Please Note: Blog posts are not selected, edited or screened by Seeking Alpha editors.

Halozyme To Launch PegpH20 As New Treatment For Pancreatic Cancer- Confirms Recent 150 Patient Enrollment Addition In Phase 3

Summary

Halozyme's Double Blind Phase 3 Registration Trial is 2 years old.

A slowed event rate- requiring 1/3 more patients- 1:3 controls- was declared on Jan 8, 2018.

Primary Completion Date is October 2018.

HALO placed an advertisement for an Executive Marketing Director for the US launch of PegpH20 on Feb 9, 2018.

There has been no published improvement in metastatic pancreatic cancer Progression Free Survival and Overall Survival since Folfirinox was approved for this diagnosis in 2011- 6.4 month PFS 11.1 mo OS.

Halozyme is 2 years into a Double Blind Phase 3 Registration Trial with a slowed event rate requiring 1/3 more patients. Primary Completion Date is October 2018.

Scripps and UCSF are running open label PegpH20 trials in Pancreatic Cancer.

Based on Above data, Halo has recently Advertised a position for an Executive Marketing Director to launch pegpH20 (HALO has no other new unpartnered products becoming commercially available).

This add was placed on Halozyme Careers site on Feb 9, 2018:

 

Executive Director, US Marketing

POSITION SUMMARY:

The Executive Director, US Marketing is responsible for the development, implementation, management and execution of an effective US Marketing Plan designed to result in strong adoption and prescription of the launch product. This individual will provide marketing strategy, functional expertise, and strong leadership of the US Marketing Organization, which will require build-out in 2018 & 2019.   The Executive Director, US Marketing will work closely with the Heads of Sales, Market Access & Commercial Operations to ensure the tightly integrated Commercial Launch Plans required to maximize opportunity. 
 

The position can be located in San Diego or San Francisco.

ESSENTIAL FUNCTIONS AND RESPONSIBILITIES:

These may include, but are not limited to:

·       Hire a talented marketing team 

·       Direct the day-to-day activities of the Marketing Strategy, Marketing Promotions & Key Customer Marketing sub-teams. 

·       Generate and leveraging a range of marketplace insights to identify market-driving strategies and executional plans to achieve maximal brand uptake  Assuring attainment of all quarterly & annual US Performance Metrics and Launch Key Performance Indicators

·       Create a promotional materials that support and deliver on brand’s strategy and goals

·       Ensure insights are gained from the nation’s top clinical experts

·       Identifying and asserting appropriate training of clinical experts to engage in speaker events

·       Collaborate with the Sales & Training Leadership Team to monitor performance, ensure message pull through and uncover opportunities / issues in execution

·       Lead the US Marketing Organization’s efforts in key business planning process, including: Strategic Brand Planning, Launch Planning, Tactical Planning, Competitive Readiness, & Quarterly Performance Reviews 

·       Ensure all marketing communications are clear, coordinated, compliant and consistent with well-defined brand objectives & priorities

·       Collaborate with Commercial Analytics Team to generate commercial assessments for future indications, pipeline products and BD opportunities

·       Respond to urgent market and customer priorities as they occur and mobilizing the appropriate marketing resources to meet the need

·       Foster a productive relationships throughout the entire organization Identifying areas for process and systems innovation and implements change that will enhance the overall effectiveness & efficiency of the commercial organization 

·       Advocate a solutions oriented culture of teamwork, accountability, strong performance and excellence in competency and character

·       Lead, manage, coach and develop others to ensure successor readiness & professional development within the marketing organization

·       Exhibit knowledge of, and adhere to, all applicable healthcare laws and regulations, industry practices and Halozyme policies related to product marketing and promotion.

EDUCATION, EXPERIENCE, KNOWLEDGE, SKILLS AND ABILITIES:

·       Minimum of a Bachelor's degree in marketing, health care, business administration or related; Master’s and/or Doctorate degrees preferred with at least 12 years of progressively responsible experience within marketing and sales related functions (an equivalent combination of relative experience and education may be considered)

·       At least 3 of the following a) launch of oncology products, b) strategic marketing c) marketing promotions d) customer facing roles (key customer marketing or sales)

·       Significant commercial experience from biopharma, and motivated by the prospect of growth in an early stage entrepreneurial company setting

·       Skills required to build effective relationships to manage alliances and collaborations with vendors, suppliers and partners

·       Adept communications skills for dealing with diverse internal and external audiences

·       Proven track record of recruiting and developing high caliber individuals and building teams that communicate well and execute efficiently

·       Ability to think clearly and critically, articulate a vision, and inspire others to follow

·       Ability to make dispassionate and objective decisions based on hard data as well as soft data

·       Experience to know when available data is sufficient to make decisions with demonstrated good judgment, ethical behavior, decisiveness, strategic vision, and exceptional interpersonal skills

·       Thinks strategically at the executive level, implements change, incorporates innovation and implements strategies throughout all levels of the organization

·       Ability to build and sustain trusted relationships both internally and externally

·       Strength in analysis, critical decision making and bottom line accountability

INTERNAL AND EXTERNAL RELATIONSHIPS:

·       Active member of the Senior Commercial Leadership Team and other senior-level, cross functional teams across the organization.

---------------------------------------------------------------------------

The story behind  the proposed launch of pegpH20 dates back to Aug 12, 2010 when Halozyme announced the issuance of U.S. Patent No. 7,767,429 claiming its proprietary recombinant human hyaluronidase enzyme platform (rHuPH20) and its PEGylated variants- for which HALO pays royalties to Nektar. This pegylation of rhupH20 allows the IV delivery of recombinant human hyaluronidase. There are two main purposes for this delivery. The more well known one is the reduction of high molecular weight from the solid tumor microenvironment, thereby reducing intratumor pressure, resulting in the decompression of blood vessels, which can then deliver more chemo and immunotherapy- be it checkpoint inhibitor or CAR-T- to the tumor per dose.

The second purpose refers back to the body's natural defense against  autoimmune disease. The presence of High Molecular weight Hylauronan in the TME in greater proportion than Low Molecular weight Hyaluronan induces the major Hyaluronan surface receptor on T cells to stimulate T regulatory cells, trurning down the activity of T effector and memory cells. This is how autoimmunity is controlled. This defense also interferes with Immuno-Oncologic treatment of solid cancer. It is a leading explanation for the difference between Complete responses to CAR-T in low Hylauronan Blood cancers and poor responses in Solid cancers. The alteration in the ratio of High to Low Molecular weight hyaluronan toward low by PegpH20, induces the turning off of T regs, the turning on of T effectors and better trafficking of I/O therapies into dense solid tumor. Manuel Hidalgo,

  • Professor, Medicine, Harvard Medical School
  • Chief, Hematology Oncology, Beth Israel Deaconess Medical Center
  • Director, Rosenberg Clinical Cancer Center, Beth Israel Deaconess Medical Center
  • Co-Director, Pancreatic Cancer Research Program, Beth Israel Deaconess Medical Center

 has recently stated that "Pegylated hyaluronidase, may, at the end of the day, make the tumor hot for immunotherapy" 

Clinical Research in the Treatment of Pancreas Cancer

In clinical trials, PegpH20 has the leading Progression Free Survivals of 7, 8, and 9.2 months of any combination Pancreatic Cancer combinations- all with Gemcytabine and Abraxane- the standard of care. In Phase 2 results as always were best in patients whose tumors were high in Hyaluronan- a measure now made with a proprietary Roche Ventana Biomarker: PFS was significantly improved with PAG treatment overall (hazard ratio [HR], 0.73; 95% CI, 0.53 to 1.00; P = .049) and for patients with HA-high tumors (HR, 0.51; 95% CI, 0.26 to 1.00; P = .048). In patients with HA-high tumors (PAG v AG), the objective response rate was 45% versus 31% with low Hyaluronan tumors,  and median overall survival was 11.5 versus 8.5 months (HR, 0.96; 95% CI, 0.57 to 1.61). Based on this data, the FDA has allowed Halozyme what is an unusual first Primary Endpoint in a study of metastatic cancer- Progression free Survival. They have also guided that they will accept an New Drug Application with Positive Progression Free Survival and "supportive" Overall survival, in an effort to accelerate a much needed therapy that may meet the most dire of unmet needs in oncology. 

Against this backdrop, SWOG ran S1313- a Folfirinox-PegpH20 trial. It did not screen for High Hyaluronan status. The 5 drug (4+1) combination proved too toxic at the usual 3 microgram per kg twice a week loading dose- tapered to once a week maintenance. So SWOG decided to administer sub-therapeutic every other week dosing- 25-50% of standard pegpH20 dose- which of course lead to a halt for futility, especially since the small (69 patient) control group was the healthiest Folfirinox cohort in history - with an Overall Survival 37% better than the standard Conroy Folfirinox study published in the NEJM.

At the same ASCO GI meeting where SWOG presented this yesr, Eileen O'Reilly and her group at Memorial Sloane Kettering also presented interim data from an open label trial, "Study of Gemcytabine, Nab-paclitaxel, PEGPH20 and Rivaroxaban for Advanced Pancreatic Adenocarcinoma." NCT02921022 In a mixed Stage 3,4 population they showed shows an 86% Disease Control rate with 8.6mo PFS and 57% ORR- small study but corroborates P2- 9.2 mo in High HA pts. However, like SWOG, O'Reilly didn't screen for Hyaluranon. But she did use the full therapeutic dose of pegpH20, as outlined above. That is very likely the difference. 

On Jan 8, 2018, 23 months into Phase 3 PegpH20, Gemcytabine, And Abraxane in High hyaluronan (as Identified by Ventana in the first Biomarker PDA study of its kind) Halozyme announced on Clinicaltrials.gov that the Data Monitoring Committee allowed an additional 33% of patients be enrolled in P3 with the usual 2:1 Treatment;control distribution. During the Q3 2017 Earnings meeting held on November 7, 2017- he following exchange took place: 

Jim Birchenough

"Two questions if I may and I apologies, if I should know the answer to one or both of them. But certainly 301 trial is originally listed as 420 patients. I think you have a range on the side of 420 to 570 and that the PFS analysis will be done when you expect 500 patients to be enrolled. Can you just enlighten me as to what the gating factor is in terms of the final enrollment?

Dr. Helen Torley

Nick, when we started the study, we originally mentioned the fact that this is the study that we go from 420 to 570 patients, if recall, because of the adaptive design. With the first time endpoint, the first primary endpoint being look at being progression-free survival, what we now see based on the accumulation of data will be giving the study is that we estimate will be 500 patients by the time we get to that first primary analysis. We choose on the PFS, we distribute by a target number of PFS event. I guess what we have information to update you all with regard to.

Jim Birchenough

Basically, the event rate is a little slower than it was anticipated."

Jim Birchenough is in my view the Dean of Halozyme Analysts. He was certainly the most accurate an the eventual outcome of PegpH20 trials after its halt prior to Low Molecular Weight Heparin use. so he recognizes the "slower event rate". 

Well, what is the "event' either death or progression- defined under RECIST as a growth of 20% in the target lesion. So if this rate is slowed tht could be a result in PegpH20 working in the treatment group or of an unusual response in the control group- as in S1313. Recall S1313 was halted for futility by the DMC. I can imagine no circumstance in which the unblinded DMC statistician would allow 100 more of the 150 additionally enrolled to receive PegpH20 if the control group was doing better than the treatment group- a sign of futility. More likely PegpH20 is slowing progression which is falling short of the target to report and another 50 control patients will, unfortunately do what Gemcytabine-Abraxane patients with PDA do- progress in 5.5 months.

That brings us to the primary completion date of Halozyme P3: October 2018. But as we said earlier, the FDA granted HALO 2 Primary Endpoints- PFS and OS- so does this mean only PFS will be done by then- 2 3/4 years after the trial was begun? "No, per Clinicaltrials.gov, the Primary Completion Date is the date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for ALL the primary outcome measures." So it is possible that we will very soon get a PFS reading from Halozyme Phase 3- perhaps at ASCO- while the Overall survival data is tabulated and Halozyme seeks a Marketing Professional to Launch PegpH20.

Disclosure: I am/we are long HALO MRK.