Biotech stocks slumped Wednesday after Time magazine published an interview with Donald Trump in which the president-elect said he would lower drug prices, without saying how he plans to do so.
The BioCentury 100 Index lost 3.3% on Wednesday, with decliners outnumbering gainers 92-8. Despite the losses, the index ended the day 3% higher than its close at 4,792.80 on Nov. 8, before the presidential election results were known. Biotechs' gains outpaced those in the broader markets in the days following the election (see BioCentury, Nov. 14).
On Wednesday, the NASDAQ Biotechnology Index (NBI) and the iShares NASDAQ Biotechnology ETF (IBB) each slipped 2.9%, and the NYSE Arca Biotechnology Index (BTK) fell 3%. The Dow Jones Industrial Average added 1.5%, and the NASDAQ Composite rose 1.1%.
Tmunity Therapeutics Inc. (Philadelphia, Pa.) said it hired Usman Azam as president and CEO. Azam was global head of the cell and gene therapies unit at Novartis AG (NYSE:NVS; SIX:NOVN), which the pharma dissolved in August to integrate into its reorganized innovative medicines structure (see BioCentury Extra, Aug. 31).
Tmunity, co-founded by University of Pennsylvania immunotherapy professor Carl June, is developing T cell receptor (TCR) engineered T cells, Treg cells, and universal engineered T cell platforms that control T cell activation and direction in vivo. The company also is developing technologies to activate, expand and genetically engineer T cells from peripheral blood, cord blood and tumors (see BioCentury Extra, Jan. 13).
The closure of Novartis' cell and gene therapies unit has not slowed development of its lead cell therapy candidate. This week, the pharma said it plans to submit a BLA in early 2017 for CTL019 to treat pediatric relapsed or refractory B cell ALL. The therapy comprises autologous T cells loaded with a lentiviral vector expressing CART-19, which consists of a cancer antigen-binding domain targeting CD19 linked to CD3zeta/CD137 immunostimulatory domains (see BioCentury Extra, Dec. 5).
Voyager Therapeutics Inc. (NASDAQ:VYGR) gained $5.52 (40%) to $19.25 in early after-hours trading Wednesday when it announced interim results from a Phase Ib study of Parkinson's Disease gene therapy VY-AADC01. The data showed the higher of two tested doses increased biomarker activity and led to improvements on a disease severity scale in patients with advanced PD. Subjects receiving the higher dose also were able to reduce use of daily medications.
A five-patient cohort receiving the high dose had 56% greater activity of dopa decarboxylase (DDC; AADC) compared to baseline and were able to reduce intake of daily PD medications, including levodopa, by 34% after six months. The cohort also had a 56% improvement in Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) on medication at six months, with the effect sustained at 12 months.
Treatment resulted in a 20% increase in self-reported "on" time without dyskinesia from baseline to six months, and 43% improvement at 12 months. "Off" time with dyskinesia decreased 27% at six months, and 48% at 12 months.
Results were less pronounced in a lower-dose cohort, where patients had a 13% increase in DDC enzyme activity and 21% worsening in UPDRS-III scores at six months that was sustained at 12 months. "On" time decreased 3% at six months, but increased 16% from baseline at 12 months. Off-time with dyskinesia decreased 16% at six months and 27% at 12 months. The group reduced PD medication use by 14%.
The dose escalation study evaluated 10 patients at six months who received either 7.5x10^11 or 1.5x10^12 vector genomes. All five patients from the lower dose cohort were evaluable at 12 months, as were three patients from the high dose group.
Voyager said VY-AADC01 was well-tolerated, with two serious adverse events in one patient that were not related to the vector. It expects to report data in mid-2017 from a 4.5x10^12 vector genome dose cohort, and begin a placebo-controlled trial of the candidate in 4Q17.
VY-AADC01 is an adeno-associated virus (AAV) serotype 2 capsid and a cytomegalovirus promoter designed to deliver the DDC gene directly into the putamen. The Genzyme Corp. unit of Sanofi (Euronext:SAN; NYSE:SNY, Paris, France) has an exclusive option to obtain ex-U.S. rights to develop and commercialize Voyager's gene therapies for CNS diseases, including VY-AADC01 (see BioCentury Extra, Feb. 11, 2015).
Voyager released the results after market close. It lost $0.27 to $13.73 on Wednesday.
Veliparib (ABT-888) from AbbVie Inc. (NYSE:ABBV) missed the primary endpoint of a Phase II trial to treat patients with recurrent or metastatic breast cancer with BRCA1 or BRCA2 mutations, according to two abstracts posted on the web site of the San Antonio Breast Cancer Symposium (SABCS). The abstracts showed combinations including the oral PARP inhibitor failed to significantly improve progression-free survival (PFS) vs. placebo.
One abstract showed that veliparib plus carboplatin and paclitaxel led to PFS of 14.1 vs. 12.3 months for placebo plus carboplatin and paclitaxel (p=0.231). The veliparib combination also failed to significantly improve overall survival (OS); however, it did significantly improve overall response rate (ORR). OS and ORR were secondary endpoints.
A separate abstract showed veliparib plus temozolomide was inferior to placebo plus carboplatin and paclitaxel in improving PFS, OS and ORR. Data from that arm of the study are to be presented on Friday at SABCS.
The American Association for Cancer Research said the trial's size was "not sufficient to power the study to detect nondramatic improvements" in PFS, but added that the Phase III BROCADE 3 trial could "provide more definitive answers." BROCADE 3, which is now recruiting participants, is evaluating veliparib plus carboplatin and paclitaxel to treat HER2-negative metastatic or advanced unresectable BRCA-associated breast cancer.
Veliparib graduated from the adaptive Phase II I-SPY 2 trial, which studied the drug in triple-negative breast cancer patients (see BioCentury Extra, July 7).
Hanmi Pharmaceutical Co. Ltd. (KOSDAQ:128940) lost W37,500 (11%) to W311,000 on Wednesday as investors digested news that enrollment had been suspended in a Phase I trial of JNJ-64565111 (HM12525A) to treat Type II diabetes, according to an update on the study's ClinicalTrials.gov entry. The Janssen Biotech Inc. unit of Johnson & Johnson (NYSE:JNJ), which shares rights to the candidate with Hanmi, did not respond to inquiries about the suspension.
In November 2015, J&J obtained exclusive rights outside China and Korea to JNJ-64565111 from Hanmi under a deal covering oxyntomodulin-based therapies. Hanmi received $105 million up front in the deal, and is eligible for up to $810 million in milestones, plus tiered double-digit royalties (see BioCentury, Feb. 8).
JNJ-64565111 is a long-acting dual agonist of glucagon-like peptide-1 receptor (GLP-1R; GLP1R) and glucagon receptor (GCGR).
Immuno-oncology company TCR2 Therapeutics Inc. (Cambridge, Mass.) raised $44.5 million in a series A round led by MPM Capital and F2 Ventures.
The company plans to develop T cell therapies based on its T cell receptor (TCR) fusion construct (TRuC) platform. According to the company, the technology is designed to reprogram the TCR complex to recognize specific tumor antigens, and aims to apply its approch to solid as well as hematological cancers.
bluebird bio Inc. (NASDAQ:BLUE) and NeuroDerm Ltd. (NASDAQ:NDRM) each priced follow-on offerings, raising a combined $325 million.
bluebird raised $250 million through the sale of 3.3 million shares at $76 in a deal underwritten by Goldman Sachs, BofA Merrill Lynch, Cowen, Wells Fargo and Wedbush PacGrow. The price was a 4% discount to bluebird's close of $78.95 on Tuesday, before the offering was announced after market hours. bluebird slipped $8.45 (11%) to $70.50 on Wednesday.
On Nov. 30, bluebird gained 14% after it reported data from a Phase I trial showing that bb2121 led to an overall response rate of 78% in patients with multiple myeloma. The company shares rights with Celgene Corp. (NASDAQ:CELG) to bb2121, which comprises autologous T cells transduced ex vivo with an anti-BCMA02 chimeric antigen receptor (CAR) lentiviral vector targeting BCMA (see BioCentury Extra, Nov. 30).
NeuroDerm Ltd. (NASDAQ:NDRM) raised $75 million through the sale of 4 million shares at $18.75. Jefferies, Cowen, Raymond James and Roth Capital Partners were underwriters. The price was a 2% discount to the company's close of $19.15 on Tuesday, before the offering was announced after market hours. NeuroDerm lost $0.40 to $18.75 on Wednesday.
On Monday, NeuroDerm added 26% after revealing a new, shorter regulatory path in the U.S. for ND0612 to treat Parkinson's disease. The candidate delivers liquid levodopa/carbidopa continuously via a subcutaneous belt pump (see BioCentury Extra, Dec. 5).
Nordic Nanovector ASA (OSE:NANO) raised NOK498.7 million ($59.2 million) through the sale of 4.4 million shares at NOK114 in a private placement. DNB Markets, Jefferies and ABG Sundal Collier were underwriters.
Nordic Nanovector intends to use the funds for a planned Phase II study of Betalutin plus Rituxan rituximab to treat non-Hodgkin's lymphoma (NHL) and a Phase I study of an antibody-radionuclide conjugate targeting CD37. Betalutin is a lutetium-177 radiopharmaceutical conjugated to the anti-CD37 mAb lilotomab.
Nordic Nanovector proposed the offering after market hours on Tuesday, and slipped NOK3 to NOK117.50 on Wednesday.
In a new report describing its outlook for pharmaceutical spending, Quintiles IMS Holdings Inc. (NYSE:Q) said it expects both list and net prices of U.S. drugs to grow more slowly in the next five years than in recent years. It predicted an 8-11% annual increase in invoice prices for branded pharmaceuticals in the U.S. through 2021, down from 12-13% from 2011-14. It estimated annual net price increases of 2-5%, compared with increases of 4.9-9.1% from 2011-14.
The report said drug pricing, specifically the difference between gross and net prices, will be a key issue for the incoming Trump administration.
President-elect Donald Trump's transition team has two candidates on the short list for FDA commissioner, a source on the team told BioCentury. In addition to Scott Gottlieb, a resident scholar at the American Enterprise Institute who previously has been tipped for the job, the team is considering Jim O'Neill, a managing director at Mithril Capital. That firm was co-founded by Peter Thiel, a Silicon Valley entrepreneur who was an early backer of Trump's presidential campaign.
Gottlieb, a practicing physician, is a former FDA deputy commissioner for medical and scientific affairs. He is also a venture partner at New Enterprise Associates, and is an advisor or board member for at least four medical product companies and one patient group (see BioCentury, Nov. 14, 2016).
O'Neill would be a sharp departure from a tradition, dating to 1954, of appointing a physician or Ph.D. scientist to lead FDA. He holds a B.A. and master's degree in humanities from Yale University and the University of Chicago, respectively, and started his government career in 2001 as a speech writer for the Department of Education. O'Neill joined HHS as a senior advisor to the Deputy Secretary in 2005, and served as Principal Associate Deputy Secretary from November 2007 to October 2008.
O'Neill's ideas about drug development and regulation fall far outside the mainstream. "We should reform FDA so that it is approving drugs after their sponsors have demonstrated safety, and let people start using them at their own risk," he said in an August 2014 speech. "Let's prove efficacy after they've been legalized."
O'Neill also took credit for killing efforts by FDA to regulate in vitro diagnostic multivariate index assays during his tenure at HHS under the George W. Bush administration.
O'Neill is on the board of directors of the SENS Research Foundation. The non-profit organization promotes research into "rejuvenation biotechnologies," which it defines as "targeted therapies that apply the principles of regenerative medicine to the entire scope of the damage of aging." In the 2014 speech, O'Neill predicted that rejuvenation biotechnology could lead to human immortality within 40 years.
On Wednesday, the U.S. Senate passed the 21st Century Cures Act by a 94-5 vote. President Obama has endorsed the bill enthusiastically, and is expected to sign it soon.
The result of two years of deliberations and debate, the bill provides NIH with $4.8 billion in additional funding earmarked for the Cancer Moonshot, Precision Medicine, and Brain Research Through Advancing Innovative Neurotechnologies initiatives. It also creates a new approval pathway for antibiotics intended to target drug-resistant and emerging infections, establishes a framework for FDA to use real-world evidence for some regulatory decisions, and provides a legal foundation for the agency's patient-focused drug development initiative (see BioCentury, Dec. 5).
The Amyloidosis Research Consortium said it submitted draft guidance to FDA addressing drug development and clinical trial design for amyloid light chain (AL) amyloidosis. The patient group met with FDA, industry stakeholders and disease experts last year seeking a consensus on developing therapies for systemic amyloidoses (see BioCentury, Dec. 7, 2015).
ARC's guidance suggested clinical trial designs that account for the impaired cardiac and renal function in AL amyloidosis patients, and include broad patient populations with few eligibility restrictions. The guidance also encouraged using free light chains (FLC) or N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements as surrogate endpoints, rather than evaluating overall survival.
The advocacy group modeled its guidance on draft guidance submitted to FDA in June 2014 by Parent Project Muscular Dystrophy (PPMD) and a coalition of stakeholders on the development of drug candidates for Duchenne muscular dystrophy (DMD). FDA issued its draft guidance for DMD in June 2015 (see BioCentury, June 15, 2015).
ARC plans to craft a separate guidance for transthyretin (TTR)-mediated amyloidosis (ATTR). The group also submitted a Voice of the Patient report to FDA in June (see BioCentury Extra, June 7).
The Foundation for the National Institutes of Health (FNIH) released its framework outlining basic evidence required for biomarker qualification. The framework is designed to provide predictable and specific regulatory criteria, and was produced through collaboration among FNIH, FDA, NIH, the Critical Path Institute (C-Path), PhRMA and industry stakeholders.
The framework outlines a process for developers to describe the clinical need for a biomarker and context for its use, along with its potential risks and benefits, in order to determine evidentiary criteria required for validation. It outlines expectations for assay validation, knowledge of molecular mechanisms that underlie biomarker performance, and biomarker specificity that can be used as evidentiary criteria. The framework also encourages flexibility in adjusting biomarker use as its supporting data matures.
FNIH said the document should inform FDA's development of industry guidance on biomarker qualification, which is one key to conducting shorter, less expensive clinical trials (see BioCentury, Sept. 5).
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