The FDA has granted Orphan Drug Designation (ODD) to Adaptimmune Therapeutics’ (NASDAQ:ADAP) SPEAR T-cells targeting MAGE-A4 (ADP-A2M4 program) for the treatment of soft tissue sarcomas.
Adaptimmune is currently investigating its ADP-A2M4 SPEAR T-cells in two types of sarcoma: synovial sarcoma and MRCLS.
Among the benefits of Orphan Drug status in the U.S. is a seven-year period of market exclusivity for the indication, if approved.
Alexion Pharmaceuticals (NASDAQ:ALXN) and BridgeBio Pharma’s (NASDAQ:BBIO) subsidiary Eidos Therapeutics (NASDAQ:EIDX) have announced an agreement that grants Alexion an exclusive license to develop and commercialize AG10 in Japan.
AG10 is a small molecule designed to treat the root cause of transthyretin amyloidosis (ATTR) – destabilized and misfolded transthyretin (TTR) protein – by binding and stabilizing TTR in the blood.
Eidos is currently evaluating AG10 in a Phase 3 study in the U.S. and Europe for ATTR cardiomyopathy and plans to begin a Phase 3 study in ATTR polyneuropathy in H2 2019.
Under the terms of the agreement, Eidos will receive an upfront payment of $25M and an equity investment of $25M, with the potential for additional Japanese-based milestone- and royalty-dependent payments.
ACADIA Pharmaceuticals (NASDAQ:ACAD) is up 68% premarket on increased volume in reaction to successful results in a Phase 3 clinical trial, HARMONY, evaluating lead drug NUPLAZID (pimavanserin) for the treatment of dementia-related psychosis.
The study met the primary endpoint of a statistically significant longer time to relapse of psychosis compared to placebo based on a planned interim analysis so the study will be stopped early.
The data will be submitted for presentation at future medical conferences. The company expects to file a supplemental marketing application in the U.S. in 2020.
The FDA approved NUPLAZID in April 2016 for Parkinson’s disease psychosis.
A Phase 3 study in schizophrenia patients was unsuccessful.
Management will host a conference call this morning at 8:30 am ET to discuss the results.
Amgen (NASDAQ:AMGN) is down 4% premarket on light volume after announcing updated data from a Phase 1 clinical trial evaluating AMG 510 in patients with previously treated KRAS G12C-mutated solid tumors. The results were presented at the World Conference on Lung Cancer in Barcelona.
Investors appear disappointed with the partial response rate of 54% (n=7/13) in the highest dose (960 mg/day) cohort compared to 50% (n=5/10) reported at ASCO in June. The updated disease control rate (responders + stable cancer) was 100% (n=13/13) versus 90% (n=9/10) before.
On the safety front, there were no dose-limiting toxicities and no adverse events (AEs) leading to discontinuation. The rate of mild/moderate AEs was 26% (n=9/34) while the rate of serious AEs was 9% (n=3/34).
AMG 510 is a KRAS G12C inhibitor.
Fellow KRAS G12 inhibitor developer Mirati Therapeutics (NASDAQ:MRTX) is down 4% premarket as well.
GoodRx, a healthcare savings company, will partner with AAA to offer its 59 million members exclusive savings on prescription drugs.
AAA members will have access to coupons and discounts that will help them save up to 85 percent on prescriptions.
The partnership gives AAA members 5 percent to 10 percent more off the price of prescriptions than current coupons and discounts available to other customers.
The coupons are usable at over 70,000 pharmacies across the U.S., including CVS and Walgreens.
The holiday-shortened week saw a few huge moves by individual stocks.
Abeona Therapeutics Inc ABEO 1% was among the biggest gainers after the biopharma announced plans to explore strategic alternatives. On the other hand, Mallinckrodt PLC MNK 18.24% came under intense selling following reports of a potential bankruptcy filing.
Here are they key events for the upcoming week.
Conferences
International Association for the Study of Lung Cancer (IASLC) 2019 World Conference – Sept. 7-10, in Barcelona, Spain
32nd European College of Neuropsychopharmacology (ECNP) Congress – Sept. 7-10, in Copenhagen, Denmark
19th Congress of the International Headache Society – Sept. 5-8, in Dublin, Ireland
World Congress on Pain Medicine and Management – Sept. 9-10, in Singapore City, Singapore
31st International Conference on Cancer Research and Therapy – Sept. 9-10, in Zurich, Switzerland
H.C. Wainwright Annual Healthcare Conference 2019 – Sept. 9-10, in Lotte New York Palace Hotel, New York
Morgan Stanley 17th Annual Healthcare Conference – Sept. 9-11, in Grand Hyatt, New York City, New York
35th Congress of the European Committee For Treatment and Research In Multiple Sclerosis (ECTRIMS) – Sept. 11-13, in Stockholm, Sweden
Society for Research in Nicotine and Tobacco Europe 10th Annual Conference – Sept. 12-14, in Oslo, Norway
17th International Myeloma Workshop – Sept. 12-15, in Boston, Massachusetts
12th World Congress on Cell & Tissue Science – Sept. 13-14, in Singapore City, Singapore
Heart Failure Society of America 23rd Annual Scientific Meeting – Sept. 13-15, in Philadelphia
PDUFA Dates
Xeris Pharmaceuticals Inc XERS 0.56% awaits FDA verdict on its NDA for Gvoke – a ready-to-use glucagon injection – for treating severe hypoglycaemia. The PDUFA action date is scheduled for Tuesday.
The FDA is set to rule on Ardelyx Inc ARDX 2.79%‘s NDA for tenapanor in treating irritable bowel syndrome with constipation. The decision date is set for Thursday.
FDA’s Allergenic Products Advisory Committee is scheduled to meet Tuesday to discuss and make recommendations on the safety and efficacy of Aimmune Therapeutics Inc AIMT 2.37%‘s Allergen Powder indicated for the treatment to reduce the risk of anaphylaxis after accidental exposure to peanut in patients aged 4 to 17 years with a confirmed diagnosis of peanut allergy.
Clinical Trial Readouts
Adverum Biotechnologies Inc ADVM 0.66% is due on Thursday to release 24-week data from the first cohort of a Phase 1 study evaluating its ADVM-022 in wet age-related macular degeneration.
IASLC World Conference Presentations
Beyondspring Inc BYSI 19.15% – presentation of already-released Phase 3 data for plinabulin in chemotherapy-induced neutropenia (Sept. 8)
Seattle Genetics, Inc. SGEN 1.25% & GENMAB A/S/S ADR GMAB 0.9% – initial Phase 1/2 data for enapotamab vedotin in solid tumors (Sept. 8)
Eli Lilly And Co LLY 0.46% – updated Phase 1/2 data for LOXO-292 in RET-fusion non-small cell lung cancer (Sept. 8)
Amgen, Inc. AMGN 0.04% – Updated Phase 1 data for AMG 510 in solid tumors (Sept. 8)
AstraZeneca plc AZN 0.04% – already-released interim Phase 3 data for imfinzi and tremelimumab in small cell lung cancer (Sept. 9)
IHC Congress Presentations
Zosano Pharma Corp ZSAN 3.4% – long-term safety data from a Phase 3 study of Qtrypta in migraine (Sept. 8)
ECNP Congress Presentations
Concert Pharmaceuticals Inc CNCE 2.01% – Phase 1 data for CTP-692 in schizophrenia (Sept. 10)
ECTRIMS Congress Presentations
Atara Biotherapeutics Inc ATRA 0.43% – initial Phase 1 data for ATA188 in multiple sclerosis (Sept. 11)
Roche Holdings AG Basel ADRRHHBY 0.9% – Phase 3 data for satralizumab in neuromyelitis optica spectrum disorder (Sept. 11)
TG Therapeutics Inc TGTX 3.66% – Phase 2 long term follow up data for TG-1101 in relapsing form of multiple sclerosis.
Novartis AG NVS 0.19% and Genmab – already released Phase 3 data for OMB158 in relapsing multiple sclerosis.
Other Conference Presentations
Achieve Life Sciences Inc ACHV 2.7% – already-released Phase 2b data for Cytisine in smoking cessation at the SRNT conference (Sept. 13)
Cytokinetics, Inc. CYTK 1.12% – Phase 1 data from healthy volunteers for CK-3773274 in hypertrophic cardiomyopathy
Cellectar Biosciences Inc CLRB 1.86% – Poster presentation of Phase 1 data for CLR 131 in multiple myeloma at the International Myeloma Workshop (Sept. 14)
IPOs
10x Genomics, a provider of single-cell sequencing platform for biomedical research, is planning to offer 9 million shares in an IPO at an estimated price range of $31-$35. The company is seeking to list its shares on the Nasdaq under the ticker symbol TXG.
Satsuma Pharmaceuticals, which is developing, a fast-acting dry powder nasal spray for migraines, is planning a 5-million share IPO to be priced between $14 and $16. The shares are to be listed on the Nasdaq under the ticker symbol STSA.
SpringWorks Therapeutics, a developer of small-molecule therapies for rare cancers, is planning to offer 7.353 million shares in an IPO. The company expects to price the offering in the $16-$18 range, with the shares to be listed on the Nasdaq under the ticker symbol SWTX.
Can concurrent cannabinoid and opioid use enhance analgesic effects, or should their combined use be avoided? Presenters at the 2019 PAINWeek conference took on this question, agreeing that many of the effects associated with cannabinoids remain unknown.
“I feel like I’m speaking to the choir here — this is something we’re all dealing with already,” said Chris Herndon, PharmD, of Southern Illinois University in Carbondale, Illinois, at a talk entitled “Cannabis and Opioid Together: Syn or Synergy?”
The proportion of patients in primary care clinics that are on chronic opioid therapy and using cannabis has been reported to be anywhere from 16% to 25%, Herndon said. As such, the potential harms and benefits are certainly something that “need to be discussed.”
There are as many as 400 constituents of the cannabis plant, 66 of which are of the cannabinoid structure, including tetrahydrocannabinol (THC) and cannabidiol (CBD).
They each have a number of different pharmacological modalities, many of which support the idea of using these drugs to treat pain, including calcium channel antagonism, downstream effects on lysergic glutamatergic, and potential N-methyl-D-aspartate receptor (NMDA) activity, Herndon said.
He cited one recent study that found adding medical cannabis to opioid therapy among fibromyalgia patients was associated with significant improvements in pain, measured through the visual analog scale, fibromyalgia pain severity scales, and disability measures.
However, cannabis may affect pain tolerance in a bell or j-shaped curve, in which stimulating pain receptors at certain levels can actually produce a hyperalgesic effect, countered Bradlee Rea, PharmD, of Kaweah Delta Health Care in Visalia, California.
“THC may actually reduce a patient’s tolerance or ability to tolerate pain,” Rea said.
Herndon argued that at the right ratio, CBD and THC together have been shown to reduce pain. For example, one study that tested four different cannabis varieties in patients with fibromyalgia found much greater improvements in pain with Bediol — which contains 13.4 mg THC and 17.8 mg CBD — than with Bedrocan, which contains mostly THC (22.4 mg THC and <1 mg CBD).
But the problem is that in practice, medical marijuana can be a “potpourri surprise,” Rea said, and the majority of studies examining analgesic effects of cannabidiol are not standardized in terms of strain, species, or dosing.
“We have agonists, we have antagonists, we have inverse agonists,” Rea said. “How do we figure out what is going on when we have so many different products in the flower of cannabis? How do we know what product is doing what without more data looking at least in vitro at some of these constituents found in marijuana?”
Rea added that cannabidiol could be functioning by changing how patients perceive their pain, reducing pain catastrophizing, or decreasing the amount of other medications they use.
Herndon said in a clinical environment that is increasingly encouraging opioid alternatives, this could be one advantage to cannabinoids. In a 2019 study, nearly three-quarters of patients who completed a survey said they were able to completely terminate their opioid use after they started using cannabis for chronic pain, he noted. Another survey found just over one-third of patients authorized to use medical cannabis in Canada were able to substitute cannabis for prescription opioids.
“There are those who would get up and argue with me, and say they’re just substituting one drug for another, or potentially they were using prescribed opioids for non-therapeutic intent,” Herndon said. “But I think showing the change in non-opioid analgesics like some of these studies do supports my premise.”
However, cannabis is not without its own side effects, including associations with increased anxiety, depression of the central nervous system, and decreased testosterone production. But all of those have also been linked with opioid use, Rea said.
Patients with underlying depression and anxiety may be even more vulnerable to some comorbidities associated with both drugs, Rea said. For example, in one study in Israel examining patients on concomitant medical cannabis and opioids, patients with depression and anxiety were significantly more likely to show signs of misuse for both drugs.
“Chronic pain isn’t just chronic pain — it can be coupled with stress, anxiety, sleep disturbances, and PTSD [post-traumatic stress disorder],” Rea said. “All of these do have an effect on how people perceive their pain. It’s important to look at the whole picture and treat the whole picture versus just treating the chronic pain.”
Currently, 22 states permit the use of medical marijuana, each with different regulations and products. In New York, Colorado, and Illinois, for example, clinicians can now prescribe medical cannabis as a substitute for opioids. Ultimately, there are many factors that go into the decision, which should jointly be made by the provider and patient, Herndon said.
“We’re trying to balance what’s working for the patient, and trying to provide compassionate care with what little we know about this substance, and the different constituents, and how it might impact the drugs they’re already on,” Herndon said. “Then also making sure you protect yourself as a prescriber because you’re providing care for these patients.”
Herndon and Rea disclosed no relevant relationships with industry.
