Alkermes plc (NASDAQ:ALKS) gained $19.47 (45%) to $62.98 in early after-hours trading Thursday after it said the higher of two doses of ALKS 5461 met the primary endpoint of the FORWARD-5 trial as an adjunctive therapy for major depressive disorder in patients who do not respond adequately to standard antidepressants. Alkermes hopes to meet with FDA to discuss a regulatory submission strategy for the compound, which combines buprenorphine with samidorphan (ALKS 33), a mu opioid receptor (OPRM1; MOR) antagonist.
In two previous Phase III MDD studies, ALKS 5461 missed the primary endpoint of improving Montgomery-Asberg Depression Rating Scale (MADRS) scores from baseline vs. placebo. Alkermes shares sank 44% on Jan. 21 after the company disclosed those results. They had closed at $60.42 on Jan. 20 (see BioCentury Extra, Jan. 21).
In FORWARD-5, the higher dose significantly reduced depression scores vs. placebo, as measured by six-item MADRS (MADRS-6) scores (p=0.018). Alkermes said a lower dose led to symptomatic improvements, but "did not separate significantly" vs. placebo.
On a conference call Thursday, EVP of R&D and CMO Elliot Ehrich said Alkermes used MADRS-6 as the FORWARD-5's primary endpoint because the scale "may provide a more specific measure of antidepressant activity." Chairman and CEO Richard Pops said MADRS-6 has not previously been used as a primary endpoint to support regulatory approval. Ehrich also said the company did not receive feedback on its statistical plan from FDA before the study was unblinded.
ALKS 5461 has Fast Track designation from FDA to treat refractory MDD.
Ablynx N.V. (Euronext:ABLX) fell EUR 1.41 (13%) to EUR 9.50 after AbbVie Inc. (NYSE:ABBV) declined to exercise its option to license vobarilizumab (ALX-0061) to treat rheumatoid arthritis. Ablynx said it is seeking a new partner for vobarilizumab and beginning preparations for a Phase III study of the subcutaneous nanobody against IL-6 receptor (CD126), which it expects to begin by YE17.
AbbVie spokesperson Raquel Powers told BioCentury the candidate "did not meet AbbVie's criteria for moving forward with full development in RA." AbbVie paid $175 million up front in 2013 for options to vobarilizumab in RA and systemic lupus erythematosus (SLE), for which AbbVie still has an option (see BioCentury Extra, Sept. 23, 2013).
Ablynx gained 12% on July 7 after it reported data comparing three dosing regimens of vobarilizumab to more frequently dosed Actemra tocilizumab to treat moderately to severely active RA. The study was not powered to show significance vs. Actemra (see BioCentury Extra, July 7).
Data released in August from a second Phase IIb study showed vobarilizumab plus methotrexate missed the primary endpoint of significantly improving ACR20 rates at week 12 vs. placebo plus methotrexate. On Thursday, Ablynx attributed the miss to an "unusually high placebo response," and said the candidate still showed an effect on other clinically relevant endpoints.
CEO Edwin Moses told a conference call Thursday that the company was open to "a whole range" of partnering opportunities, including co-financing a Phase III study in RA. He said Ablynx expects results in 1H18 from a Phase II study of vobarilizumab to treat SLE.
The Genentech unit of Roche (SIX:ROG; OTCQX:RHHBY) and Chugai Pharmaceutical Co. Ltd. (Tokyo:4519) market Actemra, a humanized mAb against CD126.
Gilead Sciences Inc. (NASDAQ:GILD) reported top-line data from four Phase III trials of pan-genotypic HCV combination therapy sofosbuvir/velpatasvir/voxilaprevir, including sustained viral response data in patients previously treated with direct-acting antivirals (DAAs) and patients with cirrhosis. The company plans to submit an NDA for the combination next quarter, and said it could be the first approved once-daily salvage therapy following DAAs.
In the 333-patient POLARIS-4 study, Gilead said a 12-week course of the triple combo led to an SVR12 in 97% of patients vs. 90% for Gilead's Epclusa sofosbuvir/velpatasvir. The study evaluated patients with HCV genotype 1-4 infection, 46% of whom had cirrhosis, who had previously received a DAA such as Sovaldi sofosbuvir, but not an NS5A inhibitor.
In the 415-patient POLARIS-1 study, a 12-week course of the triple combo produced an SVR12 in 96% of patients vs. zero for placebo. That study included NS5A inhibitor-experienced patients with HCV genotype 1-6 infection, 41% of whom were cirrhotic.
In POLARIS-3, among 219 DAA-naive cirrhotic patients with genotype 3 infection, the triple combo produced an SVR12 in 96% of patients after eight weeks of treatment. Compared with a 12-week course of Epclusa, an eight-week course of the combo failed to show non-inferiority at improving SVR12 rates in POLARIS-2, missing that study's primary endpoint. POLARIS-2 tested the therapies in DAA-naive patients with genotype 1-6 infection, 18% of whom had cirrhosis.
The POLARIS program evaluated a fixed-dose combination of Sovaldi, a nucleotide analog HCV NS5B polymerase inhibitor; velpatasvir, a pan-genotypic HCV protein inhibitor; and voxilaprevir (GS-9857), a pan-genotypic HCV NS3/NS4A protease inhibitor. Gilead is to present full study results next month at The Liver Meeting in Boston.
In June, FDA approved Epclusa, a fixed-dose combination of Sovaldi and velpatasvir. It was the first regimen approved to treat all six HCV genotypes (see BioCentury Extra, June 28).
Rigel Pharmaceuticals Inc. (NASDAQ:RIGL) dropped $0.49 (15%) to $2.73 on Thursday after fostamatinib disodium (formerly R788) missed the primary endpoint of the FIT 2 trial, the second of two Phase III studies of the candidate to treat idiopathic thrombocytopenic purpura. Fostamatinib failed to significantly improve stable platelet response rates vs. placebo, as defined by platelet counts of at least 50,000/uL of blood on at least four of the last six qualifying blood draws.
In the 74-patient study, fostamatinib led to a response rate of 18% vs. 4% for placebo (p=0.152). Rigel attributed the miss to a single placebo responder.
Rigel said the response rate in FIT 2 was equivalent to that seen in the Phase III FIT 1 study, in which fostamatinib met the primary endpoint. The company said that pooled data from the two studies showed a significant improvement vs. placebo (18% vs. 2% response rate, p=0.007) (see BioCentury Extra, Aug. 30).
Rigel plans to discuss the studies with FDA. It is also evaluating partnership opportunities for the oral spleen tyrosine kinase (SYK) inhibitor, including an ex-U.S. deal.
The biotech said it had about $85.3 million in cash at Sept. 30, enough to fund operations through 2017.
Gilead Sciences Inc. (NASDAQ:GILD) said anti-fibrotic activity shown in a Phase II study of selonsertib (GS-4997) to treat non-alcoholic steatohepatitis warrants advancement of the compound into Phase III testing in the indication.
Among 67 evaluable patients in the open-label Phase II trial, high and low doses of selonsertib plus simtuzumab (GS-6624) led to fibrosis improvements at 24 weeks of at least one stage from baseline in 43% and 30% of patients, respectively, compared with 20% for simtuzumab alone. Fibrosis stage was determined according to the NASH Clinical Research Network (CRN) classification.
The trial evaluated 18 mg and 6 mg daily doses of selonsertib, an apoptosis signal-regulating kinase 1 (ASK1; MAP3K5) inhibitor, in patients with NASH and moderate to severe liver fibrosis. Gilead said no differences were observed between treatment groups evaluating selonsertib as monotherapy vs. the compound in combination with simtuzumab, a humanized mAb against lysyl oxidase-like 2 (LOXL2).
Gilead also said selonsertib missed the primary endpoints of Phase II studies to treat pulmonary arterial hypertension (PAH) and diabetic kidney disease (DKD). It does not plan to conduct Phase III studies in either indication.
Gilead added $0.97 to $74.31 on Thursday. The company is also developing two other NASH candidates: GS-0976, which is an acetyl-coenzyme A carboxylase (ACAC; ACC) inhibitor; and GS-9674, which is a farnesoid X receptor (FXR; NR1H4) agonist.
Theravance Biopharma Inc. (NASDAQ:TBPH) and Mylan N.V. (NASDAQ:MYL) reported that revefenacin (TD-4208) met the primary endpoints in two replicate Phase III trials to treat chronic obstructive pulmonary disease. Both of the studies' doses of revefenacin significantly improved trough forced expiratory volume in one second (FEV1) vs. placebo. The trials enrolled a total of more than 1,250 patients with moderate to very severe COPD.
The companies said they are developing the long-acting muscarinic antagonist (LAMA) to be the first once-daily, nebulized bronchodilator for COPD. Theravance expects to complete an ongoing Phase III safety trial next year, and hopes to submit an NDA to FDA by YE17.
Mylan has rights to nebulized revefenacin outside the U.S. and China under a 2015 deal (see BioCentury Extra, Feb. 2, 2015).
Theravance gained $0.79 to $32.80 on Thursday.
Neurobehavioral newco BlackThorn Therapeutics Inc. (South San Francisco, Calif.) raised $40 million in a series A round led by Arch Venture Partners. The Johnson & Johnson Innovation-JJDC venture arm of Johnson & Johnson (NYSE:JNJ), Altitude Life Science Ventures, Mercury Fund and Alexandria Real Estate Equities also participated, as did an undisclosed crossover fund.
BlackThorn's lead program, opioid related nociceptin receptor 1 (OPRL1; NOPR) antagonist BTRX-246040 (formerly LY-2940094), is due to enter Phase II testing next year for mood disorders. The start-up obtained exclusive, worldwide rights to the asset from Eli Lilly and Co. (NYSE:LLY) this year after the pharma shuttered its neuroscience program.
"Large pharma companies have fundamentally shut down their neuroscience groups," BlackThorn Executive Chairman Mark Corrigan told BioCentury, despite "an explosion of knowledge about neuroscience." Arch Managing Director Kristina Burow added that despite a "staggering, underreported" unmet need, pharmas' reduced investment has lessened competition in the sector.
Corrigan said the heterogeneity of patient populations has been a major obstacle in developing CNS treatments. Using its INFORM platform, BlackThorn plans to discover and development treatments targeted to specific subpopulations using emerging knowledge of the underlying biology of brain disorders.
INFORM is designed to link brain physiology to behavior by using functional imaging to target key brain regions that regulate behaviors of interest. It uses a collection of objective endpoints to quantify emotion, behavior and cognition.
BlackThorn plans to use INFORM to design smaller, more efficient clinical trials that selectively enroll patients who are most likely to benefit from its products.
The start-up also hopes to begin Phase I testing next year of a compound targeting the kappa-opioid receptor system. It has two additional programs in discovery.
Burow and JJDC's Asish Xavier took seats on BlackThorn's board.
Puma Biotechnology Inc. (NYSE:PBYI) raised $150 million through the sale of 3.8 million shares at $40 per share in a follow-on underwritten by Citigroup, JPMorgan, Credit Suisse, BofA Merrill Lynch and Stifel. The company proposed the offering after market hours Tuesday, when its shares closed at $52.65. Puma sank $9.95 (19%) to $42.70 on Wednesday, then added $1.10 to $43.80 on Thursday.
Puma's oral neratinib (PB272) is under FDA and EMA review as an extended adjuvant treatment for HER2-positive early stage breast cancer previously treated with Herceptin trastuzumab. Neratinib is an oral inhibitor of HER1, HER2 and HER4 kinases.
Organ-on-chip company Emulate Inc. (Boston, Mass.) said it added $17 million to its series B round, bringing the round's total to $45 million. Undisclosed private individuals and institutional and non-institutional funds joined the round for the new close. Emulate announced the $28 million first close in March (see BioCentury Extra, March 28).
Also on Thursday, Emulate said it partnered with the Covance Inc. contract research unit of Laboratory Corp. of America Holdings (NYSE:LH) and the Lawrence J. Ellison Institute for Transformative Medicine at the University of Southern California. Emulate and LabCorp will work to improve preclinical drug evaluation and drug development, focusing initially on Emulate's Kidney-Chip to examine drug-transporter interactions. The USC collaboration concerns organ and disease models to predict responses to cancer treatments.
LabCorp was among Emulate's initial series B investors.
Emulate's Organ-Chips contain hollow channels lined by living cells and tissues that are exposed to continuous fluid flow and mechanical forces such as peristalsis or breathing. The chips can mimic normal organ physiology or model disease (see BioCentury Innovations, June 25, 2015).
Science and technology development firm PureTech Health plc (LSE:PRTC) hired Joseph Bolen as CSO. He was CSO at Moderna Therapeutics Inc. (Cambridge, Mass.).
On Thursday, EMA began providing open access to clinical reports for medicines approved in the EU as part of a transparency initiative. The agency said citizens, researchers and academics will have direct access to clinical trial reports submitted by application sponsors via an online database.