The Biotechnology Industry Organization believes that a Congressional Budget Office estimate of the cost of proposed patent reforms is based on faulty assumptions, BIO General Counsel Tom DiLenge told BioCentury.
The CBO has made a preliminary estimate that a request from BIO and the Pharmaceutical Research and Manufacturers of America to add language to pending patent reform bills that would exempt drugs and biologics from the inter partes review (IPR) process would cost the U.S. government $1.3 billion over 10 years, according to congressional staff. IPR is an administrative process for challenging the validity of patents.
CBO's cost estimate, or score, is based on assumptions that exempting drugs and biologics from IPR would delay the entry of generic competition, which would increase costs for Medicare and other government programs.
DiLenge said BIO spoke with CBO "at length" and "made a very powerful case that IPR is not designed to speed generic entry." He noted that even successful IPRs are unlikely to completely invalidate all of the patents on a drug, and said a generic competitor would be required to comply with processes and timing mandated in the Hatch-Waxman Act for any patents not invalidated by IPRs. Therefore, BIO told CBO it "didn't believe [the IPR carve-out] should score," he said.
He added that although CBO "could envision scenarios under which IPR might lead to earlier entry" of a generic competitor than without an IPR, the relatively low score -- an average of $130 million in annual savings -- indicates the non-partisan budget agency doesn't think IPRs will have a large effect on generic competition.
Although IPRs are not likely to speed generic competition, DiLenge said the biopharmaceutical industry is unified in its opposition to allowing drug patents to be challenged using the procedure, which was created in the 2011 America Invents Act (see BioCentury, May 18).
Persuading the Senate and House of Representatives to add an IPR exemption for drugs and biologics that are subject to Hatch-Waxman is a top legislative priority for BIO and PhRMA and many of their member companies. DiLenge said that IPR procedures are fundamentally unfair to patent holders because standards for invalidation are lower than those used by the courts, that defending against IPRs requires substantial financial and personnel resources, and that IPRs erode the confidence of investors in the strength of drug patents.
Amgen Inc. (NASDAQ:AMGN) and Novartis AG (NYSE:NVS; SIX:NOVN) will collaborate to co-develop and co-commercialize candidates in Alzheimer's disease and migraine.
The companies said they will combine beta-site APP-cleaving enzyme (BACE) inhibitor programs to treat AD. Novartis' CNP520, which is in Phase I/IIa testing, will be the lead candidate. Amgen will make undisclosed upfront and milestone payments to Novartis, and pay "disproportional" R&D costs for an undisclosed time frame, after which the companies will share equally global profits and costs for all AD assets.
Novartis will receive global co-development and full ex-U.S., Canada, and Japan commercialization rights to Amgen's migraine candidates including mAbs AMG 334 and AMG 301 in return for paying "disproportional" R&D costs and double-digit royalties. Novartis will have the option to commercialize one additional migraine candidate.
Both companies declined to disclose additional financial details.
Novartis spokesperson Elizabeth Power said Novartis expects to begin a study by early 2016 of CNP520 in collaboration with the Banner Alzheimer's Institute (BAI). The trial will test CNP520 in cognitively healthy volunteers at high risk of developing AD.
Power told BioCentury two Phase III trials are expected to begin this quarter of AMG 334, a human mAb inhibiting the receptor for calcitonin gene-related peptide (CGRP). AMG 301 is in a Phase I study to treat migraine.
The partners expect the deal to close this half.
AstraZeneca plc (LSE:AZN; NYSE:AZN) granted Valeant Pharmaceuticals International Inc. (TSX:VRX; NYSE:VRX) an exclusive, worldwide license to develop and commercialize brodalumab (KHK4827), excluding certain Asian territories.
AZ will receive $100 million up front and is eligible for $345 million in milestones. Valeant will cover development and regulatory costs, and the partners would share profits if brodalumab is approved.
Valeant plans to submit brodalumab for approval in the U.S. and EU in 4Q15 to treat moderate to severe psoriasis. Kyowa Hakko Kirin Co. Ltd. (Tokyo:4151) will continue to hold rights in Japan and other Asian markets under an existing agreement with Amgen.
In May, Amgen Inc. (NASDAQ:AMGN) exited its brodalumab partnership with AZ due to concerns that the compound will require restrictive labeling based on suicidal ideation and behavior seen in clinical trials (see BioCentury Extra, May 22).
Valeant declined to comment on its development plans for the human IgG2 mAb against IL-17 receptor (IL17R; IL17RA). According to ClinicalTrials.gov, Amgen terminated a Phase III trial of brodalumab to treat psoriatic arthritis and withdrew a planned Phase II trial to treat axial spondyloarthritis (see BioCentury Extra, May 26).
Valeant also declined to comment on its marketing strategy for brodalumab or its potential label. The partners expect the deal to close in 4Q15.
Alexion Pharmaceuticals Inc. (NASDAQ:ALXN) said the European Commission approved MAAs for Kanuma sebelipase alfa to treat lysosomal acid lipase deficiency (LAL-D) and Strensiq asfotase alfa to treat bone manifestations of pediatric-onset hypophosphatasia (HPP). The company plans to launch both products in October, initially only in Germany.
Kanuma is under FDA review with a Sept. 8 PDUFA date. Alexion gained the recombinant human lysosomal acid lipase (LAL) enzyme replacement therapy through its acquisition of Synageva BioPharma Corp. in June.
Strensiq, a fusion protein incorporating the catalytic domain of human tissue non-specific alkaline phosphatase (TNSALP; ALPL) and a bone-targeting peptide, is also under FDA review; its PDUFA date is undisclosed.
Separately, the EC also approved HDM-SLIT tablet from ALK-Abello A/S (CSE:ALK-B), a sublingual house dust mite (HDM) allergy immunotherapy to treat adults with HDM allergic rhinitis and HDM allergic asthma. ALK-Abello plans to launch the product within the next six months.
Bristol-Myers Squibb Co. (NYSE:BMY) and AbbVie Inc. (NYSE:ABBV) said FDA accepted and granted Priority Review to a BLA for elotuzumab (BMS-901608) in combination with other therapies as a second-line treatment for multiple myeloma (MM). BMS spokesperson Audrey Abernathy said the PDUFA date is Feb. 29, 2016.
BMS and AbbVie are co-developing the candidate. BMS, which is to lead elotuzumab's commercialization, intends to market the compound as Empliciti. The humanized mAb targeting SLAM family member 7 (SLAMF7; CS1) has breakthrough therapy designation from FDA and Orphan Drug designation in the U.S. and EU to treat MM.
The BLA included data from the Phase III ELOQUENT-2 trial, which tested elotuzumab in combination with Revlimid lenalidomide from Celgene Corp. (NASDAQ:CELG) plus dexamethasone, and the Phase II CA204-009 study, which evaluated elotuzumab in combination with Velcade bortezomib from Takeda Pharmaceutical Co. Ltd. (Tokyo:4502) and Johnson & Johnson (NYSE:JNJ) plus dexamethasone (see BioCentury Extra, May 14).
In July, EMA accepted and granted accelerated assessment to an MAA for the compound to treat MM.
BioMarin Pharmaceutical Inc. (NASDAQ:BMRN) introduced the kNOWyourDuchenne patient services program to provide free genetic testing and counseling to patients with Duchenne muscular dystrophy.
BioMarin said the program will connect patients with independent laboratories for genetic testing to profile DMD mutations. It also will provide genetic counselors to help patients determine their eligibility for clinical trials based on mutation status. VP of Commercial Operations Chuck Bucklar told BioCentury that BioMarin would cover patient costs including co-pays.
Bucklar said he expects about 30% of DMD patients to be eligible for a clinical trial based on mutation status.
BioMarin's drisapersen (PRO051), an antisense oligoribonucleotide that induces exon 51 skipping on the dystrophin gene, is under FDA and EMA review to treat DMD amenable to exon 51 skipping. The PDUFA date is Dec. 27.
Kyle Bass' Coalition for Affordable Drugs VIII filed two new inter partes review (IPR) petitions with the Patent Trials and Appeals Board (PTAB) of the U.S. Patent and Trademark Office challenging two patents from the University of Pennsylvania that cover Juxtapid lomitapide from Aegerion Pharmaceuticals Inc. (NASDAQ:AEGR).
The petitions challenge U.S. Patents Nos. 8,618,135 and 7,932,268, which Aegerion has licensed. Both patents cover dosing methods to treat hyperlipidemia and hypercholesterolemia. The '135 patent expires in 2025 and the '268 patent in 2027.
There are five Orange Book-listed patents for the small molecule microsomal triglyceride transfer protein (MTTP; MTP) inhibitor; the '268 patent is the last to expire. Aegerion markets Juxtapid to treat homozygous familial hypercholesterolemia (HoFH).
Aegerion lost $0.48 to $17.21 on Tuesday.
Trevena Inc. (NASDAQ:TRVN) gained $3.09 (52%) to $9.09 on Tuesday following news post-market Monday that TRV130 met the primary endpoint in a Phase IIb trial to treat moderate to severe acute postoperative pain after abdominoplasty surgery. Trevena plans to begin Phase III testing of the G protein-biased mu opioid receptor (MOR; OPRM1) ligand in early 2016 (see BioCentury Extra, Aug. 31).
Amgen Inc. (NASDAQ:AMGN) and partner UCB Group (Euronext:UCB) said romosozumab (AMG 785) met the primary endpoint of the Phase III STRUCTURE trial to treat osteoporosis in postmenopausal women. The compound significantly increased hip bone mineral density from baseline at 12 months compared to Forteo teriparatide in patients previously treated with bisphosphonates.
Amgen said final results from the open-label, 436-patient trial will be presented at an upcoming meeting; Amgen spokesperson Kristen Davis declined to disclose a timeline.
In 2013, Amgen and partner UCB discontinued development of romosozumab to improve fracture healing after the humanized mAb against sclerostin missed the primary endpoint in a Phase II trial (see BioCentury Extra, Feb 11, 2013).
Eli Lilly and Co. (NYSE:LLY) markets Forteo, a human parathyroid hormone (PTH) fragment.
Amgen lost $4.32 to $147.46 on Tuesday. It announced the news after market close.
A preclinical study published Tuesday in Cancer Research suggested modifying the affinity of chimeric antigen receptor T cells to their targeted antigen may improve specificity. The researchers reported lower toxicity and equal efficacy when using CAR T cells with a low affinity for EGFR compared to with high-affinity CAR therapy to treat glioblastoma in mice.
EGFR is overexpressed in glioblastoma and the study's authors hypothesized that a CAR with low affinity for the target would not bind to low-density EGFR found in normal tissues.
The researchers said tumor growth was similar after 18 days of low-affinity CAR T cell therapy compared to high-affinity CAR therapy. Six of 14 mice died within seven days of treatment with the high affinity cells (p=0.0006 vs. untreated), compared with none in the low-affinity group. All of the mice who survived after seven days were still alive after 26 days.
Mice in the low affinity group had significantly improved survival over untreated mice (p=0.0269). When the early deaths were excluded, mice in the high affinity group also had improved survival (p=0.0065).
After 225 days, two animals from each treatment group were still alive, while there were no surviving untreated mice.
The researchers generated high- and low-affinity CARs using antibodies Erbitux cetuximab and nimotuzumab (BiomAb-EGFR), which have different affinities for EGFR. The authors said that tuning the sensitivity of T cells may allow for more selective targeting of cancer cells over normal tissues.
The study was led by Laurence Cooper, who is now CEO of Ziopharm Oncology Inc. (NASDAQ:ZIOP). Cooper was a professor of pediatrics at The University of Texas MD Anderson Cancer Center during the study.
Ziopharm and Intrexon Corp. (NYSE:XON) licensed CAR T cell technology from MD Anderson in January. The companies originally partnered in 2011 to develop cancer therapies (see BioCentury Extra, Jan. 14).
Ziopharm lost $0.14 to $8.57 on Tuesday; Intrexon shed $2.73 to $41.77.
Intellia Therapeutics Inc. (Cambridge, Mass.) closed a $70 million series B round led by new investor OrbiMed. New investors including Fidelity; Janus Capital Management; Foresite Capital; Sectoral Asset Management; EcoR1 Capital; and undisclosed mutual fund and healthcare investors also participated, as did existing investors Atlas Venture and Novartis AG (NYSE:NVS; SIX:NOVN).
In January, Intellia partnered with Novartis to use the biotech's CRISPR-Cas9 technology for ex vivo engineering of chimeric antigen receptor (CAR) T cells and to develop hematopoietic stem cell (HSC) therapies (see BioCentury Extra, Jan. 7).
Intellia CEO Nessan Bermingham told BioCentury the financing will enable the company to explore in vivo applications for its gene-editing platform, starting in the liver. Bermingham declined to disclose specific liver indications.
Intellia is the third CRISPR-focused company to raise a significant sum in the past five months. Editas Medicine (Cambridge, Mass.) pulled in $120 million in a series B round in August, and CRISPR Therapeutics AG (Basel, Switzerland) raised $64 million across two financings in April.
OrbiMed's Carl Gordon will join Intellia's board.
X4 Pharmaceuticals Inc. (Cambridge, Mass.) raised $37.5 million in an equity funding round, according to an SEC filing. The company is developing oral CXC chemokine receptor type 4 (CXCR4; NPY3R) antagonists to treat refractory solid tumors.
X4 founder Renato Skerlj was among the discoverers and developers of Mozobil plerixafor, a CXCR4 antagonist marketed to mobilize hematopoietic stem cells in patients with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). Sanofi (Euronext:SAN; NYSE:SNY) gained Mozobil through its 2011 acquisition of Genzyme Corp.
X4's team includes several current and former Genzyme executives. President and CEO Paula Ragan spent six years at Genzyme and Sanofi. Former Genzyme Chairman, President and CEO Henri Termeer is X4's founding advisor and an investor.
X4's pipeline includes X4P-001 to treat refractory clear cell renal cell carcinoma and refractory epithelial ovarian cancer, as well as XP4-002 to treat glioblastoma multiforme (GBM). The company did not respond to inquiries.
CMS unveiled plans to launch the Medicare Advantage Value-Based Insurance Design Model, which will tailor coverage for patients with certain chronic conditions. Under the model, participating plans may reduce or eliminate co-pays for some items and services, including covered Part D drugs, or offer supplemental benefits to enrollees with diabetes, congestive heart failure, chronic obstructive pulmonary disease (COPD), a history of stroke, hypertension, coronary artery disease or mood disorders.
CMS will examine the model's effects on the cost of care and health outcomes. It will launch on Jan. 1, 2017, and run for five years in seven states.
Participating plans may reduce or eliminate co-pays for items or services that are identified as "high-value" for patients with certain conditions. For example, CMS said plans could eliminate co-pays for angiotensin-converting enzyme (ACE) inhibitors for enrollees with a history of acute myocardial infarction.
Other modifications could include reducing or eliminating co-pays for treatments from providers identified as "high-value," and reducing co-pays for drugs or services for enrollees who participate in a plan-sponsored disease management program.
CMS noted that enrollees in participating plans will not receive fewer benefits or have higher co-pays than other Medicare Advantage enrollees as a result of the value-based model.
The model was developed by CMS's Innovation Center. Comments are due Sept. 15.
FDA and the Drug Information Association intend to hold a meeting Sept. 9-10 to discuss oligonucleotide therapeutics. The meeting will be the sixth in about eight years to discuss updates in the field and challenges in development and regulation of the therapies.
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