Search This Blog

Thursday, July 5, 2018

Biotech catalysts coming up in 2H 2018


Biotech stocks carved out modest gains in the first half of 2018 and outperformed the broader market, although their gains paled before those of the tech-weighted Nasdaq Composite Index. From the fundamental perspective, there was no lack of catalytic events such as FDA decisions, clinical trial results announcements and mergers and acquisitions.
Here’s a listing of some individual biotechs that moved notably in either direction in the first half of the year.

Stocks That More Than Doubled

The 5 Worst Declines

IBB Vs. S&P 500 Vs Nasdaq Composite Index

IBB Chart
Source: YCharts

NME Approvals

New molecular entities are products that contain active moieties that haven’t been previously approved by the FDA, either as a single ingredient drug or as part of a combination product. The number of NME approvals are usually considered a measure of innovation in drug research. So far in 2018, the number of NME approvals totaled 17 — a big number, though smaller than the 23 approvals made in the same period last year. Click here to learn about FDA’s NME approvals for the first half.

Launches With Blockbuster Potential

A handful of drugs with blockbuster potential were launched in the first half:
Gilead Sciences, Inc. GILD 1.89%‘s AIDS cocktail Biktarvy, a concoction of bictegravir 50mg, emtricitabine 200mg and tenofovir alafenamide 25mg. A once-daily single tablet regimen for HIV-1 infection was approved by the FDA Feb. 7. Biktarvy’s sales could touch $6.1 billion by 2024, Evaluate Pharma said in its World Preview 2018.
Novo Nordisk A/S (ADR) NVO 1.48% launched its Ozempic injection, chemically semaglutide, 0.5 mg or 1 mg as well as Fiasp 100 Units/mL across the U.S. in February. The FDA had approved Ozempic, a glucagon-like peptide 1 agonist, in December. EvaluatePharma estimates Ozempic sales of about $4.41 billion by 2024.

Major Heartaches

On the flipside, some biotechs did experience setbacks in the first half of the year.
Incyte Corporation INCY 0.98% had to halt trials of its lead immunotherapy candidateepacadostat — which was evaluated in combination with Merck & Co., Inc. MRK 1.42%‘s Keytruda for melanoma — after it failed to meet the primary endpoint in a pivotal Phase 3 study. The news triggered a 23-percent downward move in Incyte shares in a single day on April 6.
AbbVie Inc ABBV 1.21% had its share of bad news, as its rovalpituzumab tesirine, or Rova-T, produced disappointing results. The therapy was evaluated in a Phase 2 trial dubbed TRINITY as a third-line treatment for patients with relapsed or refractory small-cell lung cancer demonstrating high DLL3 expression. The company said it would not pursue accelerated approval for Rova-T. The stock fell about 13 percent on the March 22 announcement and is still off from levels reached before the announcement.
Celgene Corporation CELG 1.56% was in for a shock after the FDA issued a “refuse-to-file” letter in response to its NDA filing for ozanimod in patients with relapsing forms of multiple sclerosis.

It’s Raining Deals

M&A in the biotech space picked up momentum after a lull in 2017, with a few multibillion-dollar deals announced in the space. Tax reform freed up free cash flow, and the urge to bolster pipelines prompted companies to explore the M&A route in a bid to reinvigorate sagging top and bottom lines. Some of the noteworthy deals that were announced include:
Japan’s Takeda agreeing to buy Shire PLC (ADR) SHPG 1.35% for $62 billion.
Sanofi SA (ADR) SNY 3.74% acquiring Bioverativ, which develops hemophilia and blood disorder drugs, for $11.6 billion, as well as Belgian biotech company Ablnyx for $4.8 billion.
Celgene buying Juno Therapeutics for $9 billion — and in the process gaining a foothold in the immuno-oncology market through its access to JCAR071, a CD-19 targeted CAR-T therapy in pivotal late-stage trials for relapsed and/or refractory diffuse large B-cell lymphoma. Celgene also bought Impact Biomedicines for up to $7 billion, including potential milestone payments.

A Second Half Preview

Here’s a sneak peek into potential biotech catalysts coming in the second half of 2018.

FDA Approvals

Johnson & Johnson JNJ 1.74%‘s sNDA for its Xarelto vascular dose to reduce the risk of major cardiovascular events in patients with chronic coronary and/or peripheral artery disease, as well as for reducing the risk of acute limb ischemia in patients with peripheral artery disease, is pending before the FDA. The application was submitted in mid-December.
Teva Pharmaceutical Industries Ltd (ADR) ADR TEVA 3.04%‘s BLA for its migraine treatment candidate fremanezumab will come before the FDA, with the agency scheduled to rule on the drug Sept. 16.
Abbvie and Neurocrine Biosciences, Inc. NBIX 0.79% are awaiting the FDA verdict on their NDA for elagolix in endometriosis-associated pain. The PDUFA date is set for the third quarter following a three-month extension of the review period.
Insys Therapeutics Inc INSY 2.09% has a July 28 FDA date and is set to receive the verdict on the company’s sublingual spray formulation of buprenorphine to treat moderate-to-severe acute pain.
DURECT Corporation DRRX 8.28%, which has licensed its schizophrenia candidate RBP-7000 to U.K.-based Indivior, comes under the FDA scanner, with the agency set to rule July 28 on the pipeline candidate. DURECT will yet again be in the spotlight, as Remoxy ER, a drug it licensed to Pain Therapeutics, Inc. PTIE 16.74% has a PDUFA action date of Aug. 7. The odds of the drug clearing the FDA hurdle have worsened after a FDA panel voted against the approval.
SIGA Technologies, Inc. SIGA 2.65%‘s small pox antiviral therapy Tpoxx in an oral formulation faces an FDA decision Aug. 8.
AstraZeneca plc (ADR) AZN 0.27%‘s BLA for moxetumomab pasudotox for treating hairy cell leukemia has a PDUFA date in the third quarter.
Bristol-Myers Squibb Co BMY 1.18%‘s sBLA for Opdivo for treating small-cell lung cancer that has progressed following two or more lines of therapy was granted priority review in mid-April. The application was submitted based on the CheckMate-032 trial.
Eli Lilly And Co LLY 0.13% and Merck await the FDA’s decision on the Keytruda-Alimta combo along with platinum chemotherapy as a first-line treatment for patients with metastatic non-squamous non-small cell lung cancer. The PUDFA action date is set for Sept. 23.
Pfizer Inc. PFE 1.14%‘s dacomitinib, evaluated as a first-line treatment for squamous non-small cell lung cancer with epidermal growth factor receptor-activating mutations, awaits the FDA’s verdict in September.
The FDA is set to rule on Verastem Inc VSTM 1.64%‘s lead product candidate duvelisib Oct. 5. The pipeline candidate is being tested for relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma.

Clinical Trials

Alkermes Plc ALKS 0.58% expects to release top-line results from the ENLIGHTEN-2 study, the second of two key Phase 3 studies for ALKS 3831 for schizophrenia, in the fourth quarter. The company plans to use clinical data from the study for the NDA submission if the study is successful, along with the previously reported data for the ENLIGHTEN-1 study.
Foamix Pharmaceuticals Ltd FOMX 0.79% plans to release top-line results from two Phase 3 pivotal studies for its FMX103 trial of 1.5-percent topical minocycline foam in rosacea early in the fourth quarter. The company will also release top-line data for its FMX-101 Phase 3 acne study in the third quarter.
FibroGen Inc FGEN 1.62% expects to release top-line results from Phase 3 studies supporting its NDA submission for roxadustat in anemia-associated with chronic kidney disease by the end of 2018. The company expects to submit the NDA in the first half of 2019.
Regulus Therapeutics Inc RGLS 1.37% plans to release data from the Phase 1 renal biopsy study of RG-012 to treat Alport syndrome by the end of the year.
OncoSec Medical Inc ONCS will complete enrollment of 23 patients in the first stage of the PISCES/KEYNOTE-695 study evaluating its intratumoral Tavo plus electroporation in combination with intravenous Keytruda in patients with stage III/IV melanoma who are progressing on either Keytruda or Opdivo in the third quarter. The company expects to present top-line results from this study before the end of the year.

Regulatory Submissions

AbbVie announced positive Phase 3 top-line results for its oral JAK1-selective inhibitor upadacitinib in early June. The candidate is being evaluated as a monotherapy in adults with moderate-to-severe rheumatoid arthritis. The company expects the SECLECT-EARLY study, the fifth pivotal study, to -produce results supporting a regulatory filing in the second half of 2018.
Intra-Cellular Therapies Inc ITCI 5.06%, which initiated a rolling submission of its NDA for lumateperone for treating schizophrenia in June, expects to complete the NDA submission by mid-2018. Rolling submission allows a company to submit sections of the NDA when they are complete, rather than waiting until the entire application is finalized.
Posted by at No comments:

Oral Meds Relieve Acute Migraine Attacks


Two oral calcitonin gene-related peptide (CGRP) inhibitors offer rapid relief from acute headache pain and associated migraine symptoms for about 20% of patients, researchers reported here.
One in five people treated with rimegepant in a phase III study reported freedom from pain at 2 hours after a single dose, and nearly 40% reported relief from their most bothersome symptom, usually photophobia. Similar proportions of patients reported improvement after taking ubrogepant.
The findings were presented at the American Headache Society (AHS) annual meeting.
Vascular dysfunction is thought to play a key role in migraine. CGRP is a potent vasodilator, and blocking the peptide or its receptors can prevent or treat migraine without the cardiovascular side effects often seen with triptans. Monoclonal antibodies are being developed for migraine prophylaxis, while small-molecule oral agents are under study for the treatment of acute attacks.
“This morning we’ve heard about seven new molecular entities that are effective in acute or preventive treatment of migraine and a couple novel ways of delivering older drugs. This is truly a remarkable time in our field,” said Richard Lipton, MD, of Albert Einstein College of Medicine in New York City.
For decades triptans have been the most widely prescribed drugs for the acute treatment of migraine, but many patients cannot use them because of cardiovascular contraindications.
“Perhaps a third of people with migraine don’t respond to triptans, 30% to 40% have recurrent attacks, and according to our estimate 3.5 million people have absolute or relative contraindications for triptans among the 40 million people who get migraines,” Lipton said. “Clearly there are unmet needs, and the hope is that ‘gepants’ will address some of those needs.”
Study 302 of Rimegepant
Lipton presented findings from Study 302, a double-blind phase III trial comparing rimegepant, an oral CGRP receptor antagonist, versus placebo for the acute treatment of migraine.
The study included 1,072 patients; nearly 90% were women, and median age was 41. Participants had at least a 1-year history of migraine and had two to eight attacks of moderate to severe intensity per month (median 4.6 attacks); those with chronic migraine (more than 15 headache days per month) were excluded. Patients were allowed to be on stable migraine prevention medication. They reported their most bothersome symptom to be photophobia (58%), nausea (16%), and phonophobia (27%).
Participants were randomly assigned to receive 75 mg rimegepant or placebo to treat a single migraine attack. A total of 543 people were treated in each group (some enrolled patients did not experience attacks during the follow-up period). Rescue medication was permitted at 2 hours if needed.
At 2 hours after treatment, 19.6% of patients in the rimegepant group reported pain freedom, compared with 12.0% in the placebo group (P=0.0006). At the same time point, 37.6% and 25.2%, respectively, reported freedom from their most bothersome symptom (P=0.0001).
Looking at secondary endpoints, the researchers found that more people in the rimegepant arm reported being free of photophobia and phonophobia at 2 hours post-treatment. The proportions reporting pain relief at 2 hours were 58.1% in the rimegepant arm and 42.8% in the placebo arm; 32.6% and 23.4%, respectively, were able to function normally. Fewer patients required rescue medication in the rimegepant arm compared with the placebo arm (21.0% versus 37.0%).
The proportion of patients receiving rimegepant reporting freedom from pain after a single dose with no rescue medication rose over time, from 20% at 2 hours to 48% at 8 hours. Significantly more people in the rimegepant arm reported continued pain freedom, pain relief, and ability to function through 48 hours.
Treatment was generally safe and well tolerated, Lipton said. One patient in the rimegepant arm and two in the placebo arm had serious adverse events — 1.8 and 0.6%, respectively, had treatment-related adverse events. There were no adverse events leading to treatment discontinuation in either group. Elevated liver enzymes are a potential concern with this class of drugs, but no patients had alanine aminotransferase or aspartate transaminase levels that were more than three times the upper limit of normal or bilirubin more than twice the upper limit.
The researchers concluded that rimegepant offers broad and clinically important benefit with a single dose, with an excellent safety profile similar to that of the placebo. Lipton noted that a parallel trial, Study 301, also showed consistent results.
ACHIEVE I Trial of Ubrogepant
David Dodick, MD, of the Mayo Clinic in Phoenix, presented results from ACHIEVE I, a phase III trial evaluating another oral CGRP receptor agonist, ubrogepant.
As previously reported at the American Academy of Neurology annual meeting in April, 19.2% of patients treated with a single 50 mg dose of ubrogepant and 21.2% of those who received 100 mg reported freedom from pain at 2 hours post-treatment, compared with 11.8% of placebo recipients. About 38% in both dose groups were free of their most bothersome symptom at 2 hours, the study found.
Various secondary endpoints also favored ubrogepant over placebo. A third of patients reported satisfaction with ubrogepant at 2 hours, rising to more than 60% at 24 hours. Like rimegepant, ubrogepant was generally safe and well tolerated. Dodick said that “nearly identical” results were seen in the related ACHIEVE II trial.
These pivotal results support the approval of rimegepant and ubrogepant for the acute treatment of migraine, he said. Biohaven Pharmaceuticals and Allergan have indicated that they plan to file New Drug Applications for the agents in 2019.
Commenting on these two drugs and others described at the same session, moderator Andrew Charles, MD, of the David Geffen School of Medicine at UCLA, told MedPage Today, “How they sort out in comparison remains to be seen, but it shows that the target [CGRP] is an important one and the medications that are going after this target are all working.”
The rimegepant study was funded by Biohaven Pharmaceuticals.
The ubrogepant study was funded by Allergan.
Lipton and Dodick both reported relationships with numerous companies active in migraine drug development.
Posted by at No comments:

Migraine Patterns Often Change During Menopause


About 60% of women with migraine experience changing headache patterns around the menopause transition, with a majority of those reporting greater frequency or worsening intensity, according to research presented here.
Migraine changes were most likely during the post-menopausal period — reported by 43% of study participants — and were associated with greater changes in hormone levels.
The results were presented at the American Headache Society annual meeting.
Women make up three-quarters of all patients with migraine. Past research has shown that migraine patterns may change over the course of the normal menstrual cycle, as well as during pregnancy or after giving birth, suggesting that hormonal levels and patterns play a role. Although some prior studies have reported an increase in headaches during peri-menopause, there are few data about the changing course of headaches in women with pre-existing migraine as they go through the menopause transition.
“The evolution and character of migraine during the peri-menopause has not received as much attention as it deserves, so it’s nice to see this study. The study results are consistent with the common clinical impression that the peri-menopausal transition is a time when migraine headaches often change in character,” Elizabeth Loder, MD, MPH, chief of neurology at Brigham and Women’s Hospital in Boston, told MedPage Today.
Yu-Chen Cheng of Massachusetts General Hospital in Boston presented findings from a retrospective study of changing migraine patterns among women of peri-menopausal and menopausal age, 40 to 60 years.
The study used data from the Research Patient Database Registry of Partners HealthCare, a not-for-profit system in the Boston area that includes a managed care organization, hospitals, community health centers, and home care.
The analysis included 60 women with data on pre-existing migraines prior to menopause who had available MRI reports and medical records with information on estradiol and follicle-stimulating hormone (FSH) levels. Most (80%) were white, the median age at menopause was approximately 47 years, and two thirds used estrogen-based hormone replacement therapy (HRT). There were no notable demographic differences between the group with migraine changes and the group without changes, Cheng said.
Of these women, 35 (58.3%) reported migraine changes while 25 (41.7%) said they did not have changes. Within the first group, 60.0% reported greater frequency or intensity, 28.6% said the characteristics of their headaches changed, and 2.8% reported both.
Migraine changes were most likely to occur post-menopause, or after the final menstrual period (42.9%). This was followed by changes during peri-menopause, defined as either clinical indications such as irregular periods or climacteric symptoms, or 1 year before the final menstrual period (31.4%). Changes were least likely to occur pre-menopause, defined as having regular periods (14.3%).
Women who experienced migraine changes experienced greater hormonal changes than those who did not. Women with migraine changes started with higher levels of estradiol before menopause (median 52.6 versus 29.0 pg/mL) and saw a larger drop, as well as having lower pre-menopause FSH levels (median 13.53 versus 38.58 U/L) and a greater rise. Most of these differences, however, did not reach statistical significance.
Brain imaging showed that a majority of women with and without migraine changes had normal MRI findings (68.6% and 56.0%, respectively). Women without migraine changes were numerically more likely to have pituitary abnormalities and white matter lesions, but again the differences were not statistically significant.
While the underlying mechanism for migraine change during menopause remains unclear, Cheng said, previous research indicates that declining estrogen levels stimulate migraine attacks in the late luteal phase, and migraineurs have a faster decrease in estrogen than women without migraine. The steep decline in estrogen may trigger migraine changes during the menopause transition, she suggested.
“This is an important but underestimated and undermanaged issue, and more awareness and better treatment are needed,” Cheng and colleagues concluded.
Asked about the potential of HRT for managing migraines during the menopause transition, Cheng noted that women with and without migraine changes in this analysis had similar rates of HRT use, and said that studies have produced mixed results about whether HRT triggers migraine or is beneficial.
“It could be beneficial in the future to use hormone therapy for these patients,” Cheng told MedPage Today.
Loder cautioned that the women in this study may not be representative of all peri-menopausal women with migraine.
“It is possible that some of the testing and imaging may have been done in response to changes in migraine status; thus, requiring the presence of tests and imaging in order to include patients in the study may have inadvertently selected a group in whom pituitary abnormalities or clinical worsening are more likely. Further prospective studies would be needed to verify this observation,” said Loder, who was not involved in the study.
Lauren Green, DO, RD, of the Keck School of Medicine at the University of Southern California, said that brain imaging may be a useful tool for managing women with headaches during the menopause transition.
“In neurology, we are always concerned about secondary headaches versus the more common primary headache such as migraine,” Green told MedPage Today. “This study supports performing MRI imaging on peri-menopausal and menopausal women with a distinctive change in their typical headache presentation.”
Cheng, Loder, and Green made no relevant disclosures.
Posted by at No comments:

BioMarin partners with local senior center for new lab expansion project

BioMarin is proposing three new buildings at the former PG&E site, with two for R&D and offices, and one combining housing and a senior center. (Pixabay)
Posted by at No comments:

Controlling CRISPR and gene therapy with an amino acid switch


Gene editing and gene therapy have a range of potential applications, from editing out disease-causing mutations to treating spinal cord injuries. But the ability to control these treatments is a key concern, as they may stay switched on after they have had their intended effect, causing unwanted side effects. Scientists from the University of Bath and Cardiff University have created a switch that controls protein expression in cultured cells and mouse embryos and could one day be used in human gene therapies, the researchers believe.
The team tested the switch, an amino acid called BOC, in mice that had been genetically engineered to glow green under ultraviolet light. They used a method called genetic code expansion to create mouse embryos whose fluorescence gene had been edited out—but only in the presence of BOC. Edited embryos that were exposed to BOC were able to develop into mice that did not glow, but those not exposed to BOC remained green.
BOC is cheap and nontoxic and “should work in any protein in any species,” the researchers said in a statement. Many of the switch’s most immediate applications are environment-related—it could be used to keep the mosquito population down by propagating a gene that makes them infertile, they said. But it could also be used to control Cas9 proteins used in CRISPR-Cas9 gene editing. The study is published in Scientific Reports.
Adding switches to gene therapies is not a new idea, but current approaches have kinks that need to be addressed before they can be used in humans. Researchers from King’s College, for example, are working to treat spinal cord injuries using a gene therapy with an antibiotic-based “off” switch. The treatment triggers production of an enzyme that breaks down scar tissue, allowing neurons to regenerate. The antibiotic doxycyline is delivered after treatment to trigger the “off” switch.
While the treatment restored some hand function to rats that had suffered a spinal cord injury, a small portion of the targeted gene remained active even after the therapy had been switched off. The King’s team is working to shut off the gene completely and move into trials in larger animals.
As for gene editing, several approaches are in development to address the possibility of runaway editing. A team from the Salk Institute devised an “epigenetic CRISPR-Cas9” tool that edits DNA without cutting it as traditional CRISPR does, breaking the DNA and making it vulnerable to off-target mutations. The system is based on dead, or inactivated, Cas9. And the Broad Institute is using a CRISPR-based system dubbed REPAIR to edit RNA and bring about reversible changes in DNA. CRISPR pioneer Feng Zhang and colleague David Liu launched their startup, Beam Therapeutics, in May, which will use REPAIR and other technologies to edit nucleotide bases and correct point mutations.
Others are also focusing on enzymes to make CRISPR safer. Scientists at the Institute of Bioorganic Chemistry in Poland used a variant of Cas9 that cuts one strand of DNA rather than both strands.
The U.K. team sees the potential for BOC in several scientific and clinical settings. In addition to controlling gene therapy, the switch could be used to switch on and off proteins in cells to study aging, or to enhance regenerative medicine. The researchers now plan to “iron out wrinkles” in the system before testing it in broader applications, they said in a statement.
Posted by at No comments:

Beleave Unit Agrees to Lease Land in Colombia


Beleave Inc. (CSE: BE) (OTCQX: BLEVF) (“Beleave” or the “Company“) today announced that its Colombian subsidiary, Procannmed S.A.S. (“Procannmed“) has reached a land-lease agreement that will allow for the development and expansion of Procannmed’s cultivation of cannabis for sale and extraction purposes.

Under the agreement, Procannmed will lease up to 27 hectares (roughly 67 acres, or 2.9 million sq ft) of private land for a nominal monthly fee of $100 USD per hectare. The term of the agreement is for five years, with an option to renew for an additional five years.
Last month, Beleave announced it had acquired 51% of Procannmed for a combination of cash and Beleave common shares. The transaction stemmed from a lengthy due diligence process in which members of the Beleave team visited Colombia to speak with Procannmed representatives and various government and industry-related parties. This land deal is a direct result of those meetings and subsequent acquisition.
“This is an example of how we’re creating value beyond the immediate benefits of our growing and distribution activities,” says Beleave CEO, Andrew Wnek. “Now we can all look forward to the next stages of project development, and the tremendous potential this land offers to create value for shareholders.”
Posted by at No comments:

Bristol-Myers seeking buyer for French OTC drug unit


Bristol-Myers (BMY) has hired Deutsche Bank (DB) and Jefferies (JEF) to find a buyer for its French over-the-counter drugs business, which could be valued at over 1 billion euros, according to Reuters, citing sources familiar with the matter
Posted by at No comments:
Subscribe to: Posts (Atom)