Global Blood Therapeutics (GBT) President and CEO Ted W. Love, MD

Pfizer has agreed to acquire Global Blood Therapeutics (GBT) for $5.4 billion cash, the companies said Monday, in a deal that continues the pharma giant’s spate of acquisitions made possible by the billions of dollars generated by its COVID-19 vaccine and antiviral drug.

Pfizer said the deal will complement and further enhance its 30-plus year heritage in rare hematology and reinforce its commitment to treating sickle cell disease (SCD), for which GBT has a marketed drug Oxbryta® (voxelotor) approved by the FDA in 2019.

That year, Pfizer acknowledged that a synthetic glycomimetic it licensed from GlycoMimetics, rivipansel, had failed a Phase III trial in patients with SCD who were hospitalized for a vaso-occlusive crisis (VOC) and required treatment with intravenous opioids. Soon after, Pfizer ended an up-to-$340 million ($15 million upfront) collaboration with GlycoMimetics launched in 2011.

Rivipansel wasn’t Pfizer’s only SCD candidate in recent years. In 2020, Pfizer quietly ended a Phase I trial of PF-04447943, only a year after publication of a preclinical study that the phosphodiesterase 9A inhibitor “demonstrated PK/PD effects suggestive of inhibiting pathways that may contribute to vaso-occlusion.” PF-04447943 has since been dropped from Pfizer’s pipeline.

Pfizer said GBT’s expertise, portfolio, and pipeline, holds potential to address the full spectrum of critical needs for the SCD community, which Pfizer has committed to engaging through the deal.

“We are excited to welcome GBT colleagues into Pfizer and to work together to transform the lives of patients, as we have long sought to address the needs of this underserved community,” Albert Bourla, Pfizer’s Chairman and CEO, said in a statement. “The deep market knowledge and scientific and clinical capabilities we have built over three decades in rare hematology will enable us to accelerate innovation for the sickle cell disease community and bring these treatments to patients as quickly as possible.”

The Wall Street Journal first reported Pfizer’s advanced talks to acquire GBT on Friday, about two weeks after a Bloomberg News report identified GBT as a potential takeover target, touching off a 41% jump on the company’s share price August 4, from $33.93 to $47.99.

Shares of GBT rose 4% to $66.64 in midday trading as of 12:54 p.m. ET.  Pfizer shares dipped 0.43% to $49.06 from $49.27.

51% Sales gain

Citing the acquisition announcement, GBT postponed its scheduled quarterly conference call with analysts, but did release second quarter results showing product sales of $71.55 million for Oxbryta, up nearly 51% from $47.555 million in Q2 2021.

The Q2 sales result fell in line with the forecast of analyst John Newman, PhD, CFA of Canaccord Genuity, who early Monday before the deal was announced raised his quarterly sales forecast for Oxbryta from $64 million to $71 million, citing strong pediatric uptake of the drug.

Global Blood Therapeutics President and CEO Ted W. Love, MD, said a crucial factor behind the successful development of Oxbryta was shifting the R&D focus from relieving pain, the traditional concern of sickle cell disease (SCD) drug developers, to improving the health of red blood cells. [Global Blood Therapeutics]
“We expect faster Oxbryta uptake in pediatric sickle cell disease patients vs adolescents or adults, as we believe parents and physicians see greater urgency to treat the disease in young children,” Newman wrote in a research note. “We also expect better compliance and adherence for younger patients overall.”

So far this year, Oxbryta has generated $126.71 million in product sales, up 46% from $86.598 million in the first half of 2021. Oxbryta racked up $194.749 million in product sales in 2021, up 57% from $123.803 million in 2020.

Pfizer said it plans to build on those sales by leveraging its global platform to accelerate distribution of Oxbryta to parts of the world most impacted by SCD. In addition to the U.S., Oxbryta is approved in the European Union, United Arab Emirates, Oman and Great Britain.

Speaking on GEN’s “Close to the Edge” video interview series last year, GBT President and CEO Ted W. Love, MD, complimented Pfizer as well as Moderna for their rapid development of COVID-19 vaccines [Pfizer partnered with BioNTech to develop COMIRNATY®] based on messenger RNA (mRNA).

“The application of that technology positioned Moderna and Pfizer to really do something that I think people would have thought unfathomable a few years ago. So I think the rate of acceleration of us being able to use novel technology, novel science, it’s accelerating.  And I think that’s going to continue, which is why I’m so excited and, quite frankly, proud of our industry,” Love said.

Pfizer’s successful development of COMIRNATY generated billions of dollars for the company—$36.781 billion in 2021 and $22.075 billion in the first six months of this year alone.

The company has since spent some of that money on an acquisition spree. Since the vaccine was emergency-authorized in 2020, Pfizer last year bolstered its oncology drug portfolio by acquiring Trillium Therapeutics for $2.26 billion.

In April, Pfizer shelled out up to $525 million for ReViral, a developer of antiviral therapeutics targeting respiratory syncytial virus (RSV). A month later, Pfizer bought Biohaven Pharmaceuticals for $11.6 billion cash, expanding its portfolio and pipeline with therapies for migraine led by the FDA-approved rimegepant (Nurtec® ODT).

“We’ve been very clear that our goal is to add $25 billion of risk adjusted revenue by 2030 and I think we are making very good progress against that,” Aamir Malik, Chief Business Innovation Officer, told analysts July 28 on the company’s quarterly earnings call. “This year you saw our transaction with ReViral and subsequently with Biohaven, which respectively we believe have the potential to add $1.5 billion and $6 billion in peak sales to our business, and this was on the back of a very active 2021

Looking beyond pain

On GEN’s “Close to the Edge,” Love said a crucial factor behind the successful development of Oxbryta was shifting the R&D focus from relieving pain, the traditional concern of SCD drug developers, to improving the health of red blood cells.

“We really needed to kind of flip how people were thinking from not just pain but, what is really going on in sickle cell disease? And we’ve been now trying to get people to understand that a disease that occurs on one protein that’s trapped inside your red cell is really killing the red cells first. It’s killing the red cell first,” Love said on “Close to the Edge.”

“I was very strident early on. We are not going to develop a drug focused on pain. We are going to focus on the fundamental basis of this disease, which is the hemoglobin polymerization that’s killing the red cell. And what we ultimately agreed to with the Food and Drug Administration is that the primary endpoint for our drug’s approval would be stopping the polymerization from killing the red cell,” Love added.

Oxbryta won accelerated FDA approval in November 2019 as a treatment for SCD in patients 12 years old and older. The FDA based its approval on positive clinical data Oxbryta generated in the Phase III HOPE (Hemoglobin Oxygen Affinity Modulation to Inhibit HbS PolymErization) trial (NCT03036813). Of 274 patients evaluated, more than 50% treated with Oxbryta achieved greater than 1 g/dL increase in hemoglobin, compared with 6.5% receiving placebo.

Oxbryta is indicated as an SCD treatment in patients ages 4 and up. The drug is also under clinical review in:

  • SCD patients 2-15 years of age, the focus of the Phase III HOPE-KIDS 2 trial (NCT04218084), a confirmatory study designed to measure the mean change in transcranial doppler (TCD) flow velocity, seeking to demonstrate a decrease in stroke risk. HOPE-KIDS 2 was initiated in December 2019 as a condition of the accelerated approval.
  • SCD pediatric patients up to 17 years of age, the focus of the Phase IIa HOPE-KIDS 1 trial (GBT440-007; NCT02850406), an open-label, single- and multiple-dose trial evaluating the safety, tolerability, pharmacokinetics and exploratory treatment effect of Oxbryta in pediatric patients as young as 6 months of age..
  • SCD patients 12 years of age and older, the focus of a planned Phase IV study set to evaluate daily physical activity in those patients.

Love has also defended Oxbryta’s $125,000/year list price, which GBT had pledged not to raise through this year, citing the drug’s efficacy against SCD and savings to SCD patients of over $700,000 in otherwise lost lifetime income due to the disease.

“If you go into a disease area where there’s nothing available, looking at the alternative price value of the alternative is a silly discussion. The alternative is to continue to let these patients suffer and die,” Love told investors attending the Biotechnology Innovation Organization (BIO) CEO & Investor Conference in New York in February 2020.

$3 Billion franchise

Also in GBT’s pipeline is inclacumab, a fully human monoclonal antibody targeting P-selectin which is under study in two Phase III trials as a potential quarterly treatment to reduce the frequency of painful vaso-occlusive crises (VOCs) and reduce hospital readmission rates due to VOCs.

GBT has an exclusive worldwide up-to-$127 million-plus licensing agreement with Roche for inclacumab inked in 2018 –$2 million paid upfront to Roche, up to $125 million tied to achieving development and commercialization milestones, plus tiered royalties. Inclacumab has established pharmacokinetic data, safety and tolerability in more than 500 patients.

GBT’s pipeline also includes GBT601 (formerly GBT021601), an oral, once-daily, next-generation sickle hemoglobin (HbS) polymerization inhibitor under study in Phase I and Phase II/III trials. The Phase I trial (NCT04983264) was completed in late 2021, then restarted in the second quarter of 2022 to evaluate a higher daily dose of GBT601 than previously studied, based on patient demand. In June, GBT announced the initiation of the Phase II portion of the Phase II/III trial (NCT05431088), with the primary outcome measure of the Phase II portion being the number of patients with a change from baseline in hemoglobin, or Hb, levels through Week 12.

GBT has presented positive Phase I proof-of-concept data for GBT601 at the American Society of Hematology’s ASH 2021 conference, held December 11-14 in Atlanta. GBT said the data has shown GBT601’s potential to improve clinical outcomes in people living with SCD, while reducing pill burden.

Both GBT601 and inclacumab have received FDA Orphan Drug and Rare Pediatric Disease designations.

GBT’s pipeline includes preclinical programs designed to treat SCD through HbF inducers (which could also potentially treat beta thalassemia), through a collaboration with Syros Pharmaceuticals; anti-sickling drugs; and inflammation and oxidative stress reduction.

If approved, GBT’s pipeline and Oxbryta could underpin an SCD franchise that according to the company could achieve combined worldwide peak sales of more than $3 billion.

Pfizer said it will acquire all outstanding shares of GBT for $68.50 per share in cash, a 7% premium to GBT’s closing share price of $63.84 on Friday. The deal’s total enterprise value of approximately $5.4 billion includes debt and is net of cash acquired.

Pfizer said it will buy GBT using cash on hand. The company reported $2.47 billion in cash and cash equivalents as of April 3; Pfizer has yet to disclose its second quarter balance sheets.

The boards of both companies have unanimously approved the transaction, which is subject to customary closing conditions, including receipt of regulatory approvals and approval by GBT’s stockholders.

“Pfizer will broaden and amplify our impact for patients and further propel much-needed innovation and resources for the care of people with sickle cell disease and other rare diseases, including populations in limited-resource countries,” Love said Monday in a statement. “We look forward to working together with Pfizer to serve our communities and advance our shared goal of improving health equity and expanding access to life-changing treatments to create a healthier future for all.”

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