On February 22, 2016 PDL BioPharma, Inc. (PDL) (NASDAQ: PDLI) reported financial results for the fourth quarter and twelve months ended December 31, 2015 (Press release, PDL BioPharma, FEB 22, 2016, View Source [SID:1234509142]).

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Total revenues in 2015 increased two percent to $590.4 million from $581.2 million in 2014. Revenues for the year ended December 31, 2015 included $485.2 million in royalties from PDL’s licensees to the Queen et al. patents, $68.4 million in net royalty payments from acquired royalty rights and a change in fair value of the royalty rights assets, which included approximately $43.4 million in net cash royalty payments, $36.2 million in interest revenue from notes receivable debt financings to late-stage healthcare companies, and $0.7 million in realized gains from the sale of PDL’s investment in AxoGen Inc. common stock. During the years ended December 31, 2015 and 2014, our Queen et al. royalty revenues consisted of royalties and maintenance fees earned on sales of products under license agreements associated with our Queen et al. patents. During the years ended December 31, 2015 and 2014, royalty rights – change in fair value consisted of revenues associated with the change in estimated fair value of our royalty right assets, primarily Depomed, Inc., The Regents of the University of Michigan, Viscogliosi Brothers, LLC, ARIAD Pharmaceuticals Inc. and AcelRx Pharmaceuticals, Inc. The full year 2015 revenue growth over the full year 2014 is driven by increased sales of Perjeta, Xolair, and Kadcyla by PDL’s licensees, an increase in the estimated fair value of the acquired royalty rights from the Company’s purchase of Depomed’s diabetes-related royalties, as well as a foreign exchange gain and lower rebate paid to Novartis AG for Lucentis , partially offset by decreased interest revenues due to the early payoff of the AxoGen and Durata Therapeutics, Inc. notes receivables.

Total revenues for the fourth quarter of 2015 increased 52 percent, to $178.1 million from $117.1 million in the fourth quarter of 2014. Revenues for the fourth quarter of 2015 included $121.2 million in royalty payments from PDL’s licensees to the Queen et al. patents, $49.1 million in net royalty payments from acquired royalty rights and a change in fair value of the royalty rights assets, which included approximately $34.4 million in net cash royalty payments, $7.6 million in interest revenue from notes receivable debt financings to late-stage healthcare companies, and $0.1 million in realized gains from the sale of PDL’s investment in AxoGen common stock. The fourth quarter of 2015 revenue growth over the fourth quarter of 2014 is driven by the change in estimated fair value of our royalty right assets, primarily Depomed, Inc.

Operating expenses in 2015 were $40.1 million, compared with $34.9 million in 2014. Operating expenses in the fourth quarter of 2014 were $16.5 million, compared with $17.7 million in 2014. The increase in operating expenses for the year ended December 31, 2015, when compared to the year ended December 31, 2014, was a result of total restructuring costs of $7.9 million in connection with the LENSAR notes receivable extinguishment, which is comprised of a loss on extinguishment of notes receivable of $4.0 million primarily related to a lower estimated fair value of the ALPHAEON Class A common stock, and additional general and administrative expenses of $3.9 million for closing and legal fees related to the LENSAR notes receivable restructuring, and other legal expenses mostly related to $1.2 million in funding the ongoing operation management of Wellstat Diagnostics, partially offset by a decrease in professional services from asset acquisition expenses. The decrease in operating expenses for the quarter ended December 31, 2015, when compared to the quarter ended December 31, 2014, was a result of a decrease in professional services from asset acquisition expenses and a decrease in compensation related expenses, partially offset by the LENSAR restructuring loss and other closing fees, and an increase for legal expenses mostly related to Wellstat ongoing operation management.

Net income in 2015 was $332.8 million, or $2.03 per diluted share as compared with net income in 2014 of $322.2 million, or $1.86 per diluted share. Net income for the fourth quarter of 2015 was $100.6 million, or $0.61 per diluted share, as compared with net income of $55.1 million in the same period of 2014, or $0.32 per diluted share.

Net cash provided by operating activities in 2015 was $301.5 million, compared with $292.3 million in the same period in 2014. PDL had cash, cash equivalents and short-term investments of $220.4 million and $293.7 million at December 31, 2015 and 2014, respectively. The decrease was primarily attributable to the extinguishment of convertible notes of $220.4 million, purchase of royalty rights at fair value of $115.0 million, payment of dividends of $98.3 million, repayment of a portion of the March 2015 Term Loan of $75.0 million, purchase of notes receivable of $35.2 million, and payment of debt issuance costs related to the February 2018 Note issuance of $0.6 million, partially offset by proceeds from the March 2015 Term Loan of $100.0 million, proceeds from royalty rights of $43.4 million, repayment of notes receivables of $25.2 million, sale of investments of $1.9 million, and cash generated by operating activities of $301.5 million.

Recent Developments

In December 2015, Lion Buyer, a wholly owned subsidiary of ALPHAEON assumed $42.0 million in loans as part of the borrowings under PDL’s prior credit agreement with LENSAR and changed its name to LENSAR, LLC in connection with ALPHAEON’s acquisition of substantially all of the assets of LENSAR. In addition, ALPHAEON issued 1.7 million shares of its Class A common stock to PDL for an estimated fair value of $3.84 per share.

In December 2015 and January 2016, PDL and Direct Flow Medical modified the existing credit agreement. PDL funded an additional $5.0 million to Direct Flow Medical in the form of a short-term secured promissory note that we expect will be converted into a loan under the credit agreement with substantially the same interest and payment terms as the existing loans.
PDL’s $100.0 million term loan entered into on March 20, 2015 with the Royalty Bank of Canada was repaid with the final principal payment of $25.0 million plus accrued interest paid on February 12, 2016.

On February 18, 2016, PDL was advised that Sanofi and kaléo will terminate their license and development agreement later this year. At that time, all U.S. and Canadian commercial and manufacturing rights to Auvi-Q will be returned to kaléo, and they intend to evaluate the timing and options for bringing Auvi-Q back to the market. PDL entered into a secured note purchase agreement with Accel 300, a wholly-owned subsidiary of kaléo, which as of December 31, 2015, had a principal balance of $144.8 million due to PDL. An interest reserve account previously set up as part of the note agreement will substantially cover interest payments due to PDL through the end of the second quarter of 2016, and kaléo has indicated that it intends to make payments due to PDL under the note agreement until Auvi-Q is returned to the market.

2016 Dividends
On January 26, 2016, our board of directors declared a quarterly dividend to be paid to our stockholders in the first quarter of 2016 of $0.05 per share of common stock, payable on March 11, 2016 to stockholders of record on March 4, 2016, the record date of the dividend payment. At the same time our board of directors elected to announce its future dividend plans on a quarter by quarter basis, rather than for the full year as was the previous practice, to allow greater flexibility and focus on long term growth. Our board of directors evaluates the financial condition of the Company and considers the economic outlook, profitability, corporate cash flow, the Company’s liquidity needs and the health and stability of credit markets when determining the dividend.

On March 31, 2016 Following its announcement on 22 February 2016, Fastnet reported that it published an Admission Document detailing its conditional agreement to acquire the entire issued share capital of Amryt Pharmaceuticals DAC ("Amryt") for a consideration of £29.6 million to be satisfied by the issue of the Consideration Shares, (the "Acquisition"). The Company is also proposing to raise £10.0 million (before expenses) through a conditional placing of 41,673,402 New Ordinary Shares at the placing price of 24 pence per new Ordinary Share (equivalent to 3 pence per share before the Capital Reorganisation) and the issue of Placing Warrants on the basis of one Placing Warrant for every two Placing Shares subscribed.

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Joe Wiley, Proposed CEO of Amryt Pharma plc, commented:

"Today’s announcement is an important step towards realising the Company’s vision of building a specialty pharmaceutical company focused on best in class treatments for Orphan Diseases. We are focused on building a portfolio of differentiated medicines, in therapeutic areas where there is large unmet medical need and which offer significant commercial potential.

"Importantly, the £10 million in new funds will enable us to accelerate the development of Episalvan as a treatment for epidermolysis bullosa, a rare, debilitating, genetic skin disorder and orphan condition that typically affects young children and for which there is currently no approved therapy. We believe the recent European approval of Episalvan for the treatment of Partial Thickness Wounds in adults and a successfully completed phase IIa trial in epidermolysis bullosa itself meaningfully de-risks the probability of approval in this indication."

The Acquisition constitutes a reverse takeover in accordance with Rule 14 of the AIM Rules for Companies and Rule 14 of the ESM Rules for Companies. Fastnet is seeking Shareholder approval for the Proposals at the General Meeting. Subject to approval of the Proposals, the Company will change its name to Amryt Pharma plc and begin trading under the new tickers "AMYT" (AIM) and "AYP" (ESM).

Amryt was incorporated in August 2015 as a platform to acquire, build, develop and subsequently monetise a pipeline of patent protected, commercially attractive, proprietary drug candidates targeting best in class performance chosen to meet the Orphan Drug Designation criteria. Where appropriate, the Enlarged Group will commercialise the drugs it successfully develops through its own salesforce. In line with this strategy, Amryt has entered into agreements, conditional, inter alia, on Admission to acquire both Birken AG ("Birken") and SomPharmaceuticals ("Som"). Birken is a revenue generating pharmaceutical development and manufacturing company based in Germany that has developed a recently approved drug for partial thickness wounds and promising potential orphan drug candidate for epidermolysis bullosa ("EB"). Som is a Swiss/US based biopharmaceutical company focused on developing novel somatostatin analogue peptide medicines for patients with rare neuroendocrine diseases with high unmet need, principally focused on additional orphan drug candidates to address acromegaly and Cushing’s disease.

The New Board intends to use the net proceeds of the Placing to initiate a Phase III clinical trial of Episalvan with a view to obtaining a label extension for Episalvan to include approval for the treatment of EB in Europe and seek regulatory approval in the US.

Highlights

The New Board believes that following completion of the Acquisition, the Enlarged Group will have the following key strengths:

An approved drug – Birken’s lead drug, Episalvan, is a potential treatment for the orphan condition epidermolysis bullosa ("EB"), already approved in Europe as a treatment in adults for accelerated healing of partial thickness wounds ("PTWs") following three successful phase III studies.

· EB is a rare and distressing genetic skin disorder typically affecting young children, where there is currently no approved treatment.

o EB leads to mechanical fragility of skin, characterised by the presence of recurrent PTWs and blisters as a result of mutations in structural proteins.

· Episalvan has been awarded Orphan Drug Designation ("ODD") in the US and EU for EB.

· The drug has successfully completed a Phase IIa study in ten EB patients (data from 12 wounds).

o Episalvan demonstrated significantly faster healing over 14 days of treatment for recent wounds and 28 days of treatment for chronic wounds compared with standard of care therapy.

· The global EB market is estimated to be worth approximately US$1.5 billion per annum.

· The drug received formal marketing approval from the European Commission on 14 January 2016 for the treatment in adults for accelerated healing of PTWs.

o PTWs involve loss of the epidermis and basement layers of skin extending into the dermis layer below.

o Episalvan effectively represents a new category of advanced wound care. management in PTWs and is targeting a market which the New Board assesses to be worth in excess of €150 million.

· The Company intends to seek approval for Episalvan in EB in Europe and the US and will embark on a phase III study in H2 2016 in this indication.

A highly experienced management team – The New Board and senior management is comprised of experienced industry participants including:

· Harry Stratford, Chairman, is the founder of Shire plc, now a FTSE 100 biopharmaceutical company, and ProStrakan Group plc

· Joseph Wiley, CEO, has over 20 years’ experience in healthcare investment and pharmaceutical operational roles

· Rory Nealon, CFO and COO, has spent the last 13 years as both CFO and then COO of Trinity Biotech PLC, a NASDAQ listed company

· Michele Bellandi, CCO, is the former Head of Commercial Europe for Shire AG International and has held senior marketing roles at Serono and Eli Lilly

· Ray Stafford, a Non-Executive Director, previously EVP of Global Marketing for Forest Laboratories which was listed on NYSE prior to being acquired for approximately US$28 billion

· James Culverwell, a Non-Executive Director, previously head of European pharmaceutical equity research at Merrill Lynch in London until 2005.

An attractive potential opportunity in Acromegaly/Cushing’s disease

· The Company estimates the Acromegaly and Cushing’s disease markets to be in excess of US$1.15 billion per annum in aggregate

A business model that offers an attractive risk/reward profile

· Recent approval of Episalvan together with Birken’s existing Imlan product line should appreciably lower the risk profile of the Company, whereas the opportunity in the EB and Acromegaly/Cushing’s disease markets offers significant upside potential

· The risks associated with obtaining regulatory approval in EB have been reduced following the European approval of Episalvan in PTWs in adults in Europe

Orphan Drug market represents a significant opportunity

· Worldwide orphan drug sales are forecast to total US$176bn (CAGR 2014 – 2020:+10.5%)

· Orphan Drugs are set to be 19.1% of worldwide prescription sales by 2020

· Currently there are 7,000 orphan diseases with 1 in 10 of the world’s population suffering from an orphan disease

Use of proceeds from the transaction include:

· Satisfying certain of the milestone payments now due as payable under the Birken SPA

· Fund the clinical trial costs associated with seeking approval of Epislavan as a treatment for EB
· Satisfy certain liabilities of Som under the Som SPAs; and

· For general working capital purposes for the Enlarged Group.

Unless the context otherwise requires, defined terms shall have the meaning ascribed to them in the Admission Document. The Admission Document is available on the Company’s website www.fastnetequity.com

On February 22, 2016 PDL BioPharma, Inc. (PDL) (NASDAQ: PDLI) reported financial results for the fourth quarter and twelve months ended December 31, 2015 (Filing, 8-K, PDL BioPharma, FEB 22, 2016, View Source [SID:1234509130]).

Total revenues in 2015 increased two percent to $590.4 million from $581.2 million in 2014. Revenues for the year ended December 31, 2015 included $485.2 million in royalties from PDL’s licensees to the Queen et al. patents, $68.4 million in net royalty payments from acquired royalty rights and a change in fair value of the royalty rights assets, which included approximately $43.4 million in net cash royalty payments, $36.2 million in interest revenue from notes receivable debt financings to late-stage healthcare companies, and $0.7 million in realized gains from the sale of PDL’s investment in AxoGen Inc. common stock. During the years ended December 31, 2015 and 2014, our Queen et al. royalty revenues consisted of royalties and maintenance fees earned on sales of products under license agreements associated with our Queen et al. patents. During the years ended December 31, 2015 and 2014, royalty rights – change in fair value consisted of revenues associated with the change in estimated fair value of our royalty right assets, primarily Depomed, Inc., The Regents of the University of Michigan, Viscogliosi Brothers, LLC, ARIAD Pharmaceuticals Inc. and AcelRx Pharmaceuticals, Inc. The full year 2015 revenue growth over the full year 2014 is driven by increased sales of Perjeta, Xolair, and Kadcyla by PDL’s licensees, an increase in the estimated fair value of the acquired royalty rights from the Company’s purchase of Depomed’s diabetes-related royalties, as well as a foreign exchange gain and lower rebate paid to Novartis AG for Lucentis, partially offset by decreased interest revenues due to the early payoff of the AxoGen and Durata Therapeutics, Inc. notes receivables.

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Total revenues for the fourth quarter of 2015 increased 52 percent, to $178.1 million from $117.1 million in the fourth quarter of 2014. Revenues for the fourth quarter of 2015 included $121.2 million in royalty payments from PDL’s licensees to the Queen et al. patents, $49.1 million in net royalty payments from acquired royalty rights and a change in fair value of the royalty rights assets, which included approximately $34.4 million in net cash royalty payments, $7.6 million in interest revenue from notes receivable debt financings to late-stage healthcare companies, and $0.1 million in realized gains from the sale of PDL’s investment in AxoGen common stock. The fourth quarter of 2015 revenue growth over the fourth quarter of 2014 is driven by the change in estimated fair value of our royalty right assets, primarily Depomed, Inc.

Operating expenses in 2015 were $40.1 million, compared with $34.9 million in 2014. Operating expenses in the fourth quarter of 2014 were $16.5 million, compared with $17.7 million in 2014. The increase in operating expenses for the year ended December 31, 2015, when compared to the year ended December 31, 2014, was a result of total restructuring costs of $7.9 million in connection with the LENSAR notes receivable extinguishment, which is comprised of a loss on extinguishment of notes receivable of $4.0 million primarily related to a lower estimated fair value of the ALPHAEON Class A common stock, and additional general and administrative expenses of $3.9 million for closing and legal fees related to the LENSAR notes receivable restructuring, and other legal expenses mostly related to $1.2 million in funding the ongoing operation management of Wellstat Diagnostics, partially offset by a decrease in professional services from asset acquisition expenses. The decrease in operating expenses for the quarter ended December 31, 2015, when compared to the quarter ended December 31, 2014, was a result of a decrease in professional services from asset acquisition expenses and a decrease in compensation related expenses,

partially offset by the LENSAR restructuring loss and other closing fees, and an increase for legal expenses mostly related to Wellstat ongoing operation management.

Net income in 2015 was $332.8 million, or $2.03 per diluted share as compared with net income in 2014 of $322.2 million, or $1.86 per diluted share. Net income for the fourth quarter of 2015 was $100.6 million, or $0.61 per diluted share, as compared with net income of $55.1 million in the same period of 2014, or $0.32 per diluted share.

Net cash provided by operating activities in 2015 was $301.5 million, compared with $292.3 million in the same period in 2014. PDL had cash, cash equivalents and short-term investments of $220.4 million and $293.7 million at December 31, 2015 and 2014, respectively. The decrease was primarily attributable to the extinguishment of convertible notes of $220.4 million, purchase of royalty rights at fair value of $115.0 million, payment of dividends of $98.3 million, repayment of a portion of the March 2015 Term Loan of $75.0 million, purchase of notes receivable of $35.2 million, and payment of debt issuance costs related to the February 2018 Note issuance of $0.6 million, partially offset by proceeds from the March 2015 Term Loan of $100.0 million, proceeds from royalty rights of $43.4 million, repayment of notes receivables of $25.2 million, sale of investments of $1.9 million, and cash generated by operating activities of $301.5 million.

Recent Developments

In December 2015, Lion Buyer, a wholly owned subsidiary of ALPHAEON assumed $42.0 million in loans as part of the borrowings under PDL’s prior credit agreement with LENSAR and changed its name to LENSAR, LLC in connection with ALPHAEON’s acquisition of substantially all of the assets of LENSAR. In addition, ALPHAEON issued 1.7 million shares of its Class A common stock to PDL for an estimated fair value of $3.84 per share.

In December 2015 and January 2016, PDL and Direct Flow Medical modified the existing credit agreement. PDL funded an additional $5.0 million to Direct Flow Medical in the form of a short-term secured promissory note that we expect will be converted into a loan under the credit agreement with substantially the same interest and payment terms as the existing loans.

PDL’s $100.0 million term loan entered into on March 20, 2015 with the Royalty Bank of Canada was repaid with the final principal payment of $25.0 million plus accrued interest paid on February 12, 2016.

On February 18, 2016, PDL was advised that Sanofi and kaléo will terminate their license and development agreement later this year. At that time, all U.S. and Canadian commercial and manufacturing rights to Auvi-Q will be returned to kaléo, and they intend to evaluate the timing and options for bringing Auvi-Q back to the market. PDL entered into a secured note purchase agreement with Accel 300, a wholly-owned subsidiary of kaléo, which as of December 31, 2015, had a principal balance of $144.8 million due to PDL. An interest reserve account previously set up as part of the note agreement will substantially cover interest payments due to PDL through the end of the second quarter of 2016, and kaléo has indicated that it intends to make payments due to PDL under the note agreement until Auvi-Q is returned to the market.

2016 Dividends
On January 26, 2016, our board of directors declared a quarterly dividend to be paid to our stockholders in the first quarter of 2016 of $0.05 per share of common stock, payable on March 11, 2016 to stockholders of record on March 4, 2016, the record date of the dividend payment. At the same time our board of directors elected to announce its future dividend plans on a quarter by quarter basis, rather than for the full year as was the previous practice, to allow greater flexibility and focus on long term growth. Our board of directors evaluates the financial condition of the Company and considers the economic outlook, profitability, corporate cash flow, the Company’s liquidity needs and the health and stability of credit markets when determining the dividend.

On February 20, 2016 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported new clinical data on CDX-301 (recombinant human Flt3 ligand), a potent hematopoietic cytokine that uniquely expands dendritic cells and hematopoietic stem cells (Press release, Celldex Therapeutics, FEB 20, 2016, View Source [SID:1234509111]). An open label, pilot study of CDX-301, alone and in combination with Mozobil (plerixafor), in sibling-matched donors for allogeneic hematopoietic stem cell transplantation (HSCT) recipients who have certain hematologic malignancies is currently enrolling donor/patient pairs. Early data were presented in a poster entitled "Preliminary Safety and Efficacy Data using CDX-301 (Flt3 ligand) as a Sole Agent to Mobilize Hematopoietic Cells Prior to HLA-matched Sibling Donor Transplantation" at the 2016 BMT Tandem Meeting, the annual meeting of the American Society for Blood and Marrow Transplantation (ASBMT). The poster is available on the "Publications" page of the "Science" section of the Celldex website.

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Three donor/patient pairs showed that CDX-301 given as a single agent for 5 days was well tolerated and effective at mobilizing hematopoietic stem cells in healthy donors. The stem cell graft contained notable increases in naïve lymphocytes and plasmacytoid dendritic cells compared to administration of G-CSF (granulocyte colony-stimulating factor) and is consistent with preclinical data suggesting a possible better outcome for recipients. Notably, no donors required rescue with either G-CSF or Mozobil in this arm of the study, and none experienced any grade 3 or 4 adverse events. Recipients experienced successful engraftment in an expected time frame. Additional donor/patient pairs are being accrued to a second, planned cohort in order to assess the potential synergies and feasibility of combining CDX-301 with Mozobil in this setting.

"From these data and preclinical studies, CDX-301 appears to be an effective, targeted approach to mobilization comparable to G-CSF. With a relatively short course of treatment, we are observing specificity for mobilized stem cells and a lack of toxicity, instead of broad cellular mobilization and side effects," said Steven Devine, M.D., Professor of Internal Medicine, Division of Hematology, Department of Internal Medicine, and Program Director, Blood and Marrow Transplant Program at The Ohio State Comprehensive Cancer Center.

"CDX-301 shows a favorable safety profile and effectively mobilizes early stem cells when used alone, and we expect even greater yields in the next cohort where we combine with Mozobil," said Thomas Davis, M.D., Executive Vice President and Chief Medical Officer of Celldex Therapeutics . "CDX-301 could potentially provide good engraftment, less graft-versus-host disease and mitigated side effects, which would be a breakthrough for these patients undergoing HSCT. We are also looking forward to receiving data from investigators who are using CDX-301 in other drug combination studies designed to assess its potential in immunotherapy for cancer and other indications."

In addition, CDX-301 has shown impressive results in models of cancer, infectious diseases, inflammatory/autoimmune diseases and immune suppression. Celldex believes CDX-301 may hold significant opportunity for synergistic development in combination with other proprietary molecules in the Company’s portfolio and in external development. CDX-301 is in clinical development for cancers in combination with vaccines, adjuvants, and other treatments that result in release of tumor antigens to enhance tumor immunogenicity.

On February 19, 2016, the U. S. Food and Drug Administration approved palbociclib (IBRANCE Capsules, Pfizer, Inc.) in combination with fulvestrant for the treatment of women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy.
In February 2015, FDA granted accelerated approval for palbociclib in combination with letrozole for the treatment of HR-positive, HER2-negative advanced breast cancer as initial endocrine based therapy in postmenopausal women.

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Today’s approval is based on the demonstration of an improvement in progression – free survival (PFS) in an international, randomized, double-blind, parallel group, multicenter study comparing palbociclib plus fulvestrant to placebo plus fulvestrant. Women enrolled had HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression on or after prior adjuvant or metastatic endocrine therapy.

A total of 521 pre- and postmenopausal women were randomized (2:1) to either palbociclib plus fulvestrant or placebo plus fulvestrant until disease progression or unacceptable toxicity. Palbociclib was administered orally at a dose of 125 mg daily for 21 consecutive days followed by 7 days off treatment. Fulvestrant was administered intramuscularly at a dose of 500 mg on days 1, 15, 29 and once monthly thereafter. Pre- or perimenopausal women were enrolled in the study and received the LHRH agonist, goserelin, for at least 4 weeks prior to and for the study’s duration.

Among the 521 patients, 80% were postmenopausal, all patients had received prior systemic therapy, and 75% had received a previous chemotherapy regimen. Twenty-five percent had not received prior therapy for metastatic disease, 60% had visceral metastases, and 23% had bone only disease.

The major efficacy outcome measure was investigator-assessed PFS evaluated according to RECIST V1.1. The study demonstrated an improvement in PFS with a hazard ratio of 0.46 (95% CI: 0.36, 0.59; p<0.0001). The median PFS was 9.5 versus 4.6 months for patients treated in the palbociclib plus fulvestrant and placebo plus fulvestrant arms, respectively.

Safety data was evaluated in 345 patients who received palbociclib plus fulvestrant. The most common (greater than or equal to 10%) of grade 1-4 adverse reactions were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, headache, diarrhea, thrombocytopenia, constipation, vomiting, alopecia, rash, decreased appetite, and pyrexia. The most common (greater than or equal to 5%) grade 3-4 adverse reactions were neutropenia (66%) and leukopenia (31%).

The most frequently reported serious adverse reactions in patients receiving palbociclib plus fulvestrant were infections, pyrexia, neutropenia, and pulmonary embolism). Dose reductions due to an adverse reaction of any grade occurred in 36% of patients and permanent discontinuation associated with an adverse reaction occurred in 6% of patients.

The recommended dose and schedule of palbociclib is 125 mg daily for 21 consecutive days followed by 7 days off treatment in combination with fulvestrant treatment. The dose and schedule of fulvestrant is 500 mg intramuscularly on days 1, 15, 29 and once monthly thereafter.

Palbociclib is being approved prior to the Prescription Drug User Fee Act (PDUFA) goal date of April 15, 2016. This application was granted Priority Review and Breakthrough Therapy Designation. A description of these expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at: View Source

Full prescribing information is available at:
View Source

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at View Source, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).