Meeting both expectations and concerns in the scientific community that the gene-editing technique CRISPR/Cas9 (CRISPR-associated protein 9) would be applied to human embryos, a group of Chinese researchers has published a study in the journal Protein & Cell testing the efficiency and limitations of the method on non-viable pre-blastocyst human embryos.
The study demonstrated that although the technique cleaved the target hemoglobin beta (HBB) gene, it worked with low efficiency, produced mosaic embryos -- embryos that contain mixtures of edited and unedited HBB genes -- and induced off-target cleavage at other sites on the genome. The authors concluded the technique is not yet safe for clinical applications.
But neither that nor the fact that the researchers used embryos incapable of implantation will quell fears the technology will be used to edit human germline cells before either its safety or ethical boundaries have been established.
Last month, a group of prominent scientists called for a conference to set guidelines for responsible use of CRISPR-based gene editing. Some have called for a complete moratorium on its use in human embryos on the grounds that manipulating the human germline crosses a moral line. Others believe the technique could one day address severe genetic disorders, but its use should be limited to research applications until it can be proven safe (see BioCentury Innovations, March 26).
Editas Medicine (Cambridge, Mass.), Caribou Biosciences Inc. (Berkeley, Calif.), Intellia Therapeutics LLC (Cambridge, Mass.) and CRISPR Therapeutics AG (Basel, Switzerland) were all founded within the last two years to develop CRISPR-based therapeutics. All four companies focus on gene editing in somatic cells, which does not carry through to future generations.
AbbVie Inc. (NYSE:ABBV) reported $231 million in global 1Q15 sales of HCV regimen Viekira Pak paritaprevir/ritonavir/ombitasvir/dasabuvir and maintained its forecast of a global annualized sales run rate of more than $3 billion for the drug by YE15.
On the company's earnings call, CFO William Chase said many U.S. contracts for Viekira begin this quarter and sales are expected to build through the remainder of the year. Chase also said the company has obtained reimbursement in global markets faster than anticipated, which may lead to more international sales than originally forecasted.
FDA accepted an NDA and granted Priority Review for AbbVie's two direct-acting antiviral (2-DAA) regimen of paritaprevir/ritonavir/ombitasvir plus ribavarin to treat HCV genotype 4. AbbVie said the regimen is the first all-oral, interferon-free therapy under review by FDA for HCV genotype 4. Partner Enanta Pharmaceuticals Inc. (NASDAQ:ENTA) is eligible to receive double-digit royalties on 45% of global sales of any 2-DAA HCV regimen form AbbVie containing paritaprevir.
AbbVie increased its 2015 non-GAAP EPS forecast to $4.10-$4.30 from $4.05-$4.25. It reported non-GAAP 1Q15 EPS of $0.94, beating consensus estimates by $0.09 and up 32% from $0.71 in 1Q14.
AbbVie dipped $0.27 to $64.25 on Thursday.
After closing its $16 billion asset swap with GlaxoSmithKline plc (LSE:GSK; NYSE:GSK), Novartis AG (NYSE:NVS; SIX:NOVN) said on its 1Q15 earnings call Thursday that it is seeking bolt-on acquisitions on the order of $2-$5 billion over the next 12-18 months to strengthen its pipeline.
David Epstein, division head of Novartis Pharmaceuticals, said on the call that the company expects to launch LCZ696 in 3Q15. The dual inhibitor of angiotensin II type 2 (AT2) receptor (ATGR2) and neutral endopeptidase (neprilysin; MME; NEP; CD10) is under Priority Review by FDA to treat heart failure with reduced ejection fraction.
Novartis reported $11.9 billion in net sales in 1Q15, down 7% from $12.8 billion in 1Q14 but up 3% using constant exchange rates. The company reported core EPS of $1.33, down from $1.35 in 1Q14 but up 11% using constant exchange rates.
Novartis gained $2.05 to $105.50 on NYSE on Thursday.
Juno Therapeutics Inc. (NASDAQ:JUNO) and the MedImmune LLC unit of AstraZeneca plc (LSE:AZN; NYSE:AZN) entered a non-exclusive collaboration to study a combination of MedImmune's PD-L1 inhibitor MEDI4736 and a Juno chimeric antigen receptor (CAR) T cell therapy directed against CD-19.
MedImmune spokesperson Susannah Budington told BioCentury the companies plan to begin a Phase Ib study of the combination this year to treat non-Hodgkin's lymphoma (NHL). The parties said they will fund the trial jointly, but did not release specific financial terms.
MedImmune and Juno did not specify which of Juno's therapies will be tested in the combination study. They also plan to explore a combination using a second, "next-generation" anti-CD19 from Juno.
Juno has three clinical candidates, all CAR T therapies against CD-19. It has tested JCAR014 in patients with NHL, but has said it does not plan to conduct registration trials of the candidate. Juno intends to begin a Phase I/II trial this year of JCAR017 to treat adults with relapsed refractory NHL. The company has studied the third candidate, JCAR015, to treat acute lymphoblastic leukemia (ALL).
Budington said anti-CD19 CAR T monotherapies have thus far led to longer-lasting responses in ALL than in NHL. She said the companies do not plan to investigate the combination in solid tumors.
MedImmune began a Phase III study in 2Q14 of MEDI4736 to treat non-small cell lung cancer (NSCLC), and has investigated the therapy alone and in combination to treat multiple solid tumors including head and neck cancer.
Juno was up $2 to $57.72 on Thursday.
Continuing a string of patent challenges, hedge fund manager Kyle Bass filed an inter partes review (IPR) challenging a patent held by Celgene Corp. (NASDAQ:CELG) covering Revlimid lenalidomide. Celgene markets the thalidomide analog to treat mantle cell lymphoma (MCL), multiple myeloma (MM) and myelodysplastic syndromes (MDS).
The Coalition for Affordable Drugs VI filed the IPR on Wednesday with the U.S. Patent and Trademark Office challenging U.S. Patent No. 6,045,501, which issued in 2000 and covers methods for preventing fetal exposure to tetragenic drugs. The IPR argues Celgene's claims are obvious, noting initial rejections by the U.S. Patent Office on those grounds.
The '501 patent is set to expire in 2018. There are 24 Orange Book-listed patents covering Revlimid, with the last expiring in 2028. U.S. sales of Revlimid were $797 million in 4Q14.
Coalition for Affordable Drugs VI is a subsidiary of Hayman Credes Master Fund, which is operated by Hayman Capital Management. Bass is the founder and chief investment officer of Hayman Capital.
Bass also is targeting patents for MS drugs Tecfidera dimethyl fumerate from Biogen Inc. (NASDAQ:BIIB) and Ampyra dalfampridine from Acorda Therapeutics Inc. (NASDAQ:ACOR); narcolepsy drug Xyrem sodium oxybate from Jazz Pharmaceuticals plc (NASDAQ:JAZZ); short bowel syndrome treatment Gattex teduglutide and ulcerative colitis (UC) drug Lialda mesalamine from Shire plc (LSE:SHP; NASDAQ:SHPG); and blood cancer drug Imbruvica ibrutinib from Pharmacyclics Inc. (NASDAQ:PCYC) (see BioCentury Extra, April 21).
Celgene gained $0.55 to $116.09 on Thursday.
U.K.-based not-for-profit MRC Technology partnered with New York University School of Medicine to develop antibodies against the university's targets to treat inflammatory osteolysis, a disease involving breakdown and resorption of bone.
Nadim Shohdy, director of drug discovery partnerships at NYU, would not disclose the targets but said they consist of an axon guidance molecule and its receptors. Shohdy said both partners will conduct research, but MRC will develop the antibodies. Each partner will fund its own research; the two will share royalties from any approved drugs emerging from the collaboration.
Once MRC and NYU have a clinical candidate in hand, the collaborators will look to partner it with a company rather than conduct clinical trials themselves, Shohdy said. He would not say when the partners expect to choose a clinical candidate.
Royalty play Ligand Pharmaceuticals Inc. (NASDAQ:LGND) said CFO Nishan de Silva resigned effective May 20. Melanie Herman, Ligand's director of accounting and chief accounting officer, will be interim CFO.
Renal therapeutic company Keryx Biopharmaceuticals Inc. (NASDAQ:KERX) named John Neylan CMO. Neylan was SVP of clinical development at Genzyme Corp.
Vaccine company CSL Ltd. (ASX:CSL) said CFO Gordon Naylor will lead its new global influenza vaccine business, with a planned launch in early 2016.
Bioinformatics company Medidata Solutions Inc. (NASDAQ:MDSO) named Rouven Bergmann CFO. He was CFO at SAP North America.
Cell therapy play Apceth GmbH & Co. KG named Ulrike Verzetnitsch chief technical officer. Verzetnitsch was head of the Signen, Germany, production unit for Takeda Pharmaceutical Co. Ltd. (Tokyo:4502).
Aerie Pharmaceuticals Inc. (NASDAQ:AERI) fell $23.01 (65%) to $12.38 in after hours trading Thursday after it said Rhopressa (AR-13324) missed the primary endpoint of the Phase III Rocket 1 trial to treat intraocular pressure in patients with glaucoma or ocular hypertension.
Rhopressa failed to show non-inferiority to adrenergic receptor beta (ADRB) blocker timolol in lowering IOP, the primary endpoint, in glaucoma patients with an IOP between 20 and 27 mmHg.
Aerie said the dual inhibitor of Rho kinase and the norepinephrine transporter was non-inferior to timolol in patients with IOP <26. On a conference call, company executives said they will consider meeting with FDA to discuss modifying the primary endpoint of the Phase III Rocket 2 study, from which it expects data in 3Q15, or conducting a new trial with a different endpoint.
Gilead Sciences Inc. (NASDAQ:GILD) reported efficacy data from a Phase II trial evaluating six- and four-week courses of a triple combination therapy to treat HCV genotype 1 infection. The combo includes approved HCV drug Sovaldi sofobuvir plus two investigational therapies: GS-9857, a pan-genotypic HCV NS3 protease inhibitor, and GS-5816, an oral pan-genotypic HCV NS5A inhibitor.
Among genotype 1 patients treated for six weeks, SVR12 rates were 93% for treatment-naive, non-cirrhotic patients (n=14/15); 87% for treatment-naive, cirrhotic patients (n=13/15); and 67% for patients who had previously failed treatment with two or more direct-acting antivirals (DAAs) (n=20/30).
Gilead said the four-week course led to a "sub-optimal" SVR12 rate of 27% (n=4/15).
The company reported no serious adverse events in the trial. The most common AEs were nausea, headache and fatigue.
Most HCV therapies are administered for 12-24 weeks. Gilead's Harvoni ledipasvir/sofosbuvir, which is approved in the U.S. and EU to treat HCV genotype 1 infection, can be administered as an eight-week course in some treatment-naive patients without cirrhosis.
Gilead also reported data on Thursday suggesting GS-9857 may be effective for multiple HCV genotypes. The company said GS-9857 monotherapy demonstrated similar antiviral potency against genotypes 1-6 in a preclinical study and reduced median HCV RNA levels by >3 log10 IU/mL in patients with genotypes 1-4 in a Phase I study.
Gilead said it has started additional Phase II trials testing the triple combo to treat multiple genotypes. The company did not respond to a request for details.
The company will present the data at the European Association for the Study of the Liver meeting in Vienna.
Gilead gained $1.03 to $105.21 on Thursday.
Cancer company Jounce Therapeutics Inc. (Cambridge, Mass.) raised $56 million in a series B round from Wellington Management, Redmile Group, Nextech Invest, Pharmstandard International, Cormorant Asset Management, Omega Funds, Casdin Capital, Foresite Capital and an undisclosed public investment fund.
Jounce plans to start clinical testing next year of its inducible T cell co-stimulator (ICOS) agonist antibody.
The company raised $47 million from Third Rock Ventures in its 2013 series A round (see BioCentury Extra, Feb. 14, 2014).
"Third Rock footed the full series A," Jounce CEO Richard Murray told BioCentury. "As fate would have it for us in pulling this B round together, we got oversubscribed so we thought it was wise to get a diverse investor base. We're happy with the investor base because we want to be here for the long haul and retain our products as we add value to them."
The WuXi NextCODE Genomics subsidiary of WuXi PharmaTech Inc. (NYSE:WX) partnered with DNAnexus Inc. (Mountain View, Calif.) and invested $15 million in the genome informatics company. The companies intend to create new products using WuXi NextCODE's genome analytics and DNAnexus' cloud-based technology platform.
WuXi NextCODE COO Hannes Smarason told BioCentury the company intends to launch a WuXi-branded cloud server in China for sequencing data, built on DNAnexus' platform.
WuXi PharmaTech acquired NextCODE Health in January, allowing it to create genomic and bioinformatic products for personalized medicine (see BioCentury, Feb. 2).
The Energy and Commerce Committee's health subcommittee will hold a hearing on April 30 to discuss 21st Century Cures legislation. FDA and NIH will testify at the hearing. Legislative text will be available in the coming days.
E&C Committee Republicans released a discussion draft of the bill in January that has not been supported by Democrats (see BioCentury, Feb. 9).
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