRK). The April 16 BioCentury Extra misstated her prior position.
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