wrong.- Northwest Biotherapeutics, Inc. (NWBO), a biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, announced today the pricing of an underwritten public offering of 4,895,834 units at a public offering price of $4.80 per unit, resulting in gross proceeds of $23,500,000. Each unit consists of one share of common stock, and a warrant to purchase 0.5 shares of common stock at an exercise price of $6.00 per share.
Sentiment: Strong Buy
THE LEUKEMIA & LYMPHOMA SOCIETY APPLAUDS FDA'S APPROVAL OF IBRUTINIB
THE LEUKEMIA & LYMPHOMA SOCIETY APPLAUDS FDA'S APPROVAL OF IBRUTINIB FOR CERTAIN PATIENTS WITH MANTLE CELL LYMPHOMA
Ibrutinib becomes second drug with 'breakthrough therapy designation' approved by FDA
WHITE PLAINS, N.Y., Nov. 13, 2013 /PRNewswire/ -- Today's U.S. Food and Drug Administration (FDA) approval of ibrutinib to treat patients with mantle cell lymphoma (MCL) is a significant advance for patients with this blood cancer. It was approved as a single agent for treatment of patients with MCL who have received at least one prior therapy.
Ibrutinib is the second drug with "breakthrough therapy designation" to receive FDA approval. Ibrutinib is a therapy that targets an enzyme, Bruton's tyrosine kinase (BTK), which promotes growth of B-cell cancers, including MCL, chronic lymphocytic leukemia (CLL), Waldenstrom's macroglobulinemia (WM), follicular lymphoma, diffuse large B-cell lymphoma, hairy cell leukemia (HCL) and multiple myeloma.
"After the FDA earlier this year designated ibrutinib as a breakthrough therapy for patients with certain forms of blood cancers, we were all hopeful that it was only a matter of time before the therapy was approved to treat these patients, who have few good treatment options," said John Walter, president and CEO of The Leukemia & Lymphoma Society (LLS).
LLS is eager to learn the outcome of FDA's ongoing review of ibrutinib for patients with chronic lymphocytic leukemia (CLL) and Waldenstrom's macroglobulinemia (WM).
"Many patients with MCL and other B-cell cancers do not respond well to standard therapies and new treatments such as ibrutinib are urgently needed," said Louis J. DeGennaro, Ph.D., LLS chief mission officer. "LLS exists to find cures and ensure access to treatments for blood cancer patients, and any new advance that brings the potential to help save more lives is good news."
LLS funding has supported clinical trials and laboratory s
November 8, 2013
07:50 EDT PCYC Pharmacyclics price target raised to $132 from $123 at RW Baird
Baird raised its price target on Pharmacyclics following its post clinical updates. The firm believes its Phase 3 RESONATE study for ibrutinib will provide a basis for a full approval. Shares are Outperform rated.
Sentiment: Strong Buy
Pharmacyclics is a clinical-stage biopharmaceutical company focused on discovering and developing small-molecule drugs for oncology and autoimmune diseases. Its primary drug candidate is Ibrutinib, the first in class of a new wave of oral agents ready to transform the treatment of white blood cell malignancies, including leukemia, lymphoma, and myeloma.Current treatments for blood cancers include Genentech’s Rituxan, which is now owned by Biogen Idec BIIB -0.98%, and Celgene CELG -1.77%‘s Revlimid. These drugs both achieved “blockbuster” status with sales in the billions of dollars. Analysts believe that PCYC’s ibrutinib has the same or greater potential because it could surpass those drugs in terms of efficacy and safety. It also doesn’t hurt that Johnson & Johnson JNJ +0.43% is a partner.
PCYC shares have more than doubled this year, from $60 to over $140 in early October. In July, Pharmacyclics submitted its new drug application (NDA) for Ibrutinib and by September began presenting positive data surrounding Ibrutinib’s market potential and pipeline strategy including the development of the next-generation BTK inhibitor for autoimmune disease.They describe their drug’s function as “a selective, irreversible inhibitor of Bruton’s tyrosine kinase (BTK), a critical signaling kinase in the B-cell receptor pathway for tumor cell survival and proliferation.”
Management indicated on September 12 at a conference that Ibrutinib is on track for approval in late February, 2014 and they said the commercial force is built out and J&J is supplementing the 60+ PCYC U.S. sales force.
Late to the Game
During the week of September 23, at least three investment banking firms initiated coverage of PCYC as follows: William Blair initiated with an Outperform rating and a $143 price target. Deutsche Bank initiated with a buy rating and a $170 price target. JPMorgan initiated with an overweight rating and a $142 price target. Finally, on October 4, Wells Fargo joined the party, initiating coverage with a $155-160 valuation range.
One group of analysts who were early on the prospects for PCYC reside at Wedbush. Gregory R. Wade, David M. Nierengarten, and Christopher N. Marai — all Ph.Ds — have been covering PCYC for over a year. In March, when the stock was trading $86, they raised their 12-month price target to $165 from $110.
Earlier this month, they put out a note about competition from Gilead Sciences (GILD – Analyst Report). The analysts wanted to address the success of a phase 3 study of Idelalisib (I), the PI-3 kinase inhibitor acquired with GILD’s Calistoga acquisition. Their conclusion was that Idelalisib should not be seen as a significant competitor to Ibrutinib and they reiterated their Outperform rating on PCYC shares, also on their best ideas list. They’ve had investors in PCYC since June of 2012 when it was trading $34 and they raised their price target to $55 from $40.
PCYC has been either a Zacks Rank #1 (Strong Buy) or rank of #2 since August 3rd and I expect it to at least maintain a #3 Rank as the company gets closer to surviving all of its FDA gauntlets for Ibrutinib . As more analysts get on this bandwagon, more refined sales estimates and drug launch costs will filter into a tighter dispersion of revenue and EPS estimates.
Peak sales projections for Ibrutinib are now in the range of $6 to $9 billion.
As with all clinical-stage biopharma companies, investors are rewarded at various stages of clinical success, but sometimes the waiting periods and price volatility in between those milestones can be long and trying. That’s why it is crucial to keep an eye on the analyst estimates for sales and (eventual) profits, and on the stock price.
Finding a good entry point can mean the difference between having a “margin of safety” and nursing double-digit losses until the stock comes back. Aggressive biotech investors and traders should consider PCYC on dips below $120 like we are seeing on Thursday.
Sentiment: Strong Buy
Sound like doctors would.Medical experts say every year about 12,000 patients in the U.S. are diagnosed with chronic lymphocytic leukemia. But a new drug has shown promise for patients who've lost all hope of beating the disease.
It's the simple things, like enjoying the outdoors and taking family vacations that 73-year-old Dennis Hickey can look forward to once again.
"I can do my job, I sell houses,” says Dennis Hickey who has chronic lymphocytic leukemia. “I can enjoy the grandkids."
Dennis has chronic lymphocytic leukemia, or CLL, a common and deadly form of leukemia affecting older adults.
"The prognosis was not good," says Dennis.
With six months to live, Dennis got to take an experimental drug called ibrutinib as part of a clinical trial for CLL patients.
"We've seen a drug come into the clinic that has really helped patients with CLL and related diseases that have been at the end of their life," explains Dr. John C. Byrd, MD, D. Warren Brown Chair of Leukemia Research at the Ohio State University Comprehensive Cancer Center.
The drug works by targeting the protein in CLL cells. Without the protein, the cancer can't grow.
Doctors say 90-percent of patients have had success with ibrutinib and side effects are minimal compared to chemotherapy.
"Patients tolerate it very, very well,” says Dr. Byrd. “Many patients will say they feel like they did before they had CLL."
Researchers say ibrutinib's a game changer. Dennis Hickey says it's a life saver.
"I'm still here,” explains Dennis. “I look, I look back to it and say boy, I've been blessed, and I'm so thankful."
Researchers say ibrutinib is not a cure, but if patients follow treatment, they can manage CLL the same way they would manage diabetes or high blood pressure. The drug is expected to be approved by the FDA
Sentiment: Strong Buy
Abstracts selected for the 2013 ASH Annual Meeting will be available on Thursday, November 7, at 9:00 a.m. EST. The late-breaking abstracts submission site will open October 22 and will close October 29, 2013.
Sentiment: Strong Buy
The 17% with significant pneumonia is more worrisome to me than the 1 in 4 with elevated liver enzymes. That usually resolves with stopping meds, and one can usually restart at a lower level without recurrent liver issues, but pneumonia can be fatal in CLL.This begs the question : Is Idelalisib likely to be a contributor to other infections (as to yet unknown) as happened with Ofatumumab after it had been in use for a while ?
Sentiment: Strong Buy
Late to the party plus it's patients receiving idelalisib plus rituximab compared to those receiving rituximab alone. August 29, 2013
New Drug Application Filing for Ibrutinib Accepted in Two B-cell Malignancies by the U.S. FDA
Priority Review Granted
SUNNYVALE, Calif., Aug. 29, 2013 /PRNewswire/ -- Pharmacyclics, Inc. (Nasdaq: PCYC) today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing its New Drug Application (NDA) for the investigational oral Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, for two B-cell malignancy indications: previously treated mantle cell lymphoma (MCL) and previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). On June 28, 2013 Pharmacyclics submitted a New Drug Application (NDA) under section 505(b) of the Food, Drug & Cosmetic Act for ibrutinib. On Aug 27, 2013 the FDA notified Pharmacyclics that they have completed their filing review and determined that the application is sufficiently complete to permit a substantive review. The FDA's acceptance of the NDA triggers a $75 million milestone payment to Pharmacyclics under its Collaboration Agreement with Janssen Biotech Inc.
"We are very excited to have received the official FDA acceptance of our first NDA filing for ibrutinib," said Dr. Urte Gayko, Senior Vice President of Global Regulatory Affairs, Pharmacyclics. "We look forward to continuing to work with the FDA as they complete their review of the ibrutinib application which includes the new Breakthrough Therapy Designation process."
About CLL / SLL
CLL, a B-cell malignancy, is a slow-growing blood cancer of the white blood cells (lymphocytes), most commonly from B-cells. CLL is the second most common adult leukemia. Approximately 16,000 patients in the US are diagnosed each year with CLL. The prevalence of CLL is approximately 113,000 in the U.S. CLL is a chronic disease that predominantly occurs in the elderly with a five-year survival of approximately 82 percent.1 Patients commonly receive multiple lines of treatment over the course of their disease. When cancer cells are located mostly in the lymph nodes, the disease is called SLL. CLL and SLL are considered to be different manifestations of the same underlying disease; they share similarities in signs and symptoms, genetic features, disease progression and treatment.
About Mantle Cell Lymphoma
MCL is a B-cell malignancy, an aggressive type of B-cell non-Hodgkin lymphoma (NHL) that usually occurs in older adults.2 The disease typically begins in the lymph nodes, but can spread to other tissues, such as bone marrow, liver, and spleen3. Patients typically survive an average of five years.4 In the U.S., there are approximately 2,500 new cases of MCL each year and a prevalence of approximately 10,000 (Decision Resources 2012).
Sentiment: Strong Buy
THURSDAY, OCTOBER 3, 2013
News from the Infusion Center: Taking a Normal CBC for Granted
I went seven weeks between blood draws and my infusion of IVIG to coat and protect my platelets.
The CBC is usually reported back within minutes at the oncology suite.
The fact that it was all basically normal is not the news.
What is new is that I didn't ask to see it immediately. My oncologist didn't review it before walking in the room.
Both of us have grown to expect that it would be boring, and boring it was.
Hgb. which goes up and down for no reason was back to a normal 14.2.
Platelets were staying high and dry at 381,000.
My ALC was only about 1.0.
Blood chemistries were all good too except for a slightly low protein level. Uric acid was nice and low at 5.6 despite being on cyclosporin, infamous for causing accelerated gout. My LDH was stable and normal. Still waiting for my immunoglobulins.
It wasn't all that long ago that I dreaded these lab tests and waited anxiously to see if the results would land me an unplanned visit to an infusion chair or an urgent hospital admission.
How times have changed.
Thank you ibrutinib.
Now I will go eight weeks between visits for IVIG. It was needed every two weeks for years. My veins and I are truly living in gratitude.
Sentiment: Strong Buy
The truth for that guy Kloper .Liquidity and Capital Resources
Our principal sources of working capital have been private and public equity financings as well as proceeds from collaborative research and development agreements. At March 31, 2013 , we had $511,247,000 in cash, cash equivalents and marketable securities.No counting the $75,000,000 for the FDA accepted for filing its new drug application for treating two types of blood cancer.which triggers a $75 million payment to the company from Johnson & Johnson’s FDA notified the company on Aug. 27 2013.
Sentiment: Strong Buy
All signs point to the imminent FDA approval of ibrutinib, the once-daily oral Bruton tyrosine kinase (BTK) inhibitor with impressive efficacy in the treatment of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). At press time, the FDA was reviewing a New Drug Application (NDA) submitted by the drug’s manufacturer, Pharmacyclics, Inc., on July 10, 2013.
The submission comes on the heels of findings published in The New England Journal of Medicine (NEJM) showing a 71% clinical response rate in difficult-to-treat CLL patients (2013;369:32-42).
The results have elicited nearly unanimous enthusiasm from the hematology/oncology community, including Nicole Lamanna, MD, an associate clinical professor of medicine in the Hematologic Malignancies Section of the Hematology/Oncology Division at Columbia University Medical Center, in New York City.
“This is a huge kudos for the field,” said Dr. Lamanna, who was not involved in research on the drug. “There is little doubt in most of our minds that ibrutinib will be used in some fashion as first-line therapy for CLL, with the potential of sparing some patients a number of treatments that otherwise might be too toxic.”
Along with previously published findings, the NEJM results have impelled the FDA to also apply three Breakthrough Drug Designations to ibrutinib and to place it on a fast track for approval. In an email to Pharmacy Practice News, the FDA would not comment on the timing of the drug’s approval.
The NEJM data, initially presented at last year’s American Society of Hematology (ASH) annual meeting in Atlanta, included outcomes from 85 CLL patients with refractory or relapsed disease, who were randomized to receive 420 or 840 mg daily of the drug. The participants had undergone a median of four prior therapies. Of the patients, 33% had 17p deletions and 36% had 11p deletions; both deletions predict poor treatment response. Patients were a median 66 years of age and were followed for a median of 21 months.
Led by John Byrd, MD, from the Division of Hematology in the Department of Internal Medicine at Ohio State University in Columbus, the researchers reported that 71% of patients in either group experienced a clinical response. Since most had some evidence of continuing disease, their response was considered partial. The estimated progression-free survival and overall survival rates were 75% and 83%, respectively, over 26 months, and the likelihood of response was independent of clinical and patient characteristics.
The investigators found that 78% of the partial responders experienced transient lymphocytosis in the early part of treatment. However, an additional 20% in the low-dose group and 15% in the higher-dose group had persistent lymphocytosis despite significant reductions in tumor size, and therefore were classified as nodal partial responders.
What Can Pharmacists Expect?
Informing physicians of the potential for transient lymphocytosis early in the course of treatment will be a key role for pharmacists, said Lindsay Hladnik, PharmD, BCOP, a clinical pharmacist for Hematologic Malignancies/Stem Cell Transplantation at Barnes-Jewish Hospital in St. Louis, Mo. “It will be important for them to know that this is likely due to the drug’s mechanism of action and not to disease progression,” said Dr. Hladnik, who was not involved in the research.
According to the NEJM study, the most common adverse events (AEs) were grade 1-2 diarrhea (47% of both groups), grade 1-2 fatigue (28%) and grade 1-2 upper respiratory tract infections (33%). Grade 3-4 AEs included pneumonia (12%), dehydration (6%), neutropenia (15%), pyrexia (5%), hypertension (5%) and sinusitis (5%). Most infections occurred early in the course of treatment.
Two patients in the 420 mg group and four patients in the 840 mg group discontinued treatment because of AEs, the investigators reported.
Robert C. Wolf, PharmD, the hematology/oncology pharmacotherapy coordinator and program director of the Pharmacy Practice Residency in Oncology at Mayo Clinic College of Medicine in Rochester, Minn., said ibrutinib’s “specific role and place in therapy will be better defined over the ensuing months to years as clinical trial results evolve.” Pharmacists can expect to provide the usual range of care to patients receiving ibrutinib, said Dr. Wolf, who has not been involved in research on the drug.
“While not necessarily unique to ibrutinib, issues of access, adherence, follow-up for efficacy and safety, drug interactions and affordability will need to be addressed,” he said.
Potential Accessibility Implications of Long-Term Treatment
Dr. Hladnik added that having knowledge of the available patient access programs for ibrutinib and being able to direct physicians to these resources will be critical, “especially since patients will take ibrutinib continuously until disease progression or unacceptable toxicity."
“This could potentially be a very expensive treatment and patient access could become a real issue,” Dr. Hladnik added. “Hopefully, there will be good patient access programs in place.”
For her part, Dr. Lamanna said, “I wonder about the long-term unexpected toxicity with ibrutinib, as this will likely be prolonged therapy. Also, will ibrutinib need to be used indefinitely—as it is currently administered in clinical trials—if patients who respond eventually achieve complete responses or MRD [minimal residual disease] negativity?” she asked.
At press time, Dr. Hladnik said she was not aware of any information on any ibrutinib dosing adjustments, drug–drug and drug–food interactions and adverse-event monitoring. However, she said ibrutinib appeared to be straightforward to administer and manage.
“The once-daily oral dosing will definitely help with patient compliance, although we could play a key role in verifying patient compliance and evaluating and managing any adverse events, like diarrhea, so that patients can stay on the medication,” she noted.
Dr. Hladnik echoed the enthusiasm shared by the broader hematology/oncology community regarding the drug’s efficacy and safety, but noted that findings to date have been from Phase 1 or 2 studies, including the Phase 1b-2 NEJM study. “When it comes to oncology drugs, you can get an agent approved based on Phase 2 studies if there is an unmet clinical need, but outcomes can be different once it’s studied in Phase 3 studies,” she cautioned.
At press time, seven of the 31 registered clinical trials of ibrutinib were Phase 3 studies. A number of the head-to-head trials among these studies are examining use of ibrutinib in combination with other established treatments and for a range of B-cell leukemias.
Dr. Lamanna said she hopes findings on combination treatment with ibrutinib will reveal a further increase beyond the already impressive clinical response rates. She is awaiting updated findings slated for presentation at this year’s ASH annual meeting and at the International Workshop on CLL in Germany, where she expects favorable results on the durability of CLL clinical response with ibrutinib.
“As more data on this drug from ongoing clinical investigation emerges,” Dr. Lamanna said, “lots of exciting new questions in terms of how best to use the drug will, hopefully, be answered.”
Dr. Byrd reported receiving research funding from Pharmacyclics and Janssen. Drs. Wolf, Lamanna, Hladnik and Andritsos reported no conflicts of interest.
Pharmacyclics: Ibrutinib Appears to Have Potential of Becoming SOC in Multiple B-cells Cancers, Benign Safety and Tolerability Profile Shown in Clinical Trials May Expand CLL Treatment into Currently Untreated Patients
Pharmacyclics hosted a recap of its data at ASH and provided an update on development plans moving ibrutinib forward in MCL and CLL registrational trials. We also met with management to better under the company's thinking in terms of developmental strategy. Here, we review the company’s development plans and discuss the data update on mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL).
We remain enthusiastic regarding ibrutinib's potential to become the standard of care for multiple B-cells cancers including CLL, MCL, follicular lymphoma, and the ABC subtype of DLBCL. We believe ibrutinib's benign safety and tolerability profile opens the possibility to expand treatment to currently untreated patients and added to standard of care regimens in a variety of B-cell cancers. We are excited regarding the prospects of this agent. We also see competition emerging from other targeted agents such as Infinity's IPI-145, Roche/Abbot's ABT-199, and Celgene's CC-292.
MCL responses are durable and, impressively, continue to convert to CRs: The Company reported a 68% response rate with a 22% complete response rate with a 13.9 month estimated PFS. We are impressed by the conversion of the partial responses (PRs) to complete responses (CRs). Of the 51 patients that were reported at least year's ASH, the CR rate increased to 39% from 16%.
PCYC is evaluating ibrutinib in two potentially registrational MCL trials. The SPARK phase II single arm trial is enrolling relapsed/refractory RRMCL patients and is evaluating ibrutinib on response rate. We expect this trial to serve as the basis for accelerated approval in the U.S. The second trial is the phase III RAY trial comparing ibrutinib to temsirolimus (Torisel) in RRMCL. We expect the SPARK trial to readout in 2H13 and the RAY trial to readout in mid-2014.
Ibrutinib struggles to show a response in multiple myeloma. Ibrutinib managed to show an unconfirmed response as a monotherapy in multiple myeloma (MM), and physicians were allowed to add dexamethasone (dex) to ibrutinib in progressing patients. Dex/ibrutinib showed a partial response. Another patient had an unconfirmed response on dexamethasone monotherapy. Dexamethasone is an active drug, and investigators at ASH told us that they expect a 10%- 20% response with dex alone in patients with the baseline characteristics in the trial. Therefore, the response could have been due to dex alone, and we need more data before we are comfortable concluding that the ibrutinib has activity in MM.
Ibrutinib continues to show activity in certain subsets of DLBCL: Investigators reported data similar to the data in the ASH abstract showing an impressive response in ABC-DLBCL with a 41% response but only a 5% response rate in GCB- DLBCL. Investigators provided additional insights into the activity of ibrutinib and identified specific mutations that confer resistance to ibrutinib. Patients with CARD11 (0/4 responded) and with MYD88 plus wild-type CD79B (0/5 responded) mutations failed to respond. 71% of patients with CD79B mutations responded. This pattern of resistance is consistent with what we expect from BTK's position upstream of CARD11 in BCR signaling pathway, MYD88 activates IKK through a separate signaling pathway to the BCR pathway, so we would not expect an MYD88 activating mutation tumor cancer to respond to BTK inhibition. CD79B interacts with BCR upstream of BTK, and as we expect, CD79B mutations are sensitive to ibrutinib's inhibition of BTK. These findings suggest identifying BCR signaling mutations would provide an effective method to identify DLBCL responders.
We are very interested to see DLBCL results from a phase I study evaluating ibrutinib with R-CHOP in 2013. At the ASH DLBCL presentation, the investigator expressed an interest to evaluate ibrutinib in combination with front-line therapies such as R-CHOP. PCYC’s partner is currently evaluating ibrutinib in combination with R-CHOP, and we expect updates on this trial within the next twelve months.
Ibrutinib continues to show an extremely durable response in treatment-naive CLL with a 96% PFS at 26 months; the company provided an update on its registrational plans. PCYC along with its partner Janssen announced three potentially registrational monotherapy ibrutinib trials in CLL: newly-diagnosed elderly RESONATE-2, R/R CLL RESONATE, and 17p deletion R/R CLL RESONATE-17p trials. The company is also evaluating ibrutinib in combination with bendamustine and Rituxan (BR) versus BR in the Phase III HELIOS trial. We also expect the company to start
another phase III trial evaluating ibrutinib combos in newly diagnosed patients that are eligible for chemotherapy in 2013.
We also expect ibrutinib to move forward in combination first-line trials for patients that can tolerate chemotherapy (non- elderly). Experts at the PCYC investor meeting said they would like to see an ibrutinib plus Rituxan combination tested against chemotherapy. The ECOG is planning the trial and it is currently considering a three arm trial with IR, FCR-I, and FCR as the comparator. We expect this trial to start in 2013.
We expect ibrutinib's benign safety and tolerability profile may expand CLL treatment into currently untreated patients. Management suggested ibrutinib may provide a compelling option for the "watchful waiting" untreated patients. We asked whether penetration into early patients would require a lower price point, and management emphatically said that these patients have a potentially fatal disease and expects the market to be price insensitive. We believe that is not always the case as with Dendreon's Provenge, but in ibrutinib's case, we largely agree with management given the drugs impressive results.
Source: Stifel Nicolaus/Sendek, December 12, 2012 Oncology Indication: Hematologic Keyword: Market Overview
Sentiment: Strong Buy