Regulus Therapeutics Inc. (NASDAQ:RGLS) said FDA placed a full clinical hold on RG-101 after the company reported a second case of jaundice, a severe adverse event (SAE), in an ongoing Phase I study to treat chronic HCV. Regulus fell $2.76 (55%) to $2.25 in early after-hours trading on Monday after reporting the news.
In the new case, the patient experienced a jaundice event 117 days after receiving a single dose of RG-101. Regulus acknowledged the first case in April, when it reported updated interim data from a Phase II trial of the HCV therapy. The first patient developed jaundice 21 days after completion of therapy, which included a single dose of RG-101 followed by 28 days of treatment with Daklinza daclatasvir and a second dose of RG-101 on day 29 (see BioCentury Extra, April 15).
On a conference call Monday, CEO Paul Grint said both patients had diabetes and experienced elevations in bilirubin but not other liver enzymes. Grint said the study's investigator believed the event was unlikely to be treatment-related.
Grint said Regulus expects to receive official correspondence from FDA within 30 days, after which the company intends to evaluate options to lift the hold. It said the hold will not affect any ongoing studies of RG-101, all of which have completed dosing.
RG-101 is a GalNAc-conjugated antagonist targeting miR-122. Bristol-Myers Squibb Co. markets Daklinza, a selective HCV NS5A protein inhibitor.
Regulus lost $0.28 to $5.01 on Monday. It announced the news after market close.
Advanced Accelerator Applications S. A. (NASDAQ:AAAP) said FDA accepted and granted Priority Review to an NDA for Lutathera (177Lu-DOTA0-Tyr3-octreotate) to treat gastroenteropancreatic neuroendocrine tumors (GEP-NETS). Its PDUFA date is Dec. 28.
Last September, Advanced Accelerator said Lutathera significantly improved progression-free survival (PFS) compared with a double dose of Sandostatin LAR Depot octreotide acetate in the Phase III NETTER-1 trial to treat midgut neuroendocrine tumors (see BioCentury Extra, Sept. 16, 2015).
Lutathera is a radiolabeled somatostatin analog that targets somatostatin receptors. Advanced Accelerator has rights to radiolabeled peptide technology from Covidien plc (NYSE:COV).
Advanced Accelerator slipped $0.26 to $28.17 on Monday.
Puma Biotechnology Inc. (NYSE:PBYI) submitted an MAA to EMA for oral neratinib (PB272) as an extended adjuvant treatment for HER2-positive early stage breast cancer previously treated with Herceptin trastuzumab from the Genentech Inc. unit of Roche (SIX:ROG; OTCQX:RHHBY).
The company reiterated that it expects to submit an NDA to FDA mid-year for the oral inhibitor of HER1, HER2 and HER4 kinases. On March 29, Puma said FDA had requested that it rewrite clinical sections of the application, delaying its U.S. submission. It had hoped to submit the application in 1Q16 (see BioCentury Extra, March 29).
Puma has exclusive, worldwide rights to neratinib from Pfizer Inc. (NYSE:PFE).
Puma dipped $2.82 to $27.80 on Monday.
Sanofi (Euronext:SAN; NYSE:SNY) is to exchange its Merial animal health unit for the consumer healthcare business of Boehringer Ingelheim GmbH (Ingelheim, Germany) in an asset swap. The deal excludes Boehringer's consumer healthcare business in China.
The companies said Merial's enterprise value is EUR 11.4 billion ($12.6 billion), while Boehringer's consumer healthcare business has an enterprise value of EUR 6.7 billion ($7.4 billion). Boehringer will pay Sanofi EUR 4.7 billion ($5.2 billion) in cash to account for the difference.
The companies, which began negotiating the deal in December, expect the deal to close by year end.
Some investors have suggested Sanofi should pare down or spin off its lower-margin businesses (see BioCentury, Nov. 11, 2014).
Uni-Bio Science Group Ltd. (HKSE:690) said it granted exclusive commercialization rights in China to ophthalmology treatment GeneSoft to the China Resources Zizhu Pharmaceutical Co. Ltd. subsidiary of China Resource Pharmaceuticals Group (Beijing, China). Zizhu will have rights to GeneSoft for five years, with an option to renew for an additional five years.
GeneSoft, an ophthalmic solution containing a derivative of recombinant human epidermal growth factor, is approved in China to treat corneal defects and wounds. Uni-Bio said Zizhu will distribute the treatment through its existing hospital network. Financial terms were not disclosed.
GW Pharmaceuticals plc (LSE:GWP; NASDAQ:GWPH) said anticonvulsive therapy Epidiolex cannabidiol significantly reduced the monthly frequency of drop seizures in patients with Lennox-Gastaut syndrome (LGS), meeting the primary endpoint of a Phase III study. GW gained 60.50p (12%) to 566.50p in London on Monday, and rose $5.18 to $88.49 on NASDAQ.
Dosed as an adjunct therapy alongside anti-epileptic regimens, 20 mg/kg per day of Epidiolex reduced the monthly frequency of drop seizures by 44% during the study's 14-week treatment period vs. 22% for placebo (p=0.0135). The 171-patient trial enrolled patients aged 2-55 whose disease was uncontrolled on at least one anti-epileptic drug. Their median monthly drop seizure frequency was 74 at baseline.
Adverse events included diarrhea, somnolence, decreased appetite, pyrexia and vomiting. One death in the Epidiolex group was deemed unrelated to treatment.
Next quarter, GW expects top-line data from a second Phase III study of Epidiolex to treat LGS. In March, GW said Epidiolex met the primary endpoint of significantly reducing convulsive seizures vs. placebo in a Phase III trial to treat Dravet syndrome, another rare form of epilepsy. GW's valuation has more than doubled since its shares closed at 216.50p in London and $38.46 on NASDAQ on March 11, before the Dravet syndrome results were announced (see BioCentury Extra, March 14).
The company plans to submit an NDA for Epidiolex in 1H17. It is an oral liquid formulation of cannabidiol, a phytocannabinoid found in Cannabis sativa.
The therapy has Orphan Drug designations from FDA and EMA, and Fast Track designation from FDA, to treat Dravet syndrome. It also has Orphan Drug designation from FDA to treat LGS.
The Medicines Co. (NASDAQ:MDCO) said Carbavance meropenem/vaborbactam was non-inferior to tazobactam/piperacillin on both the FDA- and EMA-specified primary endpoints in the 550-patient, Phase III TANGO 1 trial to treat complicated urinary tract infection. The company plans to submit regulatory applications to EMA and FDA next year.
In TANGO 1's microbiologic modified intent-to-treat (mITT) population, Carbavance led to a clinical outcome rate of 98.4% vs. 94% for tazobactam piperacillin, meeting the FDA-specified primary endpoint of non-inferiority. The Medicines Co. said Carbavance also showed superiority to its comparator on the same endpoint, which was defined as cure or improvement and eradication at the end of IV treatment. Patients received either therapy every eight hours for up to 10 days.
Carbavance met both EMA-specified endpoints, showing non-inferiority on each. The endpoints were the proportion of patients who achieved microbiologic eradication after 15-19 days in TANGO 1's microbiologic mITT population (66.7% for Carbavance vs. 57.7% for tazobactam/piperacillin) and microbiologic evaluable population (66.3% for Carbavance vs. 60.4% for tazobactam/piperacillin).
The Medicines Co. said drug-related treatment-emergent adverse events occurred with similar frequency between the two groups. There were two deaths in each treatment group.
The company plans to present detailed TANGO 1 data at an upcoming conference.
The Medicines Co. is developing Carbavance under a contract with HHS's Biomedical Advanced Research and Development Authority (BARDA). The company also is conducting the ongoing Phase III TANGO 2 study comparing Carbavance vs. best available therapy in patients with carbapenem-resistant Enterobacteriaceae (CRE) infections.
Carbavance combines vaborbactam, a boron-containing beta lactamase (LACTB) inhibitor; and meropenem, a carbapenem antibiotic. It has Qualified Infectious Disease Product (QIDP) designation from FDA.
The Medicines Co. closed up $0.02 to $33.28 on Monday.
Allergy Therapeutics plc (LSE:AGY) lost 3.50p (15%) to 20p on Monday after it said it would need to conduct another dose-ranging study of grass allergy therapy GrassMATAMPL next year before beginning a U.S. Phase III trial. The company said it failed to determine a recommended dose based on a Phase II dose-ranging study.
GrassMATAMPL is an ultra-short course allergen-specific immunotherapy comprising modified allergens, microcrystalline tyrosine (MCT) and monophosphoryl lipid A (MPL). The company markets the product in Europe as Pollinex Quattro Grass.
The setback is the second in as many weeks for a British allergy company. Last Monday, Circassia Pharmaceuticals plc (LSE:CIR) fell 66% and shed L510.8 million ($745.2 million) in market cap after its cat allergy therapy Cat-SPIRE missed the primary endpoint in a Phase III study (see BioCentury, June 27).
Biotech stocks sank again Monday as global markets continued to react to news of last week's Brexit vote. The BioCentury 100 lost 144.22 (3.2%) to 4,408.07, with decliners outpacing gainers 95-5. The close was the index's lowest since Feb. 11, when it ended the day at 4,374.01. The index is off 8.1% since its June 23 close of 4,798.77, before polls closed for the Brexit vote.
The NASDAQ Biotechnology Index (NBI) dipped 3.1% on Monday, while the NYSE Arca Biotechnology Index (BTK) lost 3.9% and the iShares NASDAQ Biotechnology ETF (IBB) shed 3%.
In a blow to the diagnostics industry, the U.S. Supreme Court declined to review a lower court's decision that had invalidated a patent owned by Sequenom Inc. (NASDAQ:SQNM) covering a prenatal diagnostic test. The company had asked the court to review the case and the patent eligibility criteria established in its 2012 Mayo Collaborative Services v. Prometheus Laboratories Inc. decision, which the lower court had used as rationale to invalidate Sequenom's patent. Multiple life sciences companies and industry groups had filed briefs supporting Sequenom.
In 2013, the U.S. District Court for the Northern District of California ruled that Sequenom's U.S. Patent No. 6,258,450 was invalid because its claims did not add enough to a natural phenomenon to make them patent eligible. The patent covered prenatal diagnosis with nucleic acid analysis used in its MaterniT21 Plus laboratory-developed test. Sequenom had filed a suit alleging that Ariosa Diagnostics Inc. (San Jose, Calif.) infringed the patent.
The district court's decision was upheld in 2015 by the U.S Court of Appeals for the Federal Circuit, which cited the Mayo decision in its ruling. In Mayo, the Supreme Court found that a correlation between blood levels of a metabolite and optimum dosing of a drug were a law of nature and could not be patented (see BioCentury, March 26, 2012).
PhRMA declined to comment on the Supreme Court's decision. In an amicus brief submitted to the Supreme Court in support of Sequenom, the trade group said the prior ruling "risks prohibition of patents on innovative, meritorious process inventions, such as biomarker-based prognostic and diagnostic inventions."
Sequenom fell $0.18 (16%) to $0.95 on Monday.
A draft of the U.S. Democratic Party platform approved Saturday includes calls for reducing prescription drug prices by giving HHS power to negotiate Medicare drug prices, allowing drug importation, and prohibiting "pay-for-delay" deals that delay marketing of generic drugs, according to a summary released by the Democratic National Committee.
The Platform Committee is to vote on a final version at a meeting July 8-9, after which the platform will be submitted for ratification at the Democratic National Convention July 25-28. The prescription drug provisions in the draft platform are consistent with Hillary Clinton's proposals for lowering prescription drug costs.
The 2008 Democratic platform also contained pledges to negotiate Medicare drug prices and end pay for delay, but the Obama administration has been unable to move these measures through Congress.
Individuals employed by pharmaceutical and health products companies have donated $3 million to the Clinton campaign and associated political action committees, according to Federal Election Commission data compiled by the Center for Responsive Politics. The Donald J. Trump campaign has received donations of about $6,000 from pharma and health products company employees.
HHS's Biomedical Advanced Research and Development Authority (BARDA) will provide Emergent BioSolutions Inc. (NYSE:EBS) at least $17.9 million over the next 30 months to develop and manufacture three cGMP lots of a Zika vaccine for use in a Phase I study.
Emergent, which is one of HHS's Centers for Innovation in Advanced Development and Manufacturing, will use vaccine technology similar to that used in vaccines for similar viruses including dengue.
Anthony Fauci, director of NIH's National Institute of Allergy and Infectious Diseases (NIAID), said earlier this year that at least one Zika vaccine candidate could be administered in large-scale trials in 2017 (see BioCentury, Feb. 15).
Last week, Inovio Pharmaceuticals Inc. (NASDAQ:INO) and GeneOne Life Science Inc. (KSE:011000) said they plan to start a Phase I study within weeks of GLS-5700, their vaccine to prevent Zika virus infection.
Legislation appropriating federal funding to respond to the Zika threat, including support for vaccine development, is stalled in Congress.
Emergent slipped $2.10 to $27.24 on Monday.
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