Scanning electron micrograph of a human T-cell lymphocyte (National Institute of Allergy and Infectious Diseases, NIH)
27 September 2016. Early results of a clinical trial show an individual’s own immune system cells altered to attack non-Hodgkin lymphoma can cause a partial or complete response in a large percentage of patients. But the trial testing treatments, code-named KTE-C19 by Kite Pharma Inc. also show a high percentage of adverse side effects. The company reported the findings yesterday, including follow-up tests 3 months after treatments.
The trial is enrolling adult participants with with non-Hodgkin lymphoma, a cancer of lymph tissue that forms part of the body’s immune system. There are different types of non-Hodgkin lymphoma reflecting different types of white blood cells. Most adults with the disorder have either diffuse large B-cell lymphoma, which is usually aggressive, and follicular lymphoma, a slower growing cancer.
Kite Pharma, in Santa Monica, California, develops personalized cancer therapies based on the patient’s own T-cells, white blood cells that the immune system uses to fight invading pathogens. The company, founded in 2009 by UCLA urologist and cancer specialist Arie Belldegrun, is based on a technology that alters a patient’s T-cells to attack the the cancer. Belldegrun is now Kite’s CEO and board chair.
In Kite’s technology, T-cells are genetically engineered to produce chimeric antigen receptors on the cell surface that attract an antigen — a protein generating antibodies — fighting the cancer. The engineered T-cells are then grown in the lab in large quantities and infused back into the patient, where they attract the antigen proteins and fight the cancer. Early clinical trials of this technique, known as CAR-T says National Cancer Institute, show the technique has promise against advanced blood-related cancers, such as non-Hodgkin lymphoma.
The company yesterday issued a scheduled report of results from the early- and intermediate-stage clinical trial for patients with diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal large B-cell lymphoma (PMBCL), a rare form of the disease. The study tested for complete or partial response to the treatments with standard diagnostic definitions over one year, and watched for adverse reactions for 30 days. The interim results cover 62 participants in the intermediate-stage part of the trial that includes a follow-up 3 months after treatment.
The findings show of the 62 participants, 79 percent reported a partial or complete response soon after the treatment, and more than half (52%) with a complete response. After 3 months, 39 percent continued with a complete response, while another 5 percent continued to show a partial response. Most participants — 51 of 62 — had the DLBCL form of the disease, but 11 patients with the two other types showed somewhat higher response rates, both immediately and 3 months after treatment. The findings of the 62 intermediate-stage participants are similar to 7 patients enrolled in the trial’s early stage, all of whom had DLBCL.
Kite Pharma also reported high rates of severe adverse effects from the treatments, including two deaths from hemophagocytic lymphohistiocytosis, a rare life-threatening disorder from overactive immune system cells, and cardiac arrest. About two-thirds of participants reported low white blood cell counts, increasing the risk of infections. From 26 to 40 percent also reported anemia, low blood platelet counts, encephalopathy — a neurological disorder — and neurological toxicity. Some 18 percent showed signs of severe cytokine release syndrome that occurs when enzymes are emitted from cells targeted by treatments, causing flu-like symptoms such as fevers, nausea, and muscle pain, but also neurological symptoms including hallucinations and delirium.
Adverse effects are a continuing issue with CAR-T treatments. As reported in Science & Enterprise, the U.S. Food and Drug Administration in July 2016 stopped a clinical trial of CAR-T treatments for leukemia by Juno Therapeutics that caused 3 deaths. The agency allowed the trial to continue a week later after Juno submitted a revised protocol for the study.
26 September 2016. A biotechnology company is receiving a Department of Defense grant to develop a commercial-scale manufacturing process for exosomes, tiny bubbles that deliver drugs to cells in the body. The U.S. Army’s medical research agency awarded Capricor Therapeutics Inc. in Los Angeles some $2.4 million to establish a manufacturing process for exosomes, nanoscale bubbles of natural oils called lipids.
Exosomes are vesicles, tiny — 40 to 150 nanometer — lipid-membrane containers in cells that gather up and secrete cytoplasm, the gel-like material outside the cell nucleus. While originally believed to carry out waste removal and other maintenance tasks, exosomes were shown in recent years to perform useful delivery functions carrying proteins and genetic material to other cells, and drawing increased attention from a range of biological disciplines.
Capricor is a biotechnology enterprise specializing in regenerative medicine, in particular the extraction of cells known as cardiospheres producing stem cells that are introduced back into the coronary arteries of the patient. Capricor says cardiosphere-derived stem cells release growth factors and cytokines, cells that stimulate specific cell responses, signaling the heart to repair itself.
The company is licensing technology from Cedars-Sinai Medical Center in Los Angeles that also extracts exosomes from cardiosphere-derived cells. The company’s first application of exosomes is ocular graft-versus-host disease, a disorder, an immune system disorder that occurs after stem cell or bone marrow transplants. Complications of graft-versus-host disease affecting the eyes include dry eye syndrome and acquisition of eye-related allergies from donors. People with grant-versus-host disease may need to take drugs that suppress the immune system, which raises the risk for infection.
The U.S. military is interested in exosomes as vehicles for reliable, self-contained drug delivery and diagnostics in the field. Among the applications being considered are “nanobots” transported by exosomes with small interfering RNAs, genetic content, or fluorescent reporters. An essay published by the Army earlier this year finds “intriguing” the prospect of manufacturing exosomes loaded with diagnostic or therapeutic payloads.
Capricor first exosome product for ocular graft-versus-host disease is code-named CAP–2003, for which the company expects to file an investigational new drug application in 2017. Linda Marbán, Capricor’s president and CEO says in a company statement, “As a cell-free material, CAP-2003 can be handled and stored in similar fashion to a traditional biopharmaceutical, and may be better suited than cell-based therapeutics for certain applications.”
Marbán adds that “As we advance and expand our exosomes program, this grant from the DoD will support our objective of achieving a commercial manufacturing process for a candidate which we believe has broad treatment potential.”
23 September 2016. Two new spin-off enterprises are being created to develop gut-based treatments for chronic diseases using technologies from synthetic biology company Intrexon Corporation. Dollar amounts of the licensing and investment transactions were not disclosed.
Intrexon in Germantown, Maryland is creating Genten Therapeutics Inc. to design therapies for celiac disease, while CRS Bio will develop therapies for chronic rhinosinusitis. Celiac disease is an inherited autoimmune disorder, where the body’s immune system reacts to gluten, a protein found in wheat, rye and barley. The immune reaction destroys the nutrient absorption capacity of the small intestine, leading to tissue damage. About 1 percent of people worldwide have celiac disease, with the only protection against symptoms being a strict gluten-free diet.
Rhinosinusitis is an infection or irritation of the lining of sinuses in the face and head, creating extra mucus and nasal congestion, discharge into the throat, a decreased sense of smell, and facial pain or pressure. In most cases, rhinosinusitis is temporary, known as acute rhinosinusitis, but when the condition become more persistent, lasting for 12 weeks or longer, it is called chronic rhinosinusitis. The chronic condition is more complex, with causes more elusive. and characterized in some cases with growth of polyps in the nasal passages. The disease is associated with allergies, immune system disorders, exposure to cigarette smoke or airborne irritants, and other causes.
Both Genten Therapeutics and CRS Bio are licensing Intrexon’s ActoBiotics technology to develop their treatments. Intrexon’s technologies are derived from computational models and software that assemble DNA-based solutions on a commercial scale. The ActoBiotics platform creates engineered food-grade bacteria, known as Lactococcus lactis, similar to those found in yogurt, to deliver protein therapeutics into the gut, which would otherwise degrade in the gastrointestinal tract.
Genten is expected to apply ActoBiotics to express gluten peptides, either alone or with enzymes that control immune responses, to help people with celiac disease reestablish a tolerance for gluten. CRS Bio plans to direct ActoBiotics technologies to generate antibodies that block inflammatory signals in the nasal passages of people with chronic rhinosinusitis, both with and without nasal polyps, to reduce inflammation and improve their breathing.
Intrexon calls these types of agreements exclusive channel collaborations that give the partner companies an exclusive license to develop new products from Intrexon technologies, move those products through regulatory processes, and conduct marketing and sales. For Genten Therapeutics and CRS Bio, Intrexon is receiving a 25 percent equity stake, along with milestone payments and royalties later on.
Intrexon’s investments in the two companies are funded by Harvest Capital Strategies, the asset management division of JMP Group in San Francisco. In January 2016, JMP Group established the Harvest Intrexon Enterprise Fund to finance new enterprises developing Intrexon’s synthetic biology technologies.
23 September 2016. Monsanto Company is licensing genomic editing technology for agricultural applications from a joint research center at Harvard University and MIT. Financial aspects of the agreement between the Broad Institute at Harvard and MIT and Monsanto were not disclosed.
Monsanto, in St. Louis, is a designer of seeds and soil treatments often using genetic engineering to create new varieties to meet conditions faced by growers. The Broad Institute is a research center investigating advanced scientific issues in the life sciences primarily for biomedical applications.
The institute’s labs are among the pioneers in developing clustered, regularly interspaced palindromic repeats or Crispr, a technology based on bacterial defense mechanisms that uses RNA to identify and monitor precise locations in DNA. The actual editing of genomes with Crispr uses an enzyme known as Crispr-associated proteins or Cas. With this approach to Crispr, RNA molecules guide Cas proteins to specific genes needing repair, making it possible to address root causes of many diseases.
The deal with Monsanto gives the company a worldwide non-exclusive license to Broad Institute’s patents for Crispr-Cas technologies. As reported in Science & Technology in December 2015, Feng Zhang and colleagues at Broad Institute designed enhancements to Crispr, making genomic edits with Cas enzymes more accurate, while maintaining Crispr’s simplicity and efficiency.
Those patents, however, are being challenged by University of California at Berkeley that claims it filed a patent for Crispr before the Broad Institute, while Broad Institute says its technology is more applicable to mammalian cells. The U.S. Patent and Trademark Office, and its counterpart in Europe, are expected to rule on these challenges soon.
The financial implications of the rulings are enormous. Zhang is is one of the founders of Editas Medicine, a company applying Crispr to inherited diseases, which in February 2016 raised $94 million in its IPO. In May 2016, Intellia Therapeutics which licenses Crispr technology from UC-Berkeley, raised $108 million in that company’s IPO.
Monsanto says it plans to apply the search-and-replace functions of Crispr-Cas to designing new seed varieties. The company anticipates applying the the technology to add beneficial characteristics to crops or remove undesirable traits more efficiently.
Monsanto is not the first organization to apply Crispr to crops. In February 2016, University of California in Riverside received funding from U.S. Department of Agriculture to adapt Crispr-Cas genome editing for producing varieties of fruit resistant to citrus greening, a bacterial disease devastating citrus crops in the U.S. and elsewhere.
22 September 2016. An analysis of data from health surveys shows malnutrition associated with 8 common chronic diseases adds $15.5 billion directly to U.S. health care costs. A calculation of these costs, with estimates for each state are published in yesterday’s (21 September) issue of the journal PLoS One.
A team from health care products company Abbott in Abbott Park, Illinois sought to put a reliable price tag on the economic burden of malnutrition, a condition considered treatable and preventable, among people with chronic diseases, as well as note geographic variations of this burden within the U.S. Among the items offered by Abbott are nutritional products for people with chronic diseases, such as diabetes, cancer, and kidney disease.
Earlier studies produced broad estimates of costs related to malnutrition, including additional medical expenses linked directly to malnutrition, as well as indirect costs, extra expenses incurred as a result of the burden placed on others, such as care givers and family members. The authors led by Abbott health economist Scott Goates focused their investigation on direct costs, to provide a more actionable calculation for policy makers, and a common target for state-by-state estimates, as well as breakdowns by age, race, and sex.
Goates and colleagues drew their data from two large-scale national health care surveys, National Health and Nutrition Examination Survey, or Nhanes, and National Health Interview Survey over 6 years. The researchers looked specifically at variables related to nutrition among people with 8 chronic diseases: stroke, chronic obstructive pulmonary disease or COPD, coronary heart failure, breast cancer, dementia, musculoskeletal disorders, depression, and colorectal cancer.
The Abbott team calculates that malnutrition adds $15.5 billion a year in direct expenses each year in health care costs. The highest added health care costs from malnutrition are found among people with dementia, accounting for more than half ($8.7 billion) of the total. Breast cancer generates the fewest additional direct costs due to malnutrition, $76 million.
Older individuals, those 65 and over — the age group most likely to suffer from dementia — accounted for $4.3 billion of the added direct costs, nearly one-third of the total. Among this group, people with chronic disorders can experience trouble chewing or swallowing. The researchers indicate many patients with these conditions arrive at the hospital with malnutrition, even if obese, or become malnourished at the hospital, which can increase the risk of complications or delay recovery.
As one would expect, states with larger populations like California ($1.7 billion) have the highest additional costs from malnutrition, while smaller states such as Wyoming ($25 million) have the lowest additional costs. On a per capita basis, the District of Columbia pays $65 more per patient as a result of malnutrition, compared to $36 per patient in Utah.
The authors recommend more attention in hospitals to nutritional issues and point to successful pilot programs where better screening and treatment processes contribute to reduced length of stays, fewer readmissions, and lower costs of care for patients. Carol Braunschweig, professor kinesiology and nutrition at University of Illinois in Chicago, and one of the paper’s co-authors, notes in an Abbott statement, “A great deal of research has demonstrated malnutrition negatively impacts health and increases costs to our health care system. By emphasizing the importance of nutrition, from identifying and treating people in the hospital to following up with them once they leave, we can improve people’s health and save money in the process.”
22 September 2016. Findings from a clinical trial show a candidate drug kills bacteria causing a type of gonorrhea becoming resistant to current antibiotics. Results of the trial testing the drug code-named ETX0914 made by biotechnology company Entasis Therapeutics are scheduled for presentation tomorrow at the 2016 STD Prevention Conference in Atlanta.
Gonorrhea is a sexually transmitted disease causing infections in the genitals and other regions, which has become common among people ages 15 to 24. Infections from Neisseria gonorrhoeae bacteria are a major cause of pelvic inflammatory disease in the U.S., which can lead to conditions in women such as tubal infertility, ectopic pregnancy, and chronic pelvic pain, as well as promote HIV infection. Centers for Disease Control and Prevention says gonorrhea is the second most reported sexually transmitted disease, with more than 350,000 new cases found in the U.S. during 2014.
The current primary treatment for gonorrhea is a type of antibiotics known as cephalosporins. In recent years, however, the bacteria causing gonorrhea evolved to become more resistant to cephalosporins, creating a need for new drugs to combat the disease. One of those new drugs is ETX0914, developed as an alternative to cephalosporins.
Entasis Therapeutics is a spin-off company from drug maker AstraZeneca, founded last year in Waltham, Massachusetts and given the rights to AstraZeneca’s small molecule, or low molecular weight, anti-infection drug candidates, including ETX0914. Entasis uses what it calls non–culture-based diagnostic testing to identify specific targets among drug-resistant bacteria for new antibiotics. ETX0914 is the only one of 4 Entasis antibiotics in development to reach beyond early-stage trials.
This intermediate-stage clinical trial tested ETX0914 among 179 individuals age 18 to 55 with urethral or cervical gonorrhea. The study was conducted by National Institute of Allergy and Infectious Diseases, part of National Institutes of Health, and led by Stephanie Taylor, professor of microbiology at Louisiana State University medical school in New Orleans. Taylor is scheduled to report the findings at tomorrow’s meeting.
Participants in the trial — 167 men and 12 women — were randomly assigned to receive oral ETX0914 doses of 2 or 3 grams, or injections of a cephalosporin antibiotic. The study team looked primarily for the clearance of infections in the affected regions after 6 days, and reports of adverse effects within 31 days after treatment.
The results show all 47 participants receiving 3 grams of ETX0914, and nearly all — 48 of 49 individuals — receiving 2 grams, were cured of their gonorrhea infections. Some 21 of the 179 participants reported adverse side effects, characterized as mild and primarily gastrointestinal.
Entasis expects to begin a late-stage clinical trial of ETX0914 in 2017. The company says FDA is giving the drug fast-track designation that offers accelerated review of treatments with a potential to address serious conditions or unmet medical needs. With fast-track status, FDA schedules more frequent meetings, and allows for more frequent correspondence, partial submissions, and rolling review of a company’s new-drug or biological license applications.
RNA molecule illustration (Nicolle Rager Fuller, National Science Foundation)
21 September 2016. Biotechnology company BioNTech AG is licensing its messenger RNA technology and collaborating with biopharmaceutical company Genentech to develop personalized cancer immunotherapies. The deal is expected to bring BioNTech, in Mainz, Germany at least $310 million in the early stages of the partnership. Genentech is a division of the Roche Group in South San Francisco, California.
BioNTech is an 8-year old company spun off from Johannes-Gutenberg University in Mainz developing immunotherapies from synthetic forms of messenger RNA, a nucleic acid related to DNA used by cells to produce the amino acids in proteins for carrying out functions in the body. An objective of the partnership is to adapt BioNTech’s messenger RNA technology to Genentech’s work in cancer immunotherapies to design treatments reflecting a cancer patient’s individual tumor composition. Another goal, say the companies, is to apply this therapeutic approach to a wide range of cancers.
Genentech researchers led by cancer immunologist Lélia Delamarre published a study in 2014 showing in lab animals the feasibility of cancer immunotherapies attacking precise targets identified through genomic sequencing. Delamarre notes in a Genentech essay that identifying targets for cancer vaccines is more difficult than vaccines for infectious diseases. “Vaccines work by exposing the immune system to ‘non-self’ proteins known as antigens,” says Delamarre, “priming it to recognize and eliminate the invaders. But in the case of cancer cells, most proteins are the same as those on healthy cells. This makes it hard to identify which antigen to use in a vaccine.”
One of BioNTech’s initiatives aims to address this issue through its Individualized Vaccines Against Cancer or Ivacs, that target unique mutations in a patient’s cancer genes identified through high-throughput genomic sequencing. Algorithms go through the sequencing results to compare healthy to cancerous cells, identifying the mutanome, the unique set of cancer-related mutations for each patient. Ivac vaccines encode the precise targets, called neoantigens, in synthetic messenger RNA, highlighting the epitopes, or precise binding locations for T-cells in the immune system to attack cancer cells. The vaccine then stimulates T-cells to attack only the cancer cells programmed in the messenger RNA, and ignoring healthy cells and tissue.
BioNTech is testing Ivac-mutanome vaccines in early-stage clinical trials with patients having breast cancer and melanoma, or advanced skin cancer. The collaboration is expected to broaden that portfolio to a wider variety of cancer types.
The agreement calls for Genetech and BioNTech to share all development costs and profits from designated therapy programs. BioNTech will manufacture vaccines for clinical trials, while Genentech will be responsible for manufacturing vaccines once commercialized, with BioNTech maintaining an option to manufacture vaccines for the worldwide supply chain.
Genentech will pay BioNTech $310 million in initial licensing fees and meeting early developmental milestones. In addition, BioNTech will have rights to co-promote certain products in the United States and major European countries, including Germany.
In the following video, Genentech tells more about this individualized approach to cancer immunotherapies.
21 September 2016. Biomedical Advanced Research and Development Authority, or BARDA, signed agreements worth $67 million to develop new treatments and diagnostics for urgent drug-resistant infections. The collaborations between BARDA, in the U.S. Department of Health and Human Services, and The Medicines Company in Parsippany, New Jersey and Roche Group in Basel, Switzerland could be extended to include other treatments for drug-resistant bacteria, valued at more than $283 million.
BARDA promotes development of countermeasures against public health emergencies, including bacteria resistant to current antibiotics and other infectious disease epidemics. Antibiotic resistance continues to be difficult problem for clinicians and public health authorities, reaching a crisis stage in some parts of the world. Centers for Disease Control and Prevention says 2 million people in the U.S. each year contract infections from bacteria resistant to antibiotics, leading to at least 23,000 deaths.
The $32 million agreement with The Medicines Company supports a late-stage clinical trial of the drug Carbavance to treat gram-negative infections in hospital-acquired and ventilator-associated bacterial pneumonia. Gram-negative bacteria are associated with conditions such as pneumonia, bloodstream infections, wound, and surgical site infections. “Gram” refers to a classification for bacteria where the microbes either retain (gram-positive) or shed (gram-negative) a test stain on their protective cell coatings.
Carbavance is a combination of the antibiotics carbapenem and meropenem, with vaborbactam, a beta-lactamase inhibitor protein. Beta-lactamase inhibitors act as a catalyst, increasing the potency of other antibiotics used in combination. In an earlier BARDA contract, The Medicines Company evaluated Carbavance as a treatment for complicated urinary tract infections and infections caused by Enterobacteriaceae bacteria resistant to carbapenem, rated by CDC as one of the most urgent drug-resistant bacterial threats.
The $35 million agreement with Roche covers development of new diagnostic tests for specific bacterial and viral infections. Roche is active in the field of infectious diseases both as a provider of diagnostics as well as pharmaceuticals.
BARDA is using authority granted under the Pandemic and All Hazards Preparedness Act of 2006 to establish provisional cost-sharing agreements with both companies for portfolios of drugs to combat antibiotic-resistant bacteria. Under this authority, BARDA has options valued at $132 million with The Medicines Company for further development of new antibiotic-resistant bacterial drugs over 5 years.
The agency has a similar arrangement with Roche, valued at $151.6 million over 5 years. This agreement supports development of a drug candidate that works with other drugs to combat infections from drug-resistant bacteria. The deal also has options for discovery of new drugs to treat antibiotic-resistant bacterial infections.
BARDA says each company will provide a significant portion of the funding to bring the products to market, although the amounts of company funds were not disclosed. “These partnerships allow BARDA and its partners to respond rapidly to new discoveries, technical developments, and strategic priorities by quickly refocusing our portfolios,” says BARDA’s acting director Richard Hatchett in an agency statement.
20 September 2016. A clinical trial is recruiting participants to test a product with live skin bacteria as a treatment for adult acne. The intermediate- and late-stage trial, testing a therapy made by biotechnology company AOBiome LLC in Cambridge, Massachusetts, is also using mobile devices with participants for remote data collection.
AOBiome develops skin care cosmetics and treatments seeking to reintroduce bacteria that oxidize ammonia eliminated from the skin microbiome through modern hygienic practices. Ammonia-oxidizing bacteria, says the company, convert ammonia and urea from perspiration to nitrite and nitric oxide. Nitrite helps control the growth of other microbes, including pathogens, while nitric oxide is a signaling molecule that helps regulate inflammation.
Acne, known medically as acne vulgaris, is a chronic inflammatory condition that blocks hair follicles and sweat glands, primarily on the face, chest and back, affecting some 80 million people in the U.S., according to data cited by the company. AOBiome says eliminating commensal or natural bacteria from the skin also removes the nitric oxide leaving the skin as a pro-inflammatory environment. The product tested in the clinical trial, code-named B244, is a topical spray that applies ammonia-oxidizing bacteria to the skin thus restoring the natural microbial balance controlling skin inflammations such as acne.
The intermediate- and late-stage clinical trial plans to recruit 372 individuals age 18 and older with mild to moderate cases of acne. Participants will be randomly assigned to spray either B244 or a placebo to the face twice a day for 12 weeks. The primary outcome measures for the study are counts of inflammatory acne lesions on the skin as well as improvement on a quality of life index scale. The trial is also evaluating the safety and tolerability of treatments, and measuring skin microbes on the face every 4 weeks.
The trial has another notable feature, the use of telemedicine for data collection. AOBiome is partnering with Science 37, a contract research organization in Culver City, California that offers remote data-gathering service known as Network Oriented Research Assistant, or Nora. The service connects clinical trial participants at their homes to Science 37, in this case to collect counts of acne lesions and other measures, with smartphones provided for the study. Previously, trial participants, or dermatology patients in general, would need to travel to doctors’ offices to evaluate progress.
AOBiome is testing B244 in clinical trials with other inflammatory conditions such as dermatitis, rosacea, and allergic rhinitis or hay fever. AOBiome is a 3-year old enterprise, whose founders include David Whitlock, an MIT-trained chemical engineer, who told the Boston Globe last year he hasn’t showed since the year 2000. Whitlock instead prefers to maintain microbial balance on his skin with the company’s consumer skin care products, marketed under the brand name Mother Dirt.
20 September 2016. Teva Pharmaceutical Industries is licensing from biotechnology company Regeneron Pharmaceuticals an engineered antibody that targets proteins supporting pain signals. The agreement could bring Regeneron, in Tarrytown, New York as much as $1.25 billion in licensing fees and R&D reimbursements, more in milestone and royalty payments.
The deal involves fasinumab, a synthetic antibody that addresses a specific protein, nerve growth factor, or NGF supporting development and survival of nerve cells transmitting pain, temperature, and touch sensations. New drugs are needed to replace opioid pain relievers responsible for a growing epidemic of abuse and overdoses. The companies cite data from market research company Decisions Resources Group that 30 million people in the U.S. live with osteoarthritis pain, and a similar number with chronic low back pain, many at moderate to severe levels.
Fasinumab binds to NGF and blocks its signals, reducing pain sensitization. Regeneron says its preclinical tests show other nerve cell signals are not affected by the drug. Other preclinical tests, however, show fasinumab and similar experimental drugs addressing NGF have toxic effects on the sympathetic nervous system that activates fight-or-flight responses in some lab animals. Those results led FDA in December 2012 to suspend testing of anti-NGF drugs with humans until the toxicity questions were resolved.
FDA later lifted its suspension, allowing Regeneron in mid-2015 to begin an intermediate- and late-state clinical trial of fasinumab with individuals experiencing moderate or severe knee or hip pain from osteoarthritis. The company reported its first results of the trial in May 2016, showing participants receiving 4 doses of fasinumab over 12 weeks, with pain measured on a 10-point standard rating scale at 16 weeks. The results show participants receiving fasinumab at 4 different dosage levels experienced less pain compared to baseline measures than individuals receiving a placebo. Occurrences of adverse events — joint pain, tingling sensations, numbness, and swelling — were similar for treatment and placebo groups.
The deal calls for Regeneron to lead further development of fasinumab and commercialization in the U.S., while both companies will share sales and marketing responsibilities in the U.S. Teva, based in Israel, will lead commercialization of fasinumab outside the U.S., except for Japan, Korea and 9 other Asian countries where Regeneron and Mitsubishi Tanabe Pharma Corp. already have a licensing agreement. China is not one of 9 countries.
The agreement gives Regeneron an initial licensing fee of $250 million from Teva, as well as payments of about $1 billion covering continuing research and development of fasinumab. Regeneron is also eligible for development and regulatory milestone payments, and royalties based on net sales.
Regeneron is recruiting participants for intermediate- and late-stage clinical trial of fasinumab among individuals with chronic lower back pain, as well as a long-term safety and efficacy study of the drug with people having knee or hip pain from osteoarthritis.
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